Clinical significance of RNA methylation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

PDM-SHD NFDM transmission with envelope-detection feedback polarization tracking and optical injection locking.

Nonlinear frequency division multiplexing (NFDM) systems, especially the eigenvalue communications have the potential to overcome the nonlinear Shannon capacity limit. However, the baud rate of eigenvalue communications is typically restricted to a few GBaud, making it challenging to mitigate laser frequency impairments such as the phase noise and frequency offset (FO) using digital signal processing (DSP) algorithms in intradyne detections (IDs). Therefore, we introduce the polarization division multiplexing-self-homodyne detection (PDM-SHD) into the NFDM link, which could overcome the impact of phase noise and FO by transmitting a pilot carrier originating from the transmitter laser to the receiver through the orthogonal polarization state of signal. To separate the signal from the carrier at the receiver, a carrier to signal power ratio (CSPR) unrestricted adaptive polarization controlling strategy is proposed and implemented by exploiting the optical intensity fluctuation of the light in a particular polarization rather than its direct optical power as the feedback. Optical injection locking (OIL) is used subsequently to amplify optical power of pilot carrier and mitigate the impact of signal-signal beat interference (SSBI). Additionally, the effects of cross-polarization modulation (XPolM) and modulation instability (MI) in long haul transmission are explored and inhibited. The results show that the tolerable FO range is about 3.5 GHz, which is 17 times larger than the ID one. When 16-amplitude phase shift keying (APSK) or 64-APSK constellations are used, identical Q-factor performance can be obtained by using distributed feedback (DFB, ∼10 MHz) laser, external cavity laser (ECL, ∼100kHz), or fiber laser (FL, ∼100 Hz), respectively, which demonstrates that our proposed PDM-SHD eigenvalue communication structure is insensitive to the laser linewidth. Under the impact of cycle slip, the Q-factor difference of 16-APSK signal between the ECL-ID system and ECL-SHD system can be up to 8.73 dB after 1500 km transmission.

Reset-free adaptive polarization controller on a silicon-photonic platform for a self-coherent communication system.

To give full play to the advantages of the self-coherent systems in the data center scene, the problem of the random walk of the polarization state of the delivered local oscillator must be solved. An adaptive polarization controller (APC) is an effective solution, with the characteristics of easy integration, low complexity, being reset-free, and so on. In this work, we experimentally demonstrated an endlessly APC based on a Mach-Zehnder interferometer on a silicon-photonic integrated circuit. The APC is thermally tuned with only two control electrodes. It endlessly stabilizes the arbitrary state of polarization (SOP) of the light to a state of equal power of the two orthogonal polarizations (X and Y). A polarization tracking speed of up to 800 rad/s is achieved.

HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis.

BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications.

RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies. Video Abstract.

Integrated communication and polarization sensing in self-homodyne coherent systems.

We propose and demonstrate an integrated polarization sensing technique by fully exploiting the adaptive polarization controller (APC) in a self-homodyne coherent (SHC) communication system. By analyzing the APC control signal, the input state of polarization (SOP) can be fully restored. The effect of the polarization tracking results on sensing accuracy is carefully studied in simulation to determine the acceptable SOP rotation speed. We experimentally restore the SOP rotation trajectory using an APC, conduct a comparison with a polarization analysis instrument, and verify its potential as a polarization measurement. Finally, without additional components or burdening digital signal processing (DSP), in-service detections of up to 400-Hz vibration and 2.4-nε micro-strain are achieved in the operated SHC system with 400-Gb/s DP-16QAM transmission.

The structure and phase of tau: from monomer to amyloid filament.

Tau is a microtubule-associated protein involved in regulation of assembly and spatial organization of microtubule in neurons. However, in pathological conditions, tau monomers assemble into amyloid filaments characterized by the cross-ß structures in a number of neurodegenerative diseases known as tauopathies. In this review, we summarize recent progression on the characterization of structures of tau monomer and filament, as well as the dynamic liquid droplet assembly. Our aim is to reveal how post-translational modifications, amino acid mutations, and interacting molecules modulate the conformational ensemble of tau monomer, and how they accelerate or inhibit tau assembly into aggregates. Structure-based aggregation inhibitor design is also discussed in the context of dynamics and heterogeneity of tau structures.

Airspeed-Aided State Estimation Algorithm of Small Fixed-Wing UAVs in GNSS-Denied Environments.

Aimed at improving the navigation accuracy of the fixed-wing UAVs in GNSS-denied environments, this paper proposes an algorithm of nongravitational acceleration estimation based on airspeed and IMU sensors, which use a differential tracker (TD) model to further supplement the effect of linear acceleration for UAVs under dynamic flight. We further establish the mapping relationship between vehicle nongravitational acceleration and the vehicle attitude misalignment angle and transform it into the attitude angle rate deviation through the nonlinear complementary filtering model for real-time compensation. It can improve attitude estimation precision significantly for vehicles in dynamic conditions. Furthermore, a lightweight complementary filter is used to improve the accuracy of vehicle velocity estimation based on airspeed, and a barometer is fused on the height channel to achieve the accurate tracking of height and the lift rate. The algorithm is actually deployed on low-cost fixed-wing UAVs and is compared with ACF, EKF, and NCF by using real flight data. The position error within 30 s (about 600 m flying) in the horizontal channel flight is less than 30 m, the error within 90 s (about 1800 m flying) is less than 50 m, and the average error of the height channel is 0.5 m. The simulation and experimental tests show that this algorithm can provide UAVs with good attitude, speed, and position calculation accuracy under UAV maneuvering environments.

New mechanism of FA in composted sludge inducing Cu fixation on Albite in open-pit mine soil.

Fulvic acid (FA), typical organic matter derived from humification process in composted sludge, possesses the potential to remediate mine soils contaminated by heavy metals. To understand the cooper (Cu) immobilizing process in open-pit mine soil induced by FA, changes of Cu speciation in mixture of open-pit mine soil and composted sludge was tracked over 180 days. It was observed that the organic-bound and residual fraction of Cu increased dramatically with the corresponding decrease of Fe/Mn oxide-bound Cu in the first 60 days, then the organic-bound fraction decreased to about its initial proportion during 60-120 days, while residual fraction still increased, and the proportion of residual Cu accounted for over 85% and became stable after 120 days. To reveal the mechanism of FA inducing Cu fixation on Albite which is the main phase of soil primary ore, two groups of Cu adsorption experiments with and without FA were designed. With the addition of FA, the adsorption capacity of Cu by Albite increased by 1.55 times and the content of residual Cu in Albite increased by 7.7 times. It was found that the Cu absorbed in smaller Albite particle induced by FA formed a secondary mineral--Chrysocolla, causing increase of residual fraction of Cu. These results revealed the mechanism: FA was absorbed on the surface of Albite after complexing with Cu ions in the solution, and then it induced Cu into the interlayer and pore channels of Albite. The Cu in the Albite was immobilized by forming Chrysocolla finally.

Introducing intrinsic disorder reduces electrostatic steering in protein-protein interactions.

Protein-protein interactions underlie many critical biology functions, such as cellular signaling and gene expression, in which electrostatic interactions can play a critical role in mediating the specificity and stability of protein complexes. A substantial portion of proteins are intrinsically disordered, and the influences of structural disorder on binding kinetics and thermodynamics have been widely investigated. However, whether the effect of electrostatic steering depends on structural disorder remains unexplored. In this work, we addressed the consequence of introducing intrinsic disorder in the electrostatic steering of the E3/Im3 complex using molecular dynamics simulation. Our results recapitulated the experimental observations that the responses of stability and kinetics to salt concentration for the ordered E3/Im3 complex were larger than those for the disordered E3/Im3 complex. Mechanistic analysis revealed that the native contact interactions involved in the encounter state and the transition state were essentially identical for both ordered and disordered E3. Therefore, the observed difference in electrostatic steering between ordered E3 and disordered E3 may result from their difference in conformation rather than their difference in binding mechanism. Because charged residues are frequently involved in protein-protein interactions, our results suggest that increasing structural disorder is expected to generally modulate the effect of electrostatic steering.

All-optical polarization split of the signal and LO for a bi-directional self-homodyne coherent system.

In this Letter, we propose a cost-efficient bi-directional (BiDi) polarization-multiplexed self-homodyne coherent detection (SHCD) system, in which only one fiber link and one adaptive polarization controller (APC) are required. By employing the correlation of the state of polarization (SOP) between the upstream and downstream light, one APC is capable of stabilizing SOPs of the counterpropagating waves at the same time. The signal and local oscillator (LO) can be optically split by a polarization beam splitter (PBS), relaxing pressure of the digital signal processing (DSP) and simplifying the coherent receiver. The impact induced by polarization cross talk and delay mismatch is collectively investigated by theoretical analysis and simulation. Finally, the proposed scheme is experimentally verified through 120 Gbit/s 16-quadrature amplitude modulation (16-QAM) transmission, achieving a satisfying laser-linewidth tolerance of 10 MHz and a polarization rotation tolerance of up to 45 rad/s.

Establishment of reference intervals of complete blood count for twin pregnancy.

BACKGROUND: Twin pregnancy poses a high risk, and its incidence has increased in recent years. Establishment of reference intervals of complete blood count (CBC) for women with twin pregnancies during pregnancy may aid in the prognosis of adverse outcomes. METHODS: The incidence of complications and the intensity associated with adverse outcomes were analyzed in 1153 cases of twin pregnancy. A total of 253 cases in the twin pregnancy reference cohort were screened from all candidates after complications and adverse pregnancy outcomes were excluded. Complete blood count data were collected during the mid- and late-term of pregnancy and analyzed using SPSS to establish the reference intervals for peripheral blood in twin pregnancy. RESULTS: Premature rupture of the membrane and pelvic inflammatory disease were highly positively correlated with adverse outcomes, with OR values of 3.31 and 3.81, respectively. Within the interval population with normal outcomes, red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), and platelet (PLT) values were lower in twin-pregnant women during gestation than in healthy nulligravida women, but the levels of white blood cells (WBC), neutrophils (NEU), and the NEU% increased, especially in the mid-term. The reference intervals of late-term pregnancy were validated using 20 twin pregnancies samples, and then utilized to determine the distinctive CBC characteristics in preterm birth (PTB) pregnancy. Absolute WBC and NEU values increased in PTB pregnancy based on our established reference intervals, which suggests that these may might be prognostic indicators of this adverse outcome. CONCLUSION: Establishing the reference interval of blood cell-related indicators of normal twin pregnancy is helpful for the monitoring and prognosis of gestation.

Impact of hyperglycaemia on complications in patients who had a stroke after thrombolysis.

BACKGROUND: We sought to investigate whether admission hyperglycaemia is associated with complications in patients who had an acute ischaemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator and, if so, whether complications during hospitalisation modify the effect of hyperglycaemia on 3-month poor outcome after thrombolysis. METHODS: Patients who were diagnosed with AIS after thrombolysis between July 2016 and January 2019 were enrolled in this study. Five prespecified complications, including infections, brain oedema, deep vein thrombosis (DVT), haemorrhagic transformation (HT) and gastrointestinal bleeding, were recorded during hospitalisation. RESULTS: Of 388 patients, 143 (36.86%) presented with hyperglycaemia. Patients with hyperglycaemia were more likely to experience one or more complications than patients without hyperglycaemia. After adjustment for potential confounders, hyperglycaemia was associated with brain oedema (OR 2.39; 95% CI 1.08 to 5.30), HT (OR 2.16, 95% CI 1.06 to 4.41), symptomatic intracerebral haemorrhage (sICH) (OR 7.32, 95% CI 2.35 to 22.80) and gastrointestinal bleeding (OR 3.62; 95% CI 1.93 to 6.80), but was not linked to infections (OR 1.48, 95% CI 0.76 to 2.9) and DVT (OR 0.60, 95% CI 0.23 to 1.5). Additional adjustment for the complications in the clinical outcome analysis, done to assess these complications as an intermediate in the pathway from admission hyperglycaemia to clinical outcome, did not substantially change the model (all p for interaction >0.05). CONCLUSION: Hyperglycaemia is an independent predictor of complications following stroke after thrombolysis, especially for brain oedema, gastrointestinal bleeding, HT and sICH. Complications during hospitalisation did not modify the effect of hyperglycaemia on the poor outcome at 3 months in ischaemic stroke.

Comparison of Transcatheter Mitral-Valve Repair and Surgical Mitral-Valve Repair in Elderly Patients with Mitral Regurgitation.

PURPOSE: To summarize comparative studies of MitraClip versus surgical repair in typical, real-world elderly patients with severe mitral regurgitation (MR) and analyze the safety and effectiveness of these therapeutic options. METHODS: PubMed, Medline, Embase, and Cochrane Controlled Register of Trials (CENTRAL) were searched for comparative studies of transcatheter mitral-valve repair (TMVR) versus surgical mitral-valve repair (SMVR) in elderly patients with severe MR from January 2000 to June 2020. Statistical pooling for incidence estimates was performed according to a random-effects model with generic inverse-variance weighting, computing risk estimates with 95% confidence intervals (CIs), using RevMan 5.3. RESULTS: A total of 14 reports comparing MitraClip with SMVR, enrolling 3355 patients with severe MR, were included in this study. Mean age, Logistic EuroSCORE, and incidence of diabetes mellitus (DM) were significantly higher in the MitraClip group, except the rate of patients with New York Heart Association (NYHA) class of >II and mean value of ejection fraction (EF). The arithmetic mean of freedom from acute mobility was similar. The 2 groups had equal all-cause mortality at 30 days, but different at 1 year (14% versus 9%) and 3 years in 7 studies (37% versus 25%). The freedom from recurrent MR ≥3+ was 88% and 97.3% at 30 days, 76.0% and 90.0% at 1 year, and 79% and 95% at 3 years in the MitraClip and surgical repair group, respectively. CONCLUSION: Although MitraClip is safe and effective in selected high-risk patients, the surgery may be the only gold standard for "gray" patients. Further studies are needed to determine whether MitraClip should be recommended.

Development of a droplet digital PCR method for detection of Streptococcus agalactiae.

BACKGROUND: Streptococcus agalactiae (GBS) is the causative pathogen of puerperal sepsis in pregnant women and pneumonia, sepsis and meningitis in infants. Infection of GBS is responsible for the increased morbidity in pregnant women and the elderly, and bring challenges to clinical diagnosis and treatment. However, culture-based approaches to detect S.agalactiae is time-consuming with limited sensitivity. Besides, real-time quantitative PCR demands expensive instruments with tedious steps. Thus, we aim to establish a new detection method for more accurate and rapid detection of S.agalactiae. RESULTS: The ddPCR primer targeted the CpsE gene showed better amplified efficiency in the reaction. The limit of detection for GBS DNA with ddPCR was able to reach 5 pg/µL. Moreover, no positive amplified signals could be detected in the reactions which served 11 non-GBS strains DNA as templates. Furthermore, the coefficient of variation of this method was 4.5%, indicating excellent repeatability of ddPCR assay. CONCLUSIONS: In our study, ddPCR was performed as a rapid detection of S.agalactiae with high sensitivity and specificity. This technique can promote the accuracy of the diagnosis of GBS infection and provide a scientific basis for clinical treatment.

Linezolid and the risk of lactic acidosis: Data mining and analysis of the FDA Adverse Event Reporting System.

WHAT IS KNOWN AND OBJECTIVE: Lactic acidosis (LA) is a rare but potentially lethal side effect of linezolid (LZD). However, limited by the study population, the number of patients with LA is insufficient to summarize all the clinical characteristics and risk factors. METHODS: We evaluated the association between LZD and LA using the reporting odd ratio (ROR) for mining the adverse event report signals in the FDA Adverse Event Reporting System database from January 2013 to December 2019. RESULTS AND DISCUSSION: There were 6218 reports of LZD as the primary suspected drug or secondary suspected drug, of which 275 (4.42%) reports were of LA. The ROR of LA with the use of LZD was 39.976 (95% CI 35.365-45.189). In the age composition of patients, elderly individuals (aged ≥60 years) accounted for the higher proportion, 42.54% (n = 117). LA usually occurred two weeks after LZD administration (n = 33). LZD was the unique suspected drug, accounting for 37.45% (n = 103) of all reports of LA. The drug with the most frequent occurrence of combination with LZD was 'meropenem' and 'warfarin'. WHAT IS NEW AND CONCLUSIONS: The ROR of LA caused by LZD was very high, and the number of reports about LA caused by other antibiotics was significantly different from that of LA caused by LZD. The drug combined with LZD did not seem to affect the occurrence of LA, and the high occurrence of warfarin in the reports deserves the attention of doctors.

Novel chitosan-ethylene glycol hydrogel for the removal of aqueous perfluorooctanoic acid.

It is urgent to explore an effective removal method for perfluorooctanoic acid (PFOA) due to its recalcitrant nature. In this study, a novel chitosan-based hydrogel (CEGH) was prepared with a simple method using chitosan and ethylene glycol through a repeated freezing-thawing procedure. The adsorption of PFOA anions to CEGH agreed well to the Freundlich-Langmuir model with a maximum adsorption capacity as high as 1275.9 mg/g, which is higher than reported values of most adsorbents for PFOA. The adsorption was influenced by experimental conditions. Experimental results showed that the main removal mechanism was the ionic hydrogen bond interaction between carbonyl groups (COO-) of PFOA and protonated amine (NH+) of the CEGH adsorbent. Therefore, CEGH is a very attractive adsorbent that can be used to remove PFOA from water in the future.

Development of a promising PPAR signaling pathway-related prognostic prediction model for hepatocellular carcinoma.

The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status. Following, a prognostic prediction model of HCC was developed by using the random survival forest method and Cox regression analysis. Significant difference in survival outcome, immune landscape, drug sensitivity and pathological features were observed between patients with different prognosis. Additionally, decision tree and nomogram models were adopted to optimize the prognostic prediction model. Furthermore, the robustness of the model was verified through single-cell RNA-sequencing data. Collectively, this study systematically elucidated that the PPAR signaling pathway-related prognostic model has good predictive efficacy for patients with HCC. These findings provide valuable insights for further research on personalized treatment approaches for HCC.

Emerging function of main RNA methylation modifications in the immune microenvironment of digestive system tumors.

Digestive system tumors have been reported in more than 25% of all cancer cases worldwide, bringing a huge burden on the healthcare system. RNA methylation modification-an important post-transcriptional modification-has become an active research area in gene regulation. It is a dynamic and reversible process involving several enzymes, such as methyltransferases, demethylases, and methylation reader proteins. This review provides insights into the role of three major methylation modifications, namely m6A, m5C, and m1A, in the development of digestive system tumors, specifically in the development of tumor immune microenvironment (TIME) of these malignancies. Abnormal methylation modification affects immunosuppression and antitumor immune response by regulating the recruitment of immune cells and the release of immune factors. Understanding the mechanisms by which RNA methylation regulates digestive system tumors will be helpful in exploring new therapeutic targets.

Risk of immune system and skin and subcutaneous tissue related adverse events associated with oxaliplatin combined with immune checkpoint inhibitors: a pharmacovigilance study.

Background: Few studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs). Methods: We evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients. Results: There were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex-mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678. Conclusion: Type II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.