Synthesis of ZnO and PEG-ZnO nanoparticles (NPs) with controlled size for biological evaluation.

The objective of this research was to produce the smallest possible ZnO nanoparticles through an adapted wet chemical process and subsequently, to fabricate a core-shell structure utilizing polyethylene glycol (PEG) as the shell component. The synthesis, size, and shape of the NPs were confirmed using advanced techniques. The resulting clustered NPs were round and had a size of 9.8 nm. Both plain and core-shell NPs were tested for their antibacterial properties against multi-drug resistant bacteria strains (E. cloacae, E. amnigenus, S. flexneri, S. odorifacae, Citrobacter, and E. coli), with concentrations of 500, 1000, and 1500 µg ml-1 used for testing. Both types of NPs demonstrated antibacterial activity against the tested pathogens, with the core-shell NPs being more effective. The synthesized NPs were biocompatible with human red blood cells, with a low level of hemolysis observed. The biocompatibility of the core-shell NPs was significantly enhanced by the presence of the PEG added as the shell. In addition, their effectiveness as photosensitizers for cancer treatment via photodynamic therapy (PDT) was evaluated. MTT assay was used to evaluate the cytotoxicity of ZnO and PEG-ZnO, and the results showed that these NPs were able to generate ROS inside tumor cells upon irradiation, leading to apoptosis and cell death, making them a promising candidate for PDT.

Light-Colored Maillard Peptides: Formation from Reduced Fluorescent Precursors of Browning and Enhancement of Saltiness Perception.

The browning formation and taste enhancement of peptides derived from soybean, peanut, and corn were studied in the light-colored Maillard reaction compared with the deep-colored reaction. The fluorescent compounds, as the browning precursors, were accumulated during the early Maillard reaction of peptides and subsequently degraded into dark substances, which resulted in a higher browning degree of deep-colored Maillard peptides (MPs), especially for the MPs derived from corn peptide. However, the addition of l-cysteine in light-colored Maillard reaction reduced the formation of deoxyosones and short-chain reactive α-dicarbonyls, thereby weakening the generation of fluorescent compounds and inhibited the browning of MPs. Synchronously, the peptides were thermally degraded into small peptides and amino acids, which were consumed less during light-colored thermal reaction due to its shorter reaction time at high temperature compared with deep-colored ones, thus contributing to a stronger saltiness perception of light-colored MPs than deep-colored MPs. Besides, the Maillard reaction products derived from soybean and peanut peptides possessed an obvious "kokumi" taste, making them suitable for enhancing the soup flavors.

Efficient Formation of N-(1-Deoxy-d-ribulos-1-yl)-Glutathione via Limited Oxidation and Degradation of Glutathione during the Atmospheric-Vacuum Thermal Reaction.

The efficient preparation of the ribose-glutathione (Rib-GSH) Amadori rearrangement product (RG-ARP) as a potent precursor of meaty flavor was studied through the atmospheric-vacuum thermal reaction. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed that the oxidation and degradation of GSH occurred during the preparation of RG-ARP via the atmospheric thermal reaction, especially at a low molar ratio of Rib to GSH and high reaction temperature. The RG-ARP and the ARPs derived from the products of GSH oxidation and degradation with the participation of Rib were identified by MS/MS as N-(1-deoxy-d-ribulos-1-yl)-glutathione, N-(1-deoxy-d-ribulos-1-yl)-cysteinylglycine, and N-(1-deoxy-d-ribulos-1-yl)-glutathione disulfide. The selective formation of RG-ARP was disrupted due to the multiple consumption pathways of GSH and Rib. The removal of water and the reduction of oxygen content during vacuum dehydration exhibited an obvious inhibitory effect on the oxidation of cysteinyl and the cleavage of glutamyl, limiting the oxidation and degradation of GSH. Meanwhile, the rapid evaporation of water promoted the molecular collision between the reactants, which allowed the glycation reaction of GSH to be advanced and fragmentation of RG-ARP to be inhibited at a mild dehydration temperature. Accordingly, the atmospheric-vacuum thermal reaction was proposed to limit the generation of secondary byproducts and enhance the yield of RG-ARP, enabling the RG-ARP yield to reach 49.23% at 80 °C and a molar ratio of 2:1 (Rib/GSH) for 20 min.

Intrinsic Molecular Mechanisms of Transformation between Isomeric Intermediates Formed at Different Stages of Cysteine-Xylose Maillard Reaction Model through Dehydration.

2-Threityl-thiazolidine-4-carboxylic acid (TTCA) and Amadori rearrangement product (ARP), the isomeric intermediates derived from the cysteine-xylose (Cys-Xyl) Maillard reaction model, possessed the ability to produce similar flavor profile during the thermal process, but the flavor formation or browning rate of heated TTCA was significantly lower than that of ARP. Macroscopically, the yield of TTCA reached the maximum when the moisture content of the reaction system just dropped to nearly 0% during the thermal reaction-vacuum dehydration process. During the subsequent dynamic intramolecular dehydration process, the reaction remained at an early stage of the Maillard reaction, and TTCA was the main intermediate. Thereinto, the water activity of the samples decreased with the increased dehydration time. From a molecular perspective, the dissipation of free water promoted the conversion of combined water to immobilized water and free water, increasing the intramolecular dehydration. Instantaneous high-temperature dehydration during the spray drying process revealed a higher efficiency than the thermal reaction-vacuum dehydration process, which facilitated the specific conversion of substrates to intermediates (TTCA, ARP). The loss of free water and immobilized water was a key driving force for the direct formation of TTCA/ARP, regulating the formation stages of MRIs. The increase of the inlet air temperature could alter the ratio of TTCA and ARP at the equilibrium state.

Promotion or Inhibition Effects of Exogenous Glutathione-Degraded Amino Acids on the Formation of 2,3-Butanedione and Pyrazines via Varied Pathways of Interaction with α-Dicarbonyl Compounds Derived from N-(1-Deoxy-d-xylulos-1-yl)-alanine.

The contribution of glutathione (GSH) and free amino acids degraded from GSH to the generation of pyrazines and 2,3-butanedione was illustrated during their interaction in the thermal treatment of the Amadori compound of alanine and xylose (ARP). GSH-degraded amino acids, glutamic acid (Glu), cysteine (Cys), and glycine (Gly), but not pyroglutamic acid (pGlu), could effectively capture α-dicarbonyls to facilitate the formation of pyrazines when ARP was heated with GSH. Deoxypentosones, the precursors of 2,3-butanedione, were largely consumed in the ARP-GSH model by the interaction with GSH and its degradative Cys compared with the ARP model. The addition of GSH and deoxypentosones inhibited the further degradation of deoxypentosones, resulting in less formation of 2,3-butanedione and other α-dicarbonyl compounds. Meanwhile, the reaction between GSH-degraded Cys and deoxypentosones to form sulfur-containing compounds such as thiols accelerated the consumption of deoxypentosones; thereby, the formation of 2,3-butanedione was severely interfered. However, this inhibition was compensated for by the GSH-degraded Gly through the addition between Gly and MGO and the subsequent deamination. The involvement of exogenous GSH could simultaneously boost the yields of 2,3-butanedione and pyrazines compared with those of ARP heated alone. As the degree of GSH degradation strengthened in the ARP-thermal-degraded GSH models, the yields of both pyrazines and 2,3-butanedione steadily increased.

Regulated Formation of Inhibited Color and Enhanced Flavor Derived from Heated 2-Threityl-Thiazolidine-4-Carboxylic Acid with Additional Cysteine Targeting at Different Degradation Stages.

This study explored the addition of cysteine (Cys) affecting the color formation of heated 2-threityl-thiazolidine-4-carboxylic acid (TTCA) models under different reaction conditions and pointed out that temperature was considered to be the key parameter influencing the color inhibition behavior of Cys on TTCA reaction models. Results revealed that additional Cys not only controlled the reaction progress and blocked the formation pathway of browning but also changed the formation rate, intensity, and profile of the flavor generated from the TTCA reaction model. Meanwhile, the mechanism of Cys simultaneously regulating the formation of color and flavor was revealed through monitoring of the characteristic downstream products during TTCA degradation and model reaction systems. At the initial stage, the additional Cys acted as a color inhibitor before the deoxyxylosone degradation, preventing the formation of downstream browning precursors. With the continuous depletion of Cys as well as the generation of furans or α-dicarbonyl compounds, Cys became a flavor enhancer to act on the browning precursors and to provide more sulfur/nitrogen elements for the TTCA thermal reaction system. Therefore, Cys had the potential to act as both color inhibitor and flavor fortifier to match with TTCA for the preparation of a light-colored flavoring base with a desired flavor during thermal processing.

Formation of Fluorescent Maillard Reaction Intermediates of Peptide and Glucose during Thermal Reaction and Its Mechanism.

The dynamic changes in fluorescence intensity of the Maillard reactions of l-alanyl-l-glutamine (Ala-Gln)/Diglycine (Gly-Gly)/glycyl-l-glutamine (Gly-Gln) and glucose were investigated. It was found that the fluorescence intensity would increase with the reaction time; however, it would decrease after longer heating at higher temperatures, which was accompanied by rapid browning. The strongest intensity occurred at 45, 35, and 35 min at 130 °C for Ala-Gln, Gly-Gly, and Gly-Gln systems, respectively. The simple model reactions of Ala-Gln/Gly-Gly and dicarbonyl compounds were selected to reveal the formation and mechanism of fluorescent Maillard compounds. It was confirmed that both GO and MGO could react with peptides to form fluorescent compounds, especially GO, and this reaction was sensitive to temperature. The mechanism was also verified in the complex Maillard reaction of pea protein enzymatic hydrolysates.

Preparation of Saltiness-Enhancing Enzymatic Hydrolyzed Pea Protein and Identification of the Functional Small Peptides of Salt Reduction.

According to the correlation of saltiness determined by electronic tongue and perceived NaCl concentration, favorable enzymatic hydrolysis parameters were achieved to prepare the saltiness enhancing mixture peptides from pea protein. Six peptide fractions (F1, F2, F3, F4, F5, and F6) were isolated using Sephadex G-10 gel filtration. Among them, fraction F4 (0.1%) exhibited the highest saltiness (5.90 ± 0.03). The amino acid sequences of five main peptides identified by time-of-flight mass spectrometry were Tyr-Trp (367.40 Da), Gly-Glu-His-Glu (470.43 Da), Glu-Arg-Phe-Gly-Pro (604.65 Da), Gly-Ala-Gly-Lys (331.37 Da), and Pro-Gly-Ala-Gly-Asn (414.41 Da). Tyr-Trp (0.01%) in 0.4% NaCl solution had a 20% saltiness-enhancement compared with 0.4% NaCl solution. More salivary aldosterone was secreted after tasting hydrolysate or Tyr-Trp solutions via enzyme-linked immunosorbent assay, reflecting the improvement of human sensitivity to saltiness. Thereby, the saltiness-enhancing effect was confirmed for the small peptides from hydrolyzed pea protein and the main contributor was further identified.

Gastric lymphoepithelial-like carcinoma presenting as a sub-mucosal mass: a case report and literature review.

BACKGROUND: Lymphoepithelioma-like carcinoma of the stomach (LELC), also known as carcinoma with lymphoid stroma of the stomach, is a rare type of gastric cancer, accounting for approximately 1-4% of all gastric cancers. It is mainly associated with Epstein-Barr virus (EBV) infection. Here, we report a case of gastric lymphoepithelial-like carcinoma presenting as a submucosal mass that tested negative for EBV. CASE DESCRIPTION: a 70-year-old patient was diagnosed with a gastric mass through routine endoscopy. There was no abdominal pain, fever, hematemesis, chills, or other discomfort, and the patient had a history of hypertension. The complete blood count, blood chemistry, and tumor indices were normal, and the results for EBV infection were also negative. According to EUS, it was diagnosed as a gastric stromal tumor. The patient underwent endoscopic submucosal dissection (ESD). Pathological exams suggested that it was a low-differentiated carcinoma, and surgical dissection was performed. CONCLUSION: Cases of gastric LELC are rare, and clinicians need to improve their understanding of the disease to avoid misdiagnosis. The etiology and pathogenesis of this disease need further investigation.

Application of ZnO-NRs@Ni-foam substrate for electrochemical fingerprint of arsenic detection in water.

Arsenic (As3+) is the most carcinogenic and abundantly available heavy metal present in the environment. Vertically aligned ZnO nanorod (ZnO-NR) growth was achieved on metallic nickel foam substrate via a wet chemical route and it was used as an electrochemical sensor towards As(iii) detection in polluted water. Crystal structure confirmation, surface morphology observation and elemental analysis of ZnO-NRs were conducted using X-ray diffraction, field-emission scanning electron microscopy and energy-dispersive X-ray spectroscopy, respectively. Electrochemical sensing performance of ZnO-NRs@Ni-foam electrode/substrate was investigated via linear sweep voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy in a carbonate buffer solution of pH = 9 and at different As(iii) molar concentrations in solution. Under optimum conditions, the anodic peak current was found proportional to the arsenite concentration from 0.1 µM to 1.0 µM. The achieved values for limit of detection and limit of quantification were 0.046 ppm and 0.14 ppm, respectively, which are far lower than the recommended limits for As(iii) detection in drinking water as suggested by the World Health Organization. This suggests that ZnO-NRs@Ni-foam electrode/substrate can be effectively utilized in terms of its electrocatalytic activity towards As3+ detection in drinking water.

Cysteine-Induced pH-Dependent Formation of Thiols and Sulfides or 2-Acetylthiazole and Pyrazines during Thermal Treatment of N-(1-Deoxy-d-xylulos-1-yl)-alanine.

The influence of pH was studied on volatile flavor formation during thermal treatment of an Amadori rearrangement product (ARP) with or without the addition of cysteine (Cys). The formation of thiols and sulfides or 2-acetylthiazole and pyrazines induced by Cys during thermal degradation of ARP was pH-dependent. At low pH levels, the hydrolysis of Cys to hydrogen sulfide (H2S) was promoted, giving rise to the increase of thiols and sulfides with an obvious meaty aroma. However, alkaline conditions were beneficial for enhancing the cyclization or transformation of imine to the enol structure, which strengthened the formation of 2-acetylthiazole and pyrazines with a roasted and nutty aroma. The imine was derived from the nucleophilic addition of Cys and methylglyoxal (MGO) and subsequent decarboxylation. At pH 8, Cys-induced variation of the flavor profile was weakened during thermal degradation of ARP. Accordingly, the combinational effect of pH and added Cys could be beneficial for achieving the desirable flavors during thermal processing of ARP.

Reduced asynchronism between regenerative cysteine and fragments of deoxyosones promoting formation of sulfur-containing compounds through extra-added xylose and elevated temperature during thermal processing of 2­threityl-thiazolidine-4-carboxylic acid.

The flavor intensity of thermally processed 2­threityl-thiazolidine-4-carboxylic acid (TTCA) was significantly improved to 1.56 times of that generated from MRPs, but its flavor profile was not as desirable as that of fresh MRPs. The synergistic effect between the additional xylose (Xyl) and elevated temperature was proposed and confirmed via the quantitative analyses of regenerative cysteine (Cys) and fragments of deoxyosones (MGO/GO), which reduced the asynchronism between the formation of released Cys from degraded TTCA and retro-aldolisation products of the intermediate deoxyosones. This synergistic effect further enhanced the Strecker degradation of Cys as well as its thermal degradation and thereby promoted the formation of characteristic flavor substances including sulfur-containing compounds and pyrazines, and the total concentrations of TTCA reaction model reached 205.954 µg/L with additional Xyl at 140 °C. Model reaction systems were employed to verify this hypothesis and the proposed mechanism was further elucidated through isotope labeling technique.

Stone clearance and complication rate of micro percutaneous nephrolithotomy and retrograde intrarenal surgery for lower pole renal stone: A randomized trial.

Background: The use of unhealthy food and a sedentary lifestyle increases daily health problems. Renal stones are one among others. Endourology promises the minimum complications and the highest stone clearance rate. Indications of the two procedures overlap micro-PCNL and RIRS. The objective was to evaluate stone clearance and complication rate of micro-PCNL and RIRS for lower pole renal stones. Methods: The research design of this study was a randomized trial and was done after approval of the ethical review committee. The sampling technique was consecutive sampling at the Urology department. Patients included in the study according to inclusion criteria were 96 in number. Randomization into two groups (RIRS vs micro-PCNL) was done by even odd method. All the procedure was done by a single senior urologist. Results: Their ratio among males and females was 2:1. Mean LOS in the RIRS group was 2.89±0.86 days and in the micro-PCNL group 2.58±0.65 days (p=0.047). The complication rate in the RIRS group was 6.2% and 8.3% in micro-PCNL (p=0.695). Mean post-operative haemoglobin was 12.30±1.07 g/dL among the RIRS group and among the micro-PCNL group it was 11.21±1.08 g/dL (p<0.001). There was an average haemoglobin drop in the micro-PCNL group of 1.09±0.01 g/dL. 75% clearance of stone after one session was achieved in the RIRS group while 79.2% was achieved in the micro-PCNL group (p=0.627). Conclusion: Length of hospital stay (LOS) and stone clearance rate (SFR) were similar in both groups with insignificant statistical differences. There is a need to conduct more studies with a large number of study participants and involving multi-centers.

Corrigendum: Long non-coding RNAs as molecular biomarkers in cholangiocarcinoma.

[This corrects the article DOI: 10.3389/fcell.2022.890605.].

Glycine, Diglycine, and Triglycine Exhibit Different Reactivities in the Formation and Degradation of Amadori Compounds.

A series of Amadori compounds of glucose were prepared from glycine (G-ARP), diglycine (DiG-ARP), and triglycine (TriG-ARP), and identified by UPLC-MS/MS and NMR. The formation rate of ARPs was TriG-ARP > DiG-ARP > G-ARP, and their activation energies were 63.48 kJ/mol (TriG-ARP), 72.84 kJ/mol (DiG-ARP), and 84.76 kJ/mol (G-ARP), respectively, suggesting that ARP was formed more easily from small peptides than from amino acid. Although 1-DG was formed much more difficultly than 3-DG, the same order of the formation of 1-DG, 3-DG, and browning was DiGly > TriGly > Gly. It was also confirmed that more methylglyoxal and glyoxal would be formed from small peptides than equimolar amino acids. Compared with free amino acid, ARP, deoxyglycosones, and their secondary degradation products were more easily formed from dipeptide and tripeptide, thereby stronger browning occurred and higher reactivity was exhibited in Maillard reaction of di- or tripeptide.

Competitive Formation of 2,3-Butanedione and Pyrazines through Intervention of Added Cysteine during Thermal Processing of Alanine-Xylose Amadori Compounds.

The intervention of cysteine (Cys) on the formation of 2,3-butanedione and pyrazines was evaluated during the thermal processing of the alanine-xylose Amadori compound (AX-ARP). With the involvement of Cys, the competitive formation of 2,3-butanedione and pyrazines was induced. The formation of 2,3-butanedione in the AX-ARP/Cys model was suppressed due to the inhibitory effect of the precursors of 2,3-butanedione like deoxypentosones, while the added Cys in the AX-ARP/Cys model competed with the recovered alanine (Ala) to capture glyoxal and methylglyoxal to make up for the absence of pyrazines in the AX-ARP model at an initial pH value of 7. The content of pyrazines increased from 0 up to 16.48 µg/L (120 °C, 120 min). Exogenous Cys itself showed lower reactivity with 2,3-butanedione through the Strecker degradation reaction; while the pH was increased to 8, the degradative products of Cys were facilitated to consume the residual 2,3-butanedione giving rise to the formation of 2,4,5-trimethylthiazole at 120 °C. It was the degradative products of Cys that accelerated the reaction for consumption of 2,3-butanedione rather than Cys itself. Additionally, the inhibitory effect of Cys on 2,3-butanedione formation was weakened under a basic condition, while the promotional effect on the formation of pyrazines was further boosted. With more Cys participating in the process of AX-ARP thermal degradation, the formation of 2,3-butanedione was further inhibited, while the yields of pyrazines were increased.

Formation Priority of Pyrazines and 2-Acetylthiazole Dependent on the Added Cysteine and Fragments of Deoxyosones during the Thermal Process of the Glycine-Ribose Amadori Compound.

In this study, it was found that extra-added cysteine (Cys) became involved in volatile compound formation during the Maillard reaction of the glycine-ribose Amadori rearrangement product (GR-ARP). The priority of the Cys reaction with different α-dicarbonyls and its dependence on the Cys dosage were investigated. At the same concentrations of methylglyoxal (MGO) and glyoxal (GO), it was found that 2-acetylthiazole was the dominant product when the molar ratio of Cys to MGO was 1:1, while formation of pyrazines was improved when the Cys percentage increased. Cys preferentially reacted with MGO first rather than GO to exclusively generate 2-acetylthiazole at a high yield. The concentration of 2-acetylthiazole quickly increased up to a plateau and remained stable during further heat treatment. When MGO was totally consumed, remaining Cys began to react with GO through the predominant pathway where the keto form of carbonylcysteimine derived from Cys and GO was hydrolyzed to recover GO with cysteamine formation, whereas the hydrolysis reactivity of enolized carbonylcysteimine as the Strecker pathway for generation of pyrazines was relatively low. During the heat treatment of GR-ARP, the constantly lower ratios of α-dicarbonyls to Cys led to inhibited formation of 2-aminopropanal, which accounted for the decreased methylpyrazine yields.

Glycine-Xylose Amadori Compound Formation Tracing through Maillard Browning Inhibition by 2-Threityl-thiazolidine-4-carboxylic Acid Formation from Deoxyosone and Exogenous Cysteine.

The browning inhibition of cysteine on the Maillard reaction of glycine-xylose performed under stepwise increased temperature was investigated. The browning degrees of the final products prepared with cysteine addition at different time points were found dissimilar, and the addition time point of cysteine yielding the lightest browning products was consistent with the time when the glycine-xylose Amadori rearrangement product (GX-ARP) reached its maximum yield. To clarify the reason for browning inhibition caused by cysteine, the evolution of key browning precursors formed in the GX-ARP model with cysteine involved was investigated by HPLC with a diode array detector. The results on the browning degree of the thermal reaction products of GX-ARP with cysteine addition showed great inhibition of α-dicarbonyl generation, which resulted in a significant increase in the activation energy of GX-ARP conversion to browning formation during heat treatment. Strong evidence suggested that the additional cysteine got involved in GX-ARP degradation and reacted with the deoxyosones derived from GX-ARP to yield cyclic 2-threityl-thiazolidine-4-carboxylic acid (TTCA). TTCA formation shunted the degradation of deoxyosones into short-chain α-dicarbonyls, which were important browning precursors, and consequently inhibited the Maillard browning.

Promoted Formation of Pyrazines and Sulfur-Containing Volatile Compounds through Interaction of Extra-Added Glutathione or Its Constituent Amino Acids and Secondary Products of Thermally Degraded N-(1-Deoxy-d-ribulos-1-yl)-Glutathione.

An Amadori rearrangement product (ARP) derived from ribose (Rib) and glutathione (GSH) was prepared and identified as N-(1-deoxy-d-ribulos-1-yl)-glutathione by ultraperformance liquid chromatography-tandem mass spectrometry and NMR. Thermal treatment of the ARP aqueous solution was conducted, and a relatively high temperature was found to accelerate the degradation of the ARP. The concentration of furans formed at 120 °C was more than 6.39 times that at 100 °C, and especially, the high temperature favored the formation of furfural and 4-hydroxy-5-methyl-3(2H)-furanone through deoxyosone dehydration. The promoting role of extra-added GSH or its constituent amino acids was investigated in the volatile formation during thermal processing of the ARP. Both, the added GSH and its constituent amino acids, could timely capture glyoxal (GO) and methylglyoxal (MGO) to facilitate Strecker degradation, which improved pyrazine formation. Compared with glycine and glutamic acid, cysteine was the most effective extra-added amino acid to react with GO and MGO to produce pyrazine and methylpyrazine. More importantly, the cysteine degraded from extra-added GSH effectively accelerated the generation of sulfur-containing volatile compounds through the reaction of cysteine degradation products with furans and shorter-chain α-dicarbonyl compounds.

Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a biliary system cancer that has the characteristics of strong invasiveness, poor prognosis, and few therapy choices. Furthermore, the absence of precise biomarkers for early identification and prognosis makes it hard to intervene in the early phase of initial diagnosis or recurring cholangiocarcinoma following surgery. Encouragingly, previous studies found that long non-coding RNA (lncRNA), a subgroup of RNA that is more than 200 nucleotides long, can affect cell proliferation, migration, apoptosis, and even drug resistance by altering numerous signaling pathways, thus reaching pro-cancer or anti-cancer outcomes. This review will take a retrospective view of the recent investigations on the work of lncRNAs in cholangiocarcinoma progression and the potential of lncRNAs serving as promising clinical biomarkers and therapeutic targets for CCA.