Dihydroartemisinin induces ferroptosis of hepatocellular carcinoma via inhibiting ATF4-xCT pathway.

Management of hepatocellular carcinoma (HCC) remains challenging due to population growth, frequent recurrence and drug resistance. Targeting of genes involved with the ferroptosis is a promising alternative treatment strategy for HCC. The present study aimed to investigate the effect of dihydroartemisinin (DHA) against HCC and explore the underlying mechanisms. The effects of DHA on induction of ferroptosis were investigated with the measurement of malondialdehyde concentrations, oxidised C11 BODIPY 581/591 staining, as well as subcutaneous xenograft experiments. Activated transcription factor 4 (ATF4) and solute carrier family 7 member 11 (SLC7A11 or xCT) were overexpressed with lentiviruses to verify the target of DHA. Here, we confirmed the anticancer effect of DHA in inducing ferroptosis is related to ATF4. High expression of ATF4 is related to worse clinicopathological prognosis of HCC. Mechanistically, DHA inhibited the expression of ATF4, thereby promoting lipid peroxidation and ferroptosis of HCC cells. Overexpression of ATF4 rescued DHA-induced ferroptosis. Moreover, ATF4 could directly bound to the SLC7A11 promoter and increase its transcription. In addition, DHA enhances the chemosensitivity of sorafenib on HCC in vivo and in vitro. These findings confirm that DHA induces ferroptosis of HCC via inhibiting ATF4-xCT pathway, thereby providing new drug options for the treatment of HCC.

Microfluidic Device-Based In Vivo Detection of PD-L1-Positive Small Extracellular Vesicles and Its Application for Tumor Monitoring.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+ sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1+ sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1+ sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+ sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+ sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+ sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1+ sEVs, contributing to the clinical diagnosis and treatment of tumor.

Engineering yeasts to Co-utilize methanol or formate coupled with CO2 fixation.

The development of synthetic microorganisms that could use one-carbon compounds, such as carbon dioxide, methanol, or formate, has received considerable interest. In this study, we engineered Pichia pastoris and Saccharomyces cerevisiae to both synthetic methylotrophy and formatotrophy, enabling them to co-utilize methanol or formate with CO2 fixation through a synthetic C1-compound assimilation pathway (MFORG pathway). This pathway consisted of a methanol-formate oxidation module and the reductive glycine pathway. We first assembled the MFORG pathway in P. pastoris using endogenous enzymes, followed by blocking the native methanol assimilation pathway, modularly engineering genes of MFORG pathway, and compartmentalizing the methanol oxidation module. These modifications successfully enabled the methylotrophic yeast P. pastoris to utilize both methanol and formate. We then introduced the MFORG pathway from P. pastoris into the model yeast S. cerevisiae, establishing the synthetic methylotrophy and formatotrophy in this organism. The resulting strain could also successfully utilize both methanol and formate with consumption rates of 20 mg/L/h and 36.5 mg/L/h, respectively. The ability of the engineered P. pastoris and S. cerevisiae to co-assimilate CO2 with methanol or formate through the MFORG pathway was also confirmed by 13C-tracer analysis. Finally, production of 5-aminolevulinic acid and lactic acid by co-assimilating methanol and CO2 was demonstrated in the engineered P. pastoris and S. cerevisiae. This work indicates the potential of the MFORG pathway in developing different hosts to use various one-carbon compounds for chemical production.

Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach.

Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N = 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N = 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes.

Investigation of the mutual crosstalk between ER stress and PI3K/AKT/mTOR signaling pathway in iron overload-induced liver injury in chicks.

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway.

Anterior chamber and angle characteristics in Chinese children (6-11 years old) with different refractive status using swept-source optical coherence tomography.

BACKGROUND: The anatomic structure of the anterior chamber (AC) helps to explain differences in refractive status in school-aged children and is closely associated with primary angle closure (PAC). The aim of this study was to quantify and analyze the anterior chamber and angle (ACA) characteristics in Chinese children with different refractive status by swept-source optical coherence tomography (SS-OCT). METHODS: In a cross-sectional observational study, 383 children from two primary schools in Shandong Province, China, underwent a complete ophthalmic examination. First, the anterior chamber depth (ACD), anterior chamber width (ACW), angle-opening distance (AOD), and trabecular-iris space area (TISA) were evaluated automatically using a CASIA2 imaging device. AOD and TISA were measured at 500, 750 µm nasal (N1 and N2, respectively), and temporal (T1 and T2, respectively) to the scleral spur (SS). Cycloplegic refraction and axial length (AL) were then measured. According to spherical equivalent refraction (SER), the children were assigned to hyperopic (SER > 0.50D), emmetropic (-0.50D < SER ≤ 0.50D), and myopic groups (SER ≤ -0.50D). RESULTS: Out of the 383 children, 349 healthy children (160 girls) with a mean age of 8.23 ± 1.06 years (range: 6-11 years) were included. The mean SER and AL were - 0.10 ± 1.57D and 23.44 ± 0.95 mm, respectively. The mean ACD and ACW were 3.17 ± 0.24 mm and 11.69 ± 0.43 mm. The mean AOD were 0.72 ± 0.25, 0.63 ± 0.22 mm at N1, T1, and 0.98 ± 0.30, 0.84 ± 0.27 mm at N2, T2. The mean TISA were 0.24 ± 0.09, 0.22 ± 0.09mm2 at N1, T1, and 0.46 ± 0.16, 0.40 ± 0.14mm2 at N2, T2. The myopic group had the deepest AC and the widest angle. Compared with boys, girls had shorter AL, shallower ACD, narrower ACW, and ACA (all p < 0.05). By Pearson's correlation analysis, SER was negatively associated with ACD, AOD, and TISA. AL was positively associated with ACD, ACW, AOD, and TISA. In the multiple regression analysis, AOD and TISA were associated with deeper ACD, narrower ACW, and longer AL. CONCLUSION: In primary school students, the myopic eyes have deeper AC and wider angle. ACD, ACW, AOD, and TISA all increase with axial elongation. ACA is highly correlated with deeper ACD.

Nanomaterial Delivery Vehicles for the Development of Neoantigen Tumor Vaccines for Personalized Treatment.

Tumor vaccines have been considered a promising therapeutic approach for treating cancer in recent years. With the development of sequencing technologies, tumor vaccines based on neoantigens or genomes specifically expressed in tumor cells, mainly in the form of peptides, nucleic acids, and dendritic cells, are beginning to receive widespread attention. Therefore, in this review, we have introduced different forms of neoantigen vaccines and discussed the development of these vaccines in treating cancer. Furthermore, neoantigen vaccines are influenced by factors such as antigen stability, weak immunogenicity, and biosafety in addition to sequencing technology. Hence, the biological nanomaterials, polymeric nanomaterials, inorganic nanomaterials, etc., used as vaccine carriers are principally summarized here, which may contribute to the design of neoantigen vaccines for improved stability and better efficacy.

Simultaneous Detection of Two Extracellular Vesicle Subpopulations in Saliva Assisting Tumor T Staging of Oral Squamous Cell Carcinoma.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Three-Dimensional Magnetic Chip with Extracorporeal Circulation for Circulating Tumor Cell In Vivo Detection and Tumor Growth Inhibition.

Liquid biopsy technology involves taking samples from body fluids in a minimally invasive way and analyzing tumor markers to achieve early diagnosis and efficacy evaluation of tumors. The development of real-time cancer diagnosis and treatment strategies based on liquid biopsy technology is of great significance to cancer management. This paper described an extracorporeal circulation based on a three-dimensional (3D) magnetic chip (3DMC-system) for in vivo detection and real-time monitoring of circulating tumor cells (CTCs). Utilizing biofunctionalized magnetic nanospheres (MNs) with CTC recognition function, this 3DMC-system could effectively achieve the real-time monitoring of CTCs in vivo with good stability and strong anti-interference. Compared with in vitro CTC detection, in vivo detection could not only detect more CTCs but also detect the presence of CTCs in the blood at an early stage of the tumor, when tumor metastasis is not observed in imaging. In addition, due to the flexibility of the chip design, the system can easily add a treatment module to integrate cancer diagnosis and treatment together. With good biocompatibility and high stability, this 3DMC-system is expected to provide a new personalized medical program for cancer patients.

Climatic seasonality challenges the stability of microbial-driven deep soil carbon accumulation across China.

Microbial residues contribute to the long-term stabilization of carbon in the entire soil profile, helping to regulate the climate of the planet; however, how sensitive these residues are to climatic seasonality remains virtually unknown, especially for deep soils across environmental gradients. Here, we investigated the changes of microbial residues along soil profiles (0-100 cm) from 44 typical ecosystems with a wide range of climates (~3100 km transects across China). Our results showed that microbial residues account for a larger portion of soil carbon in deeper (60-100 cm) vs. shallower (0-30 and 30-60 cm) soils. Moreover, we find that climate especially challenges the accumulation of microbial residues in deep soils, while soil properties and climate share their roles in controlling the residue accumulation in surface soils. Climatic seasonality, including positive correlations with summer precipitation and maximum monthly precipitation, as well as negative correlations with temperature annual range, are important factors explaining microbial residue accumulation in deep soils across China. In particular, summer precipitation is the key regulator of microbial-driven carbon stability in deep soils, which has 37.2% of relative independent effects on deep-soil microbial residue accumulation. Our work provides novel insights into the importance of climatic seasonality in driving the stabilization of microbial residues in deep soils, challenging the idea that deep soils as long-term carbon reservoirs can buffer climate change.

Microbial communities in terrestrial surface soils are not widely limited by carbon.

Microbial communities in soils are generally considered to be limited by carbon (C), which could be a crucial control for basic soil functions and responses of microbial heterotrophic metabolism to climate change. However, global soil microbial C limitation (MCL) has rarely been estimated and is poorly understood. Here, we predicted MCL, defined as limited availability of substrate C relative to nitrogen and/or phosphorus to meet microbial metabolic requirements, based on the thresholds of extracellular enzyme activity across 847 sites (2476 observations) representing global natural ecosystems. Results showed that only about 22% of global sites in terrestrial surface soils show relative C limitation in microbial community. This finding challenges the conventional hypothesis of ubiquitous C limitation for soil microbial metabolism. The limited geographic extent of C limitation in our study was mainly attributed to plant litter, rather than soil organic matter that has been processed by microbes, serving as the dominant C source for microbial acquisition. We also identified a significant latitudinal pattern of predicted MCL with larger C limitation at mid- to high latitudes, whereas this limitation was generally absent in the tropics. Moreover, MCL significantly constrained the rates of soil heterotrophic respiration, suggesting a potentially larger relative increase in respiration at mid- to high latitudes than low latitudes, if climate change increases primary productivity that alleviates MCL at higher latitudes. Our study provides the first global estimates of MCL, advancing our understanding of terrestrial C cycling and microbial metabolic feedback under global climate change.

Synthesis and Spectroscopic Properties of Selenophene[3, 2-b]-Fused BODIPYs.

Fusion selenophene endows the chromophore with more intrinsic and special functions. Herein, nonsymmetric selenophene-fused BODIPYs were designed and synthesized starting from the selenophene unit. The fused ring of selenophene not only maintains the rigid structure of BODIPY but also further modulates its spectral properties. The newly prepared dyes possessed many promising properties including large molar extinction coefficients, low fluorescence quantum yields, and moderate singlet oxygen generation. Quantum calculations affirmed that the smaller singlet-triplet energy gap and larger spin-orbit coupling cause efficient intersystem crossing, thus enhancing the singlet oxygen generation yield. Furthermore, selenophene-fused BODIPY exhibited significant phototoxicity with negligible dark cytotoxicity, based on the fluorescence imaging of the reactive oxygen species detection experiment.

Association between Environmental Exposure to Multiclass Organic Pollutants and Sex Steroid Hormone Levels in Women of Reproductive Age.

Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to persistent organic pollutants, with few hormones being investigated. Moreover, measurements from a single blood or urine sample may not be able to reflect long-term status. Using hair analysis, here, we evaluated the relationship between multiclass organic pollutants and sex steroid hormones in 196 healthy Chinese women aged 25-45 years. Associations with nine sex steroid hormones, including progesterone, androstenedione (AD), testosterone (T), estrone (E1), and 17ß-estradiol (E2), and eight related hormone ratios were explored on 54 pollutants from polychlorinated biphenyl (PCB), pesticide, and bisphenol families using stability-based Lasso regression analysis. Our results showed that each hormone was associated with a mixture of at least 10 examined pollutants. In particular, hair E2 concentration was associated with 19 pollutants, including γ-hexachlorocyclohexane, propoxur, permethrin, fipronil, mecoprop, prochloraz, and carbendazim. There were also associations between pollutants and hormone ratios, with pentachlorophenol, dimethylthiophosphate, 3-phenoxybenzoic acid, and flusilazole being related to both E1/AD and E2/T ratios. Our results suggest that exposure to background levels of pesticides PCB180 and bisphenol S may affect sex steroid hormone homeostasis among women of reproductive age.

Eco-Friendly One-Pot Supramolecular-Assembly of P-N Flame Retardant for Fire-Safe Epoxy Resin.

Flame retardant treatment of epoxy resins (EP) to reduce their flammability for extending their range of applications attracts considerable attention. However, the synthesis process of conventional flame retardants is complicated and involves organic hazardous solvents. Meanwhile, how to ensure both the flame-retardant and mechanical properties is a long-standing and actual difficult problem. In this work, a supramolecular flame retardant (named ATPFR) is facilely created by one-pot reaction, using cheap and accessible raw materials in an ecologically benign aqueous solvent. ATPFR is applied to improve the fire safety of EP. With only 5 wt% ATPFR addition, EP can reach the limiting oxygen index of 28.5% and the UL-94 V-0 rating with a significant "blow-out effect." The cone calorimetry test reveals that the EP thermoset with 5 wt% ATPFR has a 75.8% reduction in the peak heat release rate (p-HRR) and a 67.3% reduction in the peak smoke production rate (p-SPR), respectively, compared with the pure EP. Additionally, EP composites with the small amount of ATPFR exhibit a slight decrease and maintain good mechanical properties. Therefore, the facile synthesis and application of this supramolecular flame retardant provide a reliable way for the construction of polymer materials with environment-friendly and effective flame-retardant system.

Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.

OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.

Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents.

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.

Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis, treatment, and the development of drug resistance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. DATA SOURCES: We carried out a systematic review on lncRNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lncRNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in PubMed with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lncRNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. RESULTS: LncRNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting miRNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. CONCLUSIONS: The functional lncRNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

Pan-Plastome of Greater Yam (Dioscorea alata) in China: Intraspecific Genetic Variation, Comparative Genomics, and Phylogenetic Analyses.

Dioscorea alata L. (Dioscoreaceae), commonly known as greater yam, water yam, or winged yam, is a popular tuber vegetable/food crop worldwide, with nutritional, health, and economical importance. China is an important domestication center of D. alata, and hundreds of cultivars (accessions) have been established. However, genetic variations among Chinese accessions remain ambiguous, and genomic resources currently available for the molecular breeding of this species in China are very scarce. In this study, we generated the first pan-plastome of D. alata, based on 44 Chinese accessions and 8 African accessions, and investigated the genetic variations, plastome evolution, and phylogenetic relationships within D. alata and among members of the section Enantiophyllum. The D. alata pan-plastome encoded 113 unique genes and ranged in size from 153,114 to 153,161 bp. A total of four whole-plastome haplotypes (Haps I-IV) were identified in the Chinese accessions, showing no geographical differentiation, while all eight African accessions shared the same whole-plastome haplotype (Hap I). Comparative genomic analyses revealed that all four whole plastome haplotypes harbored identical GC content, gene content, gene order, and IR/SC boundary structures, which were also highly congruent with other species of Enantiophyllum. In addition, four highly divergent regions, i.e., trnC-petN, trnL-rpl32, ndhD-ccsA, and exon 3 of clpP, were identified as potential DNA barcodes. Phylogenetic analyses clearly separated all the D. alata accessions into four distinct clades corresponding to the four haplotypes, and strongly supported that D. alata was more closely related to D. brevipetiolata and D. glabra than D. cirrhosa, D. japonica, and D. polystachya. Overall, these results not only revealed the genetic variations among Chinese D. alata accessions, but also provided the necessary groundwork for molecular-assisted breeding and industrial utilization of this species.

Synthesis and Applications of Supramolecular Flame Retardants: A Review.

The development of different efficient flame retardants (FRs) to improve the fire safety of polymers has been a hot research topic. As the concept of green sustainability has gradually been raised to the attention of the whole world, it has even dominated the research direction of all walks of life. Therefore, there is an urgent calling to explore the green and simple preparation methods of FRs. The development of supramolecular chemistry in the field of flame retardancy is expanding gradually. It is worth noting that the synthesis of supramolecular flame retardants (SFRs) based on non-covalent bonds is in line with the current concepts of environmental protection and multi-functionality. This paper introduces the types of SFRs with different dimensions. SFRs were applied to typical polymers to improve their flame retardancy. The influence on mechanical properties and other material properties under the premise of flame retardancy was also summarized.