A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy.

Intrinsic and acquired drug resistance and induction of secondary malignancies limit successful chemotherapy. Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment-induced mutations, targeting TLS is an attractive avenue for improving chemotherapeutics. However, development of small molecules with high specificity and in vivo efficacy for mutagenic TLS has been challenging. Here, we report the discovery of a small-molecule inhibitor, JH-RE-06, that disrupts mutagenic TLS by preventing recruitment of mutagenic POL ζ. Remarkably, JH-RE-06 targets a nearly featureless surface of REV1 that interacts with the REV7 subunit of POL ζ. Binding of JH-RE-06 induces REV1 dimerization, which blocks the REV1-REV7 interaction and POL ζ recruitment. JH-RE-06 inhibits mutagenic TLS and enhances cisplatin-induced toxicity in cultured human and mouse cell lines. Co-administration of JH-RE-06 with cisplatin suppresses the growth of xenograft human melanomas in mice, establishing a framework for developing TLS inhibitors as a novel class of chemotherapy adjuvants.

Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

Remarkable heat conduction mediated by non-equilibrium phonon polaritons.

Surface waves can lead to intriguing transport phenomena. In particular, surface phonon polaritons (SPhPs), which result from coupling between infrared light and optical phonons, have been predicted to contribute to heat conduction along polar thin films and nanowires1. However, experimental efforts so far suggest only very limited SPhP contributions2-5. Through systematic measurements of thermal transport along the same 3C-SiC nanowires with and without a gold coating on the end(s) that serves to launch SPhPs, here we show that thermally excited SPhPs can substantially enhance the thermal conductivity of the uncoated portion of these wires. The extracted pre-decay SPhP thermal conductance is more than two orders of magnitude higher than the Landauer limit predicted on the basis of equilibrium Bose-Einstein distributions. We attribute the notable SPhP conductance to the efficient launching of non-equilibrium SPhPs from the gold-coated portion into the uncoated SiC nanowires, which is strongly supported by the observation that the SPhP-mediated thermal conductivity is proportional to the length of the gold coating(s). The reported discoveries open the door for modulating energy transport in solids by introducing SPhPs, which can effectively counteract the classical size effect in many technologically important films and improve the design of solid-state devices.

Conformation-dependent lesion bypass of bulky arylamine-dG adducts generated from 2-nitrofluorene in epigenetic sequence contexts.

Sequence context influences structural characteristics and repair of DNA adducts, but there is limited information on how epigenetic modulation affects conformational heterogeneity and bypass of DNA lesions. Lesions derived from the environmental pollutant 2-nitrofluorene have been extensively studied as chemical carcinogenesis models; they adopt a sequence-dependent mix of two significant conformers: major groove binding (B) and base-displaced stacked (S). We report a conformation-dependent bypass of the N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene (dG-FAF) lesion in epigenetic sequence contexts (d[5'-CTTCTC#G*NCCTCATTC-3'], where C# is C or 5-methylcytosine (5mC), G* is G or G-FAF, and N is A, T, C or G). FAF-modified sequences with a 3' flanking pyrimidine were better bypassed when the 5' base was 5mC, whereas sequences with a 3' purine exhibited the opposite effect. The conformational basis behind these variations differed; for -CG*C- and -CG*T-, bypass appeared to be inversely correlated with population of the duplex-destabilizing S conformer. On the other hand, the connection between conformation and a decrease in bypass for flanking purines in the 5mC sequences relative to C was more complex. It could be related to the emergence of a disruptive non-S/B conformation. The present work provides novel conformational insight into how 5mC influences the bypass efficiency of bulky DNA damage.

Stable Interstrand Cross-Links Generated from the Repair of 1,N6-Ethenoadenine in DNA by α-Ketoglutarate/Fe(II)-Dependent Dioxygenase ALKBH2.

DNA cross-links severely challenge replication and transcription in cells, promoting senescence and cell death. In this paper, we report a novel type of DNA interstrand cross-link (ICL) produced as a side product during the attempted repair of 1,N6-ethenoadenine (εA) by human α-ketoglutarate/Fe(II)-dependent enzyme ALKBH2. This stable/nonreversible ICL was characterized by denaturing polyacrylamide gel electrophoresis analysis and quantified by high-resolution LC-MS in well-matched and mismatched DNA duplexes, yielding 5.7% as the highest level for cross-link formation. The binary lesion is proposed to be generated through covalent bond formation between the epoxide intermediate of εA repair and the exocyclic N6-amino group of adenine or the N4-amino group of cytosine residues in the complementary strand under physiological conditions. The cross-links occur in diverse sequence contexts, and molecular dynamics simulations rationalize the context specificity of cross-link formation. In addition, the cross-link generated from attempted εA repair was detected in cells by highly sensitive LC-MS techniques, giving biological relevance to the cross-link adducts. Overall, a combination of biochemical, computational, and mass spectrometric methods was used to discover and characterize this new type of stable cross-link both in vitro and in human cells, thereby uniquely demonstrating the existence of a potentially harmful ICL during DNA repair by human ALKBH2.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Modification of the electrokinetic motion of microalgae through light illumination for viability assessment.

The viability detection of microalgae with the electrokinetic (EK) technique shows vast applications in the biology and maritime industry. However, due to the slight variations in the EK properties between alive and dead microalgae cells, the accuracy and practicability of this technique is limited. In this paper, the light illumination pretreatment was conducted to modify the EK velocity of microalgae for enhancing the EK difference. The effects of the illumination time and light color on the EK velocities of Chlorella vulgaris and Isochrysis galbana were systematically measured, and the EK differences between alive and dead cells were calculated and compared. The results indicate that under light illumination, the photosynthesis of the alive cells leads to the amplification of the zeta potential, leading toward increase in the EK difference along with the illumination time. By using light with different color spectra to treat the microalgae, it was found that the EK difference changes with the light color according to the following order: white light > red light > blue light > green light. The difference in EK potential with exposure to white light treatment surpasses over 10-fold in comparison to those without such treatment. The light pretreatment technique, as illustrated in this study, offers an advantageous strategy to enhance the EK difference between living and dead cells, proving beneficial in the field of microalgae biotechnology.

Reexamination of Damping in Sliding Friction.

Friction is responsible for about one-third of the primary energy consumption in the world. So far, a thorough atomistic understanding of the frictional energy dissipation mechanisms is still lacking. The Amontons' law states that kinetic friction is independent of the sliding velocity while the Prandtl-Tomlinson model suggests that damping is proportional to the relative sliding velocity between two contacting objects. Through careful analysis of the energy dissipation process in atomic force microscopy measurements, here we propose that damping force is proportional to the tip oscillation speed induced by friction. It is shown that a physically well-founded damping term can better reproduce the multiple peaks in the velocity-dependent friction force observed in both experiments and molecular dynamics simulations. Importantly, the analysis gives a clear physical picture of the dynamics of energy dissipation in different friction phases, which provides insight into long-standing puzzles in sliding friction, such as velocity weakening and spring-stiffness-dependent friction.

The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

An immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment.

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. CONCLUSIONS: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Heat Flow Guiding and Modulation by Kinks in a Silicon Nanoribbon.

Tailoring heat flow in solids has profound implications for the innovation of functional thermal devices. However, the current methods face technological challenges related to system complexity, material stability, and operating temperature. In this study, we demonstrated efficient heat flow modulation in a single material without a phase transition, using a simple and entirely material-independent strategy, kinked nanostructure patterning, at near-ambient temperature. By carefully controlling the kink arm length and kink angle of the Si nanoribbons, we achieved a thermal conductivity modulation of up to ∼20%. Our theoretical modeling showed that this modulation results from the competing roles of phonon backscattering and open view channels on heat transport. We also build a regime map based on the existence of an open view channel and provide concrete design guidelines for thermal conductivity modulation considering the kink angle and arm length. This study opens up new opportunities for efficient heat flow manipulation through nanostructure patterning.

Guided Polaritons along the Forbidden Direction in MoO3 with Geometrical Confinement.

Highly anisotropic materials show great promise for spatial control and the manipulation of polaritons. In-plane hyperbolic phonon polaritons (HPhPs) supported by α-phase molybdenum trioxide (MoO3) allow for wave propagation with a high directionality due to the hyperbola-shaped isofrequency contour (IFC). However, the IFC prohibits propagations along the [001] axis, hindering information or energy flow. Here, we illustrate a novel approach to manipulating the HPhP propagation direction. We experimentally demonstrate that geometrical confinement in the [100] axis can guide HPhPs along the forbidden direction with phase velocity becoming negative. We further developed an analytical model to provide insights into this transition. Moreover, as the guided HPhPs are formed in-plane, modal profiles were directly imaged to further expand our understanding of the formation of HPhPs. Our work reveals a possibility for manipulating HPhPs and paves the way for promising applications in metamaterials, nanophotonics, and quantum optics based on natural van der Waals materials.

Recent advances in multimode microfluidic separation of particles and cells.

Microfluidic separation of particles and cells is crucial to lab-on-a-chip applications in the fields of science, engineering, and industry. The continuous-flow separation methods can be classified as active or passive depending on whether the force involved in the process is externally imposed or internally induced. The majority of current separations have been realized using only one of the active or passive methods. Such a single-mode process is usually limited to one-parameter separation, which often becomes less effective or even ineffective when dealing with real samples because of their inherent heterogeneity. Integrating two or more separation methods of either type has been demonstrated to offer several advantages like improved specificity, resolution, and throughput. This article reviews the recent advances of such multimode particle and cell separations in microfluidic devices, including the serial-mode prefocused separation, serial-mode multistage separation, and parallel-mode force-tuned separation.

Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study).

BACKGROUND: Small-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10-15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels. METHODS: This is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). DISCUSSION: The addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy. TRIAL REGISTRATION: This study protocol was prospectively registered on June 17, 2021. CLINICALTRIALS: gov Identifier: NCT04933175 .

Surface charging and electrophoretic behavior of conductive polymer micro-droplets in conductive polymer liquid solutions.

This study investigates the surface charging and electrophoretic motion of polyethylene glycol-rich (PEG-rich) micro-droplets in dextran-rich solutions or dextran-rich micro-droplets in PEG-rich solutions. The electrophoretic velocities of the droplets were measured in a centimeter-sized chamber under an optical microscope. It was found that the direction of electrophoretic motion of both the PEG-rich droplets and dextran-rich droplets is opposite to the applied electric field, meaning that both the PEG-rich droplets and dextran-rich droplets are negatively charged. The electrophoretic velocity is independent of droplet size but proportional to the electric field strength. Increasing the NaCl concentration reduces the electrophoretic velocity of PEG-rich droplets and increases it for dextran-rich droplets, suggesting different surface charge changes due to ion affinity. The charge densities and velocities are affected by the PEG and dextran mass fractions. Physical models for droplet surface charging under different conditions were proposed to explain the experimental results.

Experimental Evidence of Superdiffusive Thermal Transport in Si0.4Ge0.6 Thin Films.

Superdiffusive thermal transport represents a unique phenomenon in heat conduction, which is characterized by a size (L) dependence of thermal conductivity (κ) in the form of κ ∝ Lß with a constant ß between 0 and 1. Although superdiffusive thermal transport has been theoretically predicted for SiGe alloys, direct experimental evidence is still lacking. Here, we report on a systematic experimental study of the thickness-dependent thermal conductivity of Si0.4Ge0.6 thin films grown by molecular beam epitaxy. The cross-plane thermal conductivity of Si0.4Ge0.6 thin films spanning a thickness range from 20 to 1120 nm was measured in the temperature range 120-320 K via a differential three-omega method. Results show that the thermal conductivity follows a consistent κ ∝ t0.26 power law with the film thickness (t) at different temperatures, providing direct experimental evidence that alloy-scattering dominated thermal transport in SiGe is superdiffusive.

Network pharmacology analysis and experimental validation of Anemarrhenae Rhizoma in treating Alzheimer's disease. / çŸ¥æ¯æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— ç½‘ç»œè¯ç†å­¦ç ”ç©¶åŠå®žéªŒéªŒè¯.

OBJECTIVES: To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease (AD). METHODS: The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods, the protein-protein interaction (PPI) network was constructed and the core targets were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriching analysis was performed. The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines (LCL) were constructed and an in vitro cell model of LCL-SKNMC was established. MTT and CCK-8 methods were used to quantify SKNMC/LCL cells, 2 ´, 7 ´-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect reactive oxygen species (ROS), and immunofluorescence staining was used to detect the generation of Aß1-42 in a co-cultured model. Western blotting was used to detect protein expression in the co-culture model. The lifespan of N2 nematodes was observed under oxidative stress, normal state, and heat stress; ROS generated by N2 nematodes was detected by DCFH-DA probes. The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay, and Aß deposition in the pharynx was detected by Thioflavin S staining. RESULTS: Through network pharmacology, 15 potential active ingredients and 103 drug-disease targets were identified. PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin, Akt1, tumor necrosis factor, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mammalian target of rapamycin (mTOR), amyloid precursor protein (APP) and other related targets. KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease, endocrine resistance, insulin resistance; and neuroactive ligand-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, calcium signaling pathway, AGE-RAGE signaling pathway in diabetes complications, neurotrophic factor signaling pathway and others. The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aß1-42 (both P<0.01), inhibit the expression of ß-secretase 1 (BACE1), APP and Aß1-42 proteins (all P<0.05), up-regulate the expression of p-PI3K/PI3K, p-AKT/AKT, p-GSK3ß/GSK3ß in SKNMC cells (all P<0.05). The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C. elegans under stress and normal conditions, reduced the accumulation of ROS and the toxicity of Aß deposition. CONCLUSIONS: Anemarrhenae Rhizoma may reduce the production of Aß in AD and inhibit its induced oxidative stress, which may be achieved by regulating the PI3K/Akt/GSK-3ß pathway.

LncRNA MAPKAPK5_AS1 facilitates cell proliferation in hepatitis B virus -related hepatocellular carcinoma.

We explored the biological role of long non-coding RNA (lncRNA) MAPKAPK5_AS1 (MAAS) and the mechanism of its differential expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Differentially expressed lncRNAs in HBV-related HCC were determined using bioinformatics analysis. Gain-of-function experiments were conducted to evaluate the effect of MAAS on cell proliferation. A xenograft model was established for in vivo experiments. Dual-luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation, and methylated RNA immunoprecipitation were performed to elucidate the underlying molecular mechanisms. MAAS was upregulated in HBV-related HCC cancerous tissues and its high expression was closely related to the poor survival probability of patients. Functional assays revealed that MAAS overexpression facilitated the proliferation of HBV+HCC cells in vitro and in vivo. Mechanistically, MAAS promoted the MYC proto-oncogene (c-Myc)-induced transcriptional activation of cyclin-dependent kinase 4 (CDK4), CDK6, and S-phase kinase associated protein 2 via stabilizing c-Myc protein, thereby facilitating G1/S transition. The latter contributed to the paradoxical proliferation of HBV+HCC cells. Although MAAS was upregulated in HBV-related HCC cancerous tissues, it was highly expressed in M2 macrophages, a major phenotype of tumor-associated macrophages in HBV-related HCC, instead of in HBV+HCC cells. HBeAg, an HBV-associated antigen, further elevated the MAAS level in M2 macrophages by enhancing the methyltransferase-like 3-mediated N6-methyladenosine modification of MAAS. The increased MAAS in the M2 macrophages was then transferred to HBV+HCC cells through the M2 macrophage-derived exosomes, promoting cell proliferation. Our findings show that HBV+HCC cell-secreted HBeAg upregulates MAAS expression in M2 macrophages by affecting its m6A modification. The upregulated MAAS is then transferred to HBV+HCC cells via exosomes, facilitating the proliferation of HBV+HCC cells by targeting c-Myc.

Dynamic Observation of Retinal Response to Pressure Elevation in a Microfluidic Chamber.

Dynamic observation of cell and tissue responses to elevated pressure could help our understanding of important physiological and pathological processes related to pressure-induced injury. Here, we report on a microfluidic platform capable of maintaining a wide range of stable operating pressures (30 to 200 mmHg) while using a low flowrate (2-14 µL/h) to limit shear stress. This is achieved by forcing flow through a porous resistance matrix composed of agarose gel downstream of a microfluidic chamber. The flow characteristics were investigated and the permeabilities of the agarose with four different concentrations were extracted, agreeing well with results found in the literature. To demonstrate the capability of the device, we measured the change in intracellular Ca2+ levels of retinal ganglion cells in whole mouse retina in response to pressure. The onset of enhanced pressure results in, on average, an immediate 119.16% increase in the intracellular Ca2+ levels of retinal ganglion cells. The demonstrated microfluidic platform could be widely used to probe cell and tissue responses to elevated pressure.

Size-dependent electrophoretic motion of polystyrene particles at polyethylene glycol-dextran interfaces.

Currently, there is very limited information on the electrophoretic behavior of particles at a liquid-liquid interface formed by two conducting liquid solutions. Here, electrophoretic velocities of polystyrene particles at a polyethylene glycol (PEG)-dextran (DEX) interface were investigated in this paper. Experimental results show that the particle at the interface moves in the opposite direction to the applied electric field, with a velocity much lower than that in the PEG-rich phase and a litter larger than that in the DEX-rich phase. Similarly to the movement in Newtonian fluids, the velocity increases linearly with the increase in the applied electric field. Different to particle electrophoresis in Newtonian fluids, the velocities of the particles at the PEG-DEX interface increase linearly with the decrease in particle's diameters, implying a possible size-based particle differentiation at an interface.