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Golgi phosphoprotein 3 (GOLPH3) has been reported as an oncogene in various tumors; however, the role and function of GOLPH3 and its relevant molecular mechanism in cholangiocarcinoma (CCA) are unclear. Herein, GOLPH3 expression in CCA tissues was observed to be significantly higher than that in paired adjacent noncancerous tissues. Clinicopathological analysis showed that GOLPH3 expression correlated positively with the tumor-node-metastasis stage. In addition, GOLPH3 expression correlated inversely with the overall survival of patients with CCA. Multivariate analysis showed that GOLPH3 was an independent prognostic factor for patients with CCA. Transcriptome analysis (RNA sequencing) of GOLPH3 knockdown cells showed that the expression levels of nine ferroptosis-related genes were significantly changed, indicating the important biological function of GOLPH3 in ferroptosis in CCA cells. Furthermore, GOLPH3 knockdown could significantly promote Erastin-induced ferroptosis in vitro and suppress tumor growth in vivo. Overexpression of GOLPH3 had the opposite effect on this phenotype. Further studies revealed that GOLPH3 knockdown was significantly associated with a decrease in cysteine content, an accumulation of the lipid peroxidation product malondialdehyde, an increase in reactive oxygen species, and sensitized CCA cells to Erastin-induced ferroptosis. Moreover, changes in GOLPH3 expression were found to be consistent with the expression of light chain subunit solute carrier family 7 member 11 (SLC7A11). Thus, our study suggested that GOLPH3 functions as an oncoprotein in CCA and may suppress ferroptosis by facilitating SLC7A11 expression, suggesting that GOLPH3 could serve as a therapeutic target for CCA treatment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Ferroptose , Proteínas de Membrana , Humanos , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Ferroptose/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Análise MultivariadaRESUMO
An optical frequency domain reflectometry (OFDR) shape sensor was demonstrated based on a femtosecond-laser-inscribed weak fiber Bragg grating (WFBG) array in a multicore fiber (MCF). A WFBG array consisting of 60 identical WFBGs was successfully inscribed in each core along a 60â cm long MCF using the femtosecond-laser point-by-point technology, where the length and space of each WFBG were 2 and 8â mm, respectively. The strain distribution of each core in two-dimensional (2D) and three-dimensional (3D) shape sensing was successfully demodulated using the traditional cross correlation algorithm, attributed to the accurate localization of each WFBG. The minimum reconstruction error per unit length of the 2D and 3D shape sensors has been improved to 1.08% and 1.07%, respectively, using the apparent curvature vector method based on the Bishop frame.
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Neuroinflammation is being increasingly recognized as a vital factor in the development of various neurological and neuropsychiatric diseases. Lipopolysaccharides (LPS), an outer membrane component of gram-negative bacteria, can trigger innate immune responses, resulting in neuroinflammation and subsequent cognitive deficits. The expression of glutamate receptors (GluRs) on glial cells can induce glial activation. Therefore, we hypothesized that repeated LPS exposure can increase GluR levels, promoting microglial activation and ultimately affecting synaptic plasticity and cognitive function. In this study, C57/BL6 mice were repeatedly exposed to LPS to construct a neuroinflammation animal model. The levels of GluRs, inflammatory cytokines, ionized calcium-binding adaptor molecule 1, postsynaptic density protein 95, synaptophysin 38, NMDA receptor 2 A, and NMDA receptor 2B (GluN2B) were measured in the hippocampi. Furthermore, dendritic spine density in the CA1 hippocampal region was determined. Repeated LPS exposure induced cognitive impairments and microglial activation and increased GluR1 and GluR2 levels. This was accompanied by a significant decrease in GluN2B expression and dendritic spine density in the hippocampi. However, CFM-2, an α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, reversed these anomalies. Furthermore, minocycline, a microglial inhibitor, reversed these anomalies and downregulated GluR2 but not GluR1 expression. In summary, we demonstrated that GluR2 plays an essential role in microglia-induced neuroinflammation, resulting in synaptic plasticity and cognitive impairment induced by repeated exposure to LPS.
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Disfunção Cognitiva , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Receptores de AMPA , Animais , Lipopolissacarídeos/toxicidade , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Receptores de AMPA/metabolismo , Masculino , Doenças Neuroinflamatórias/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Camundongos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Microglia/metabolismo , Microglia/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacosRESUMO
Defect engineering plays a pivotal role in regulating electronic structure and facilitating charge transfer, yielding captivating effects on third-order nonlinear optical (NLO) properties. In this work, we utilized a mixed-linker strategy to intentionally disrupt the initial periodic arrangement of UiO-66 and construct defects. Specifically, we incorporated tetrakis(4-carboxyphenyl)porphyrin (TCPP) with an exceptionally electron-rich delocalization system into the framework of UiO-66 using a one-pot solvothermal method, ingeniously occupying the partial distribution sites of the Zr6 clusters. Compared to UiO-66, the NLO absorption and refraction performance of TCPP/UiO-66 were significantly improved. Additionally, due to the presence of nitrogen-rich sites that can accommodate metal ions in the porphyrin ring of TCPP, Co(II), Ni(II), Cu(II), and Zn(II) are introduced into TCPP/UiO-66, extending the d-π conjugation effect to further regulate the defects. The NLO absorption behavior transforms saturation absorption (SA) to reverse saturation absorption (RSA), while the refraction behavior shifts from self-defocusing to self-focusing. This work shows that defects can effectively regulate the electronic structure, while TCPP plays a crucial role in significantly enhancing electron delocalization.
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Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum.
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2-bromoacetamide (BAcAm) is an emerging class of unregulated disinfection by-products (DBPs), with potent cytogenetic and developmental toxicity in animals. However, whether BAcAm exerts toxic effects on mammalian oocyte quality remains to be elucidate. In this research, we investigated the effect of BAcAm on mouse and human oocyte maturation with an in vitro culture system. Our results revealed that BAcAm exposure hindered the extrusion of the first polar body, disrupted the spindle organization and reduced the competence of embryo development after fertilization in the mouse oocytes. Results of single-cell RNA sequencing (scRNA-seq) showed that 605 differentially expressed genes (DEGs) were identified in the BAcAm exposed mouse oocytes, among which 366 were up-regulated and 239 were down-regulated. Gene Ontology (GO) analysis further revealed that DEGs were mainly enriched in mitochondrial functions, oxidative stress, cytoskeleton, endoplasmic reticulum (ER), Golgi and protein synthesis, DNA damage and apoptosis. We then conducted further tests in these aspects and discovered that BAcAm exposure principally perturbed the function of microtubule and actin cytoskeleton. This finding was confirmed in human oocytes. Overall, our data suggest that BAcAm exposure disturbs the cytoskeleton function, thus impairing oocyte maturation. These data, for the first time, provide a comprehensive view for the toxic effects of BAcAm on oocyte maturation.
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Citoesqueleto , Oogênese , Humanos , Animais , Camundongos , Citoesqueleto/metabolismo , Oócitos/metabolismo , Mitocôndrias/metabolismo , Microtúbulos/metabolismo , MamíferosRESUMO
The present study aimed to develop low-sodium curing agents for dry-cured meat products. Four low-sodium formulations (SPMA, SPM, SP, and SM) were used for dry-curing meat. The physicochemical properties and flavor of the dry-cured meat were investigated. The presence of Mg2+ ions hindered the penetration of Na+ into the meat. The weight loss, moisture content, and pH of all low-sodium salt groups were lower than those of S. Mg2+ addition increased the water activity (Aw) of SPMA, SPM, and SM. Dry-curing meat with low-sodium salts promoted the production of volatile flavor compounds, with Mg2+ playing a more prominent role. Furthermore, low-sodium salts also promoted protein degradation and increased the content of free amino acids in dry-cured meat, especially in SM. Principal component analysis (PCA) showed that the low-sodium salts containing Mg2+ were conducive to improving the quality of dry-cured meat products. Therefore, low-sodium salts enriched with Mg2+ become a desirable low-sodium curing agent for achieving salt reduction in dry-cured meat products.
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Magnésio , Produtos da Carne , Produtos da Carne/análise , Magnésio/análise , Magnésio/química , Animais , Sódio/análise , Sódio/química , Sais/química , Paladar , Aromatizantes/análise , Aromatizantes/química , Concentração de Íons de Hidrogênio , Aminoácidos/análise , Aminoácidos/química , Manipulação de Alimentos/métodosRESUMO
AIM: Splenic vessel-preserving spleen-preserving distal pancreatectomy (SVP-SPDP) has a lower risk of splenic infarction than the splenicvessel-sacrificing SPDP, but it is more technically demanding. Learning curve of robotic-assisted SVP-SPDP (RSVP-SPDP) remains unreported. This study sought to analyze the perioperative outcomes and learning curve of RSVP-SPDP by one single surgeon. METHODS: Seventy-four patients who were intended to receive RSVP-SPDP at the First Affiliated Hospital of Sun Yat-sen University between May 2015 and January 2023 were included. The learning curve were retrospectively analyzed by using cumulative sum (CUSUM) analyses. RESULTS: Sixty-two patients underwent RSVP-SPDP (spleen preservation rate: 83.8%). According to CUSUM curve, the operation time (median, 318 vs. 220 min; P < 0.001) and intraoperative blood loss (median, 50 vs. 50 mL; P = 0.012) was improved significantly after 16 cases. Blood transfusion rate (12.5% vs. 3.4%; P = 0.202), postoperative major morbidity rate (6.3% vs. 3.4%; P = 0.524), and postoperative length-of-stay (median, 10 vs. 8 days; P = 0.120) improved after 16 cases but did not reach statistical difference. None of the patients had splenic infarction or abscess postoperatively. CONCLUSION: RSVP-SPDP was a safe and feasible approach for selected patients after learning curve. The improvement of operation time and intraoperative blood loss was achieved after 16 cases.
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Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Infarto do Baço , Cirurgiões , Humanos , Pancreatectomia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Infarto do Baço/etiologia , Infarto do Baço/cirurgia , Curva de Aprendizado , Resultado do Tratamento , Artéria Esplênica/cirurgia , Neoplasias Pancreáticas/cirurgiaRESUMO
This study aimed to investigate the synergistic effects of high-intensity ultrasound (0, 5, 10, 15, and 20 min) in combination with L-lysine (15 mM) on improving the solubility and flavour adsorption capacity of myofibrillar proteins (MPs) in low-ion-strength media. The results revealed that the ultrasound treatment for 20 min or the addition of L-lysine (15 mM) significantly improved protein solubility (p < 0.05), with L-lysine (15 mM) showing a more pronounced effect (p < 0.05). The combination of ultrasound treatment and L-lysine further increased solubility, and the MPs treated with ultrasound at 20 min exhibited the best dispersion stability in water, which corresponded to the lowest turbidity, highest absolute zeta potential value, and thermal stability (p < 0.05). Based on the reactive and total sulfhydryl contents, Fourier transform infrared spectroscopy, and fluorescence spectroscopy analysis, the ultrasound treatment combined with L-lysine (15 mM) promoted the unfolding and depolymerization of MPs, resulting in a larger exposure of SH groups on the surface, aromatic amino acids in a polar environment, and a transition of protein conformation from α-helix to ß-turn. Moreover, the combined treatment also increased the hydrophobic bonding sites, hydrogen-bonding sites, and electrostatic effects, thereby enhancing the adsorption capacity of MPs to bind kenone compounds. The findings from this study provide a theoretical basis for the production and flavour improvement of low-salt MP beverages and the utilisation of meat protein.
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In this study, we have successfully produced a corn starch-based composite film through the casting method, formulated with clove essential oil nanoemulsion (NCEO) and corn starch. The physical and chemical changes of the composite films were investigated at various concentrations (10 %, 20 % and 40 %) of NCEO. Furthermore, the non-contact preservation effects of the composite films on bread during 15-day storage were also examined in this study. As the concentration of NCEO increased, the composite films presented a gradual thinning, roughening, and yellowing in appearance. Following this, the water content, water vapor permeability rate, and elongation at break of the films decreased, while their hydrophobicity, tensile strength, antioxidant and antimicrobial activity increased accordingly. Through FT-IR, X-ray diffraction and thermal gravimetric analysis, it was demonstrated that NCEO has strong compatibility with corn starch. Additionally, the indices' analysis indicated that utilizing the composite film incorporating 40 % NCEO can significantly boost the shelf life and quality of bread. Moreover, it was revealed that application of the non-contact treatment with composite film could potentially contribute certain preservation effects towards bread. In light of these findings, the composite film with non-contact treatment exhibits potential as an effective, safe, and sustainable preservation technique for grain products.
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Óleos Voláteis , Syzygium , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleo de Cravo/farmacologia , Óleo de Cravo/química , Amido/química , Espectroscopia de Infravermelho com Transformada de Fourier , Pão , Permeabilidade , Embalagem de AlimentosRESUMO
To expound on the correlation between the microorganism communities and the formation of off-odour in Xuanwei ham, the microorganism communities and volatile compounds were investigated in the biceps femoris (BF) and semimembranosus (SM) of Xuanwei ham with different quality grades (normal ham and spoiled ham). The single molecule real-time sequencing showed that differential bacteria and fungi were more varied in normal hams than in spoiled hams. Headspace solid-phase microextraction-gas chromatography (HS-SPME-GC-MS) results indicated that aldehydes and alcohols were significantly higher in spoiled hams than those in normal hams (p < 0.05). The off-odour of spoiled hams was dominated by ichthyic, malodourous, sweaty, putrid, sour, and unpleasant odours produced by compounds such as trimethylamine (SM: 13.05 µg/kg), hexanal (BF: 206.46 µg/kg), octanal (BF: 59.52 µg/kg), methanethiol (SM: 12.85 µg/kg), and valeric acid (BF: 15.08 µg/kg), which are positively correlated with Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Pseudomonas sp., Aspergillus ruber, and Moraxella osloensis. Furthermore, the physicochemical property and quality characteristics results showed that high moisture (BF: 56.32 g/100 g), pH (BF: 6.63), thiobarbituric acid reactive substances (TBARS) (SM: 1.98 MDA/kg), and low NaCl content (SM: 6.31%) were also responsible for the spoilage of hams with off-odour. This study provided a deep insight into the off-odour of Xuanwei ham from the perspective of microorganism communities and a theoretical basis for improving the flavour and overall quality of Xuanwei hams.
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Ciprofol is a novel short-acting intravenous anaesthetic developed in China that is mainly metabolized by cytochrome P450 2B6 (CYP2B6) and uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). Currently, insufficient evidence is available to support drugâdrug interactions between ciprofol and CYP2B6 inactivators. Here, we established a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to assess the concentration of ciprofol and investigated the effects of psoralen and clopidogrel on the metabolism of ciprofol in liver microsomes and rats. In rat and human liver microsomes, the median inhibitory concentration (IC50) values of psoralen were 63.31 µmol·L-1 and 34.05 µmol·L-1, respectively, showing mild inhibitory effects on ciprofol metabolism, whereas the IC50 values of clopidogrel were 6.380 µmol·L-1 and 2.565 µmol·L-1, respectively, with moderate inhibitory effects. SD rats were randomly divided into three groups: psoralen (27 mg·kg-1), clopidogrel (7.5 mg·kg-1), and the same volume of 0.5% carboxy methyl cellulose. After 7 days, all rats were injected with 2.4 mg·kg-1 ciprofol. Compared with the control group, the AUC and MRT values of ciprofol in the psoralen and clopidogrel groups were significantly greater, whereas the CL values were significantly lower. In addition, the durations of loss of righting reflex (LORR) in the psoralen and clopidogrel groups were 16.1% and 23.0% longer than that in the control group, respectively. In conclusion, psoralen and clopidogrel inhibit ciprofol metabolism to different degrees and prolong the duration of LORR in rats.
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Clopidogrel , Citocromo P-450 CYP2B6 , Microssomos Hepáticos , Ratos Sprague-Dawley , Animais , Humanos , Clopidogrel/metabolismo , Clopidogrel/farmacologia , Ratos , Microssomos Hepáticos/metabolismo , Masculino , Citocromo P-450 CYP2B6/metabolismo , Inibidores do Citocromo P-450 CYP2B6/metabolismo , Inibidores do Citocromo P-450 CYP2B6/farmacologia , Ticlopidina/metabolismo , Ticlopidina/farmacologia , Ticlopidina/análogos & derivados , Ficusina/farmacologia , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Fenilacetatos , TiofenosRESUMO
Long-term excessive intake of sodium negatively impacts human health. Effective strategies to reduce sodium content in foods include the use of salty and salt taste-enhancing peptides, which can reduce sodium intake without compromising the flavor or salt taste. Salty and salt taste-enhancing peptides naturally exist in various foods and predominantly manifest as short-chain peptides consisting of < 10 amino acids. These peptides are primarily produced through chemical or enzymatic hydrolysis methods, purified, and identified using ultrafiltration + gel filtration chromatography + liquid chromatography-tandem mass spectrometry. This study reviews the latest developments in these purification and identification technologies, and discusses methods to evaluate their effectiveness in saltiness perception. Additionally, the study explores four biological channels potentially involved in saltiness perception (epithelial sodium channel, transient receptor potential vanilloid 1, calcium-sensing receptor (CaSR), and transmembrane channel-like 4 (TMC4)), with the latter three primarily functioning under high sodium levels. Among the channels, salty taste-enhancing peptides, such as γ-glutamyl peptides, may co-activate the CaSR channel with calcium ions to participate in saltiness perception. Salty taste-enhancing peptides with negatively charged amino acid side chains or terminal groups may replace chloride ions and activate the TMC4 channel, contributing to saltiness perception. Finally, the study discusses the feasibility of using these peptides from the perspectives of food material constraints, processing adaptability, multifunctional application, and cross-modal interaction while emphasizing the importance of utilizing computational technology. This review provides a reference for advancing the development and application of salty and salt-enhancing peptides as sodium substitutes in low-sodium food formulations.
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Peptídeos , Cloreto de Sódio na Dieta , Percepção Gustatória , Paladar , HumanosRESUMO
In this study, we inserted a dynamic chemical reaction system that can generate CO2 into Janus hydrogel (JH) to develop a multidimensional preservation platform that integrates hygroscopicity, antibacterial activity, and modified atmospheric capacity. The double gel system developed using sodium alginate/trehalose at a 1:1 ratio effectively encapsulated 90% of citric acid. Furthermore, CO2 loss was avoided by separately embedding NaHCO3/cinnamon essential oil and citric acid microcapsules into a gelatin pad to develop JH. Freeze-dried JH exhibited a porous and asymmetric structure, very strongly absorbing moisture, conducting water, and rapidly releasing CO2 and essential oils. Furthermore, when preserving various fruits and vegetables in practical settings, JH provided several preservation effects, including color protection, microbial inhibition, and antioxidant properties. Our study findings broaden the application of JH technology for developing chemical reaction systems, with the resulting JH holding substantial promise for cold chain logistics.
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Reduction of soluble U(VI) to insoluble U(IV) based on photocatalysts is a simple, environmentally friendly, and efficient method for treating radioactive wastewater. The present study involved the systematic comparison of the photoelectric properties of three metalloporphyrins with different metal centers and the synthesis of a novel porphyrin-based hydrogen-bonded organic framework (Ni-pHOF) photocatalyst by modulating the surface charge microenvironment in porphyrin for enhanced photocatalytic removal of U(VI) from wastewater. Compared to the metal-free HOF, the surface charge microenvironment around the Ni atom in Ni-pHOF accelerated the reduction kinetics of U(VI) under visible light illumination at the initial moment, showing a high removal rate, even in air. The removal rate of U(VI) from aqueous solution by Ni-pHOF can achieve over 98% in the presence of coexisting nonoxidizing cations and only decreased by less than 8% after five cycles, exhibiting high selectivity and good reusability. Furthermore, Ni-pHOF can remove 86.74% of U(VI) from real low-level radioactive wastewater after 120 min of illumination, showcasing practical application potential. Density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) spectra indicated that modulating the surface charge microenvironment in Ni-pHOF through porphyrin metallization is conducive to improving the charge separation efficiency, prompting more e- and â¢O2- to participate in the reduction reaction of U(VI). This work provides new insights into the metallization of porphyrin-based HOFs and paves a new way for the tailoring of porphyrin-based HOFs/COFs by modulating the surface charge microenvironment to achieve efficient recovery of U(VI) from real radioactive wastewater.
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The presence of carbonates or humic substances (HS) will significantly affect the species and chemical behavior of U(VI) in solution, but lacking systematic exploration of the coupling effect of carbonates and HS under near real environmental conditions at present. Herein, the sorption behavior of U(VI) on illite was systematically studied in the co-existence of carbonates and HS including both humic acid (HA) and fulvic acid (FA) by batch technique. The distribution coefficients (Kd) increased as function of time and temperature but decreased with increasing concentrations of initial U(VI), Ca2+, and Mg2+, as well as ion strength. At pH 2.0-10.5, the Kd values first increased rapidly and then decreased visibly, with its maximum value appearing at pH 5.0, owning to the changes in the interaction between illite and the dominant species of U(VI) from electrostatic attraction to electrostatic repulsion. The sorption was a heterogeneous, spontaneous, and endothermic chemical process, which could be well described by pseudo-second-order kinetic and Flory-Huggins isotherm models. When carbonates and HA/FA coexisted, the Kd values always increased first and then decreased as a function of pH, with the only difference for HA and FA being the key pH (pHkey) at which the promoting and inhibiting effects on the sorption of U(VI) onto illite undergo a transition. The carbonates and HS have a synergistic inhibitory effect on the U(VI) sorption onto illite at pH 7.8. FTIR and XPS spectra demonstrated that the hydroxyl groups on the illite surface and in the HS were involved in U(VI) sorption on illite in the presence of carbonates. These results provide valuable data for a deeper understanding of U(VI) migration in geological media.
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Carbonatos , Substâncias Húmicas , Minerais , Urânio , Adsorção , Carbonatos/química , Urânio/química , Minerais/química , Modelos Químicos , Benzopiranos/química , CinéticaRESUMO
AIM: Robotic-assisted pancreatectomy has been widely used. Organ-preserving pancreatectomy (OPP) and parenchymal-sparing pancreatectomy (PSP) has been gradually adopted for pancreatic benign or low-grade malignant tumors. This study aimed to evaluate the safety and efficacy of robotic-assisted OPP/PSP in our institute. METHODS: Patients undergoing robotic-assisted OPS/PSP at First Affiliated Hospital of Sun Yat-sen University between July 2015 and October 2021 were included in this study. The short-term and long-term outcomes of patients were retrospectively analyzed. RESULTS: Seventy-two patients were enrolled, including spleen-preserving distal pancreatectomy, central pancreatectomy, duodenum-preserving pancreatic head resection, and enucleation. Patients included were more likely to be young female (female: 46/72, median age: 47 years old). The median intraoperative blood loss and operation time was 50 ml and 255 min, respectively. Clinically relevant postoperative pancreatic fistula was 20.8% (grade B: 15/72, 20.8%; no grade C). The overall complication rate was 22.2% with the median postoperative length-of-stay of 8 days. At a median follow-up time of 28.5 months, the 5-year overall survival and recurrence-free survival rate were 100.0% and 100.0%, respectively. CONCLUSION: The short-term and long-term outcomes of patients receiving robotic-assisted OPP/PSP were acceptable. Robotic-assisted OPP/PSP was a feasible and safe technique for pancreatic benign or low-grade malignant lesions.
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Neoplasias , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Pessoa de Meia-Idade , Pancreatectomia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Pâncreas/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
Counter-gravity casting (CGC) aims to eliminate turbulent melt flow and defect formation during filling and subsequent solidification by pushing high-temperature melt into the mold cavity against gravity with regulated pressure. However, limited by the opaqueness of molten metals and the complexity of the CGC apparatus, it is extremely difficult to directly quantify the high-velocity mold filling and pressurized solidification in real-time. Here, we report the design and characterization of a CGC system capable of in situ monitoring of mold filling and subsequent solidification processes in the synchrotron beamlines by deploying a high-energy, high-speed synchrotron x-ray imaging technique. The high-velocity melt flow and dendrite growth during pressurized solidification have been quantified for systematical process parameter analysis by investigating time-resolved x-ray images of an exemplary Al-Cu alloy. The high-speed imaging results demonstrate that the in situ CGC system provides a useful way to better understand the fundamentals of mold filling, pressurized solidification, and experimental inputs for high-fidelity modeling in scientific and industrial applications.
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Aberrant A-to-I RNA editing, mediated by ADAR1 has been found to be associated with increased tumourigenesis and the development of chemotherapy resistance in various types of cancer. Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with a poor prognosis, and overcoming chemotherapy resistance poses a significant clinical challenge. This study aimed to clarify the roles of ADAR1 in tumour resistance to cisplatin in iCCA. We discovered that ADAR1 expression is elevated in iCCA patients, particularly in those resistant to cisplatin, and associated with poor clinical outcomes. Downregulation of ADAR1 can increase the sensitivity of iCCA cells to cisplatin treatment, whereas its overexpression has the inverse effect. By integrating RNA sequencing and Sanger sequencing, we identified BRCA2, a critical DNA damage repair gene, as a downstream target of ADAR1 in iCCA. ADAR1 mediates the A-to-I editing in BRCA2 3'UTR, inhibiting miR-3157-5p binding, consequently increasing BRCA2 mRNA and protein levels. Furthermore, ADAR1 enhances cellular DNA damage repair ability and facilitates cisplatin resistance in iCCA cells. Combining ADAR1 targeting with cisplatin treatment markedly enhances the anticancer efficacy of cisplatin. In conclusion, ADAR1 promotes tumour progression and cisplatin resistance of iCCA. ADAR1 targeting could inform the development of innovative combination therapies for iCCA.
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Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.