Parental histone transfer caught at the replication fork.

In eukaryotes, DNA compacts into chromatin through nucleosomes1,2. Replication of the eukaryotic genome must be coupled to the transmission of the epigenome encoded in the chromatin3,4. Here we report cryo-electron microscopy structures of yeast (Saccharomyces cerevisiae) replisomes associated with the FACT (facilitates chromatin transactions) complex (comprising Spt16 and Pob3) and an evicted histone hexamer. In these structures, FACT is positioned at the front end of the replisome by engaging with the parental DNA duplex to capture the histones through the middle domain and the acidic carboxyl-terminal domain of Spt16. The H2A-H2B dimer chaperoned by the carboxyl-terminal domain of Spt16 is stably tethered to the H3-H4 tetramer, while the vacant H2A-H2B site is occupied by the histone-binding domain of Mcm2. The Mcm2 histone-binding domain wraps around the DNA-binding surface of one H3-H4 dimer and extends across the tetramerization interface of the H3-H4 tetramer to the binding site of Spt16 middle domain before becoming disordered. This arrangement leaves the remaining DNA-binding surface of the other H3-H4 dimer exposed to additional interactions for further processing. The Mcm2 histone-binding domain and its downstream linker region are nested on top of Tof1, relocating the parental histones to the replisome front for transfer to the newly synthesized lagging-strand DNA. Our findings offer crucial structural insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.

A tri-functional amino acid enables mapping of binding sites for posttranslational-modification-mediated protein-protein interactions.

Posttranslational modification (PTM), through the recruitment of effector proteins (i.e., "readers") that signal downstream events, plays key roles in regulating a variety of cellular processes. To understand how a PTM is recognized, it is necessary to find its readers and, importantly, the location of the binding pockets responsible for PTM recognition. Although various methods have been developed to identify PTM readers, it remains a challenge to directly map the PTM-binding regions, especially for intrinsically disordered domains. Here, we demonstrate a photo-crosslinkable, clickable, and cleavable tri-functional amino acid, ADdis-Cys, that when coupled with mass spectrometry (ADdis-Cys-MS) can not only identify PTM readers from complex proteomes but also simultaneously map their PTM-recognition modules. Using ADdis-Cys-MS, we successfully identify the binding sites of several reader-PTM interactions, among which we discover human C1QBP as a histone chaperone. This robust method should find wide applications in examining other histone or non-histone PTM-mediated protein-protein interactions.

The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.

Altered corticalfunctional networks in Wilson's disease: A resting-state electroencephalogram study.

The neuropsychiatric symptoms are common in Wilson's disease (WD) patients. However, it remains unclear about the associated functional brain networks. In this study, source localization-based functional connectivity analysis of close-eye resting-state electroencephalography (EEG) were implemented to assess the characteristics of functional networks in 17 WD patients with neurological involvements and 17 healthy controls (HCs). The weighted phase-lag index (wPLI) was subsequently calculated in source space across five different frequency bands and the resulting connectivity matrix was transformed into a weighted graph whose structure was measured by five graphical analysis indicators, which were finally correlated with clinical scores. Compared to HCs, WD patients revealed disconnected sub-networks in delta, theta and alpha bands. Moreover, WD patients exhibited significantly reduced global clustering coefficients and small-worldness in all five frequency bands. In WD group, the severity of neurological symptoms and structural brain abnormalities were significantly correlated with disrupted functional networks. In conclusion, our study demonstrated that functional network deficits in WD can reflect the severity of their neurological symptoms and structural brain abnormalities. Resting-state EEG may be used as a marker of brain injury in WD.

Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

The value of gadolinium-enhanced MRI in predicting the development of sudden hearing loss into Ménière's disease.

OBJECTIVE: To compare the clinical features of sudden hearing loss (SHL) in patients with and without endolymphatic hydrops (EH), and to investigate the association between SHL with EH and Ménière's disease (MD). METHODS: The clinical data of 63 SHL patients with first symptoms were evaluated retrospectively. Patients were separated into two groups based on the results of gadolinium-enhanced magnetic resonance imaging: EH and non-EH groups. Independent sample t-test and U-test were used to compare groups for continuous variables, and the chi-squared test, corrected chi-squared test and Bonferroni correction test were used to compare groups for binary and ordinal variables. The binary logistic regression model was utilised for univariate and multivariate analysis of follow-up patient prognosis. RESULTS: The EH and non-EH groups contained 32 and 31 patients, respectively. The EH group had a higher prevalence of low-tone descending hearing loss. Fifty-one patients were followed for more than 2 years. In the EH group, 11 and 15 patients were diagnosed with sudden sensorineural hearing loss (SSNHL) and MD, respectively, while in the non-EH group, 24 patients were diagnosed with SSNHL and only one with MD. EH, low-tone descending hearing loss and vertigo were risk factors for the diagnosis of MD in a subgroup univariate regression analysis of patients experiencing SHL. EH was found to be a risk factor for the progression of SHL into MD in a multifactor regression analysis. CONCLUSIONS: Patients with SHL who have EH are more likely to present with low-tone descending hearing loss. EH is a risk factor for the subsequent development of MD.

Genetic liability to higher frailty index may increase the risk of ophthalmic disease.

PURPOSE: Frailty and age-related eye diseases are common in older people; however, whether there is a causal link remains unknown. We aimed to explore the causal associations between the frailty index (FI) and ophthalmic traits and identify modifiable mediators. METHODS: Linkage disequilibrium score regression and two-sample Mendelian randomization were applied to identify genetic correlations and causal associations between FI and ophthalmic traits. Summary data for FI was obtained from a genome-wide association study that included 175,226 individuals of European ancestry. Summary-level statistics for ophthalmic traits were obtained from relative GWASs. Summary-level data for cardiovascular risk factors, inflammatory biomarkers, and the central nervous system were used to identify the possible mediators. RESULTS: FI had a significant genetic correlation with 10 ophthalmic traits. Per SD increment of FI, the odds ratio was 1.329 (95% CI, 1.123, 1.573; P = 9.5 × 10-4) for cataracts, 1.825 (95% CI, 1.115, 2.986; P = 0.016) for keratitis, 1.798 (95% CI, 1.039, 3.11; P = 0.036) for disorders of vitreous body and 1.478 (95% CI, 1.005, 2.173; P = 0.046) for disorders of sclera, cornea, iris and ciliary body. The MR effect estimates of FI on ophthalmic traits were attenuated after adjusting for mental disorders, type 2 diabetes, triglyceride, and interleukin-8 (IL-8) levels. CONCLUSION: This study reports a genetic correlation and causal association between FI and ophthalmic traits, in which mental disorders, type 2 diabetes, triglycerides, and IL-8 may play a mediating role. These findings highlight a possible method to reduce the risk of FI-related ophthalmic diseases.

Coefficient of spatial variance of choroidal thickness on swept-source optical coherence tomography in healthy eyes.

PURPOSE: This study aims to introduce the coefficient of spatial variance of choroidal thickness to describe the choroidal variation and investigate its associated factors in healthy eyes. METHODS: This retrospective cross-sectional study included 1031 eyes from 1031 subjects who received a swept-source optical coherence tomography examination. The mean choroidal thickness in the macular 6 × 6 mm region and 900 subregions of 0.2 × 0.2 mm were computed using the embedded algorithm. Before analysis, potential segmentation and magnification errors were corrected. The coefficient of spatial variance was defined as the standard deviation divided by the mean (multiplied by 100%) of the choroidal thicknesses across 900 grids. Potential factors associated with the coefficient of spatial variance were assessed using multiple linear regression. RESULTS: The mean choroidal thickness of the entire 6 × 6 mm macular region was 204.50 ± 72.88 µm. The mean coefficient of spatial variance was 26.58 ± 8.24%, ranging from 11.00 to 61.58%. Statistical analysis revealed that the means choroidal thickness (ß = - 0.08, R2 = 0.42, p < 0.001) and anterior chamber depth (ß = - 2.39, R2 = 0.05, p = 0.06) were associated with the coefficient of spatial variance. CONCLUSION: Our study first incorporated the coefficient of spatial variance to represent the spatial variation of the choroidal thickness and observed that the greater thinning of the choroid is correlated with a more pronounced spatial variation.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Genetic liability to multi-site chronic pain increases the risk of cardiovascular disease.

BACKGROUND: Observational studies have shown associations between multi-site chronic pain (MCP) and cardiovascular disease. However, it remains unclear whether these associations are causal. Therefore, this study aimed to assess the causal associations between MCP and cardiovascular disease and identify possible mediators between them. METHODS: A two-sample Mendelian randomisation analysis was applied in this study. The summary data for MCP were obtained from a genome-wide association study that included 387 649 individuals from the UK Biobank, whereas summary-level data for cardiovascular disease and its subtypes were obtained from relevant genome-wide association studies. Finally, summary-level data for common cardiovascular risk factors and inflammatory biomarkers were leveraged to identify possible mediators. RESULTS: Genetic liability to multi-site chronic pain is associated with higher risks for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), and stroke, with a combined odds ratio (OR) of 1.537 (per site increment in MCP; 95% confidence interval [CI]: 1.271-1.858; P=0.0001) for CAD, 1.604 (95% CI: 1.277-2.014; P=0.0005) for MI, 1.722 (95% CI: 1.423-2.083; P<0.00001) for HF, and 1.332 (95% CI: 1.093-1.623; P=0.00001) for stroke. Genetic liability to MCP was found to be associated with mental disorders, smoking initiation, physical activity, BMI, and lipid metabolites. Multivariable Mendelian randomisation suggested a mediating role for mental disorders, smoking initiation, physical activity, and BMI in the relationship between multi-site chronic pain and cardiovascular disease. CONCLUSIONS: Our findings provide new insights into the role of multi-site chronic pain in cardiovascular disease. Additionally, we identified several modifiable risk factors for reducing cardiovascular disease.

Selective anatomical catheter ablation of left atrial ganglionated plexus for vasovagal syncope: Left superior and right anterior ganglionated plexus ablation.

BACKGROUND: Vasovagal syncope (VVS) is one of the most common causes of syncope. Traditional treatment has not achieved satisfactory results. The purpose of this study was to assess the feasibility and efficacy of selective anatomical catheter ablation of left atrial ganglionated plexus (GP) as a therapeutic strategy for the patients of symptomatic VVS. METHODS: A total of 70 patients with at least once recurrent syncopal episode of VVS with a positive head-up tilt test were enrolled. They were divided into GP ablation group and control group. Patients in GP ablation group received anatomical catheter ablation of left superior ganglionated plexus (LSGP) and right anterior ganglionated plexus (RAGP). Patients in the control group were guideline-directed conventional therapy. The primary endpoint was VVS recurrences. The secondary endpoint was the recurrence of syncope and prodrome events. RESULTS: There were no statistical differences in clinical characteristics between the ablation group (n = 35) and the control group (n = 35). Over a follow-up of 12 months, the ablation group had significantly lower syncope recurrence compared with the control group (5.7% vs. 25.7%, p = .02), and the ablation group had significantly lower syncope and prodrome recurrence compared with the control group (11.4% vs. 51.4%, p < .001). In GP ablation, 88.6% of the patients showed significant vagal response during LSGP ablation, and 88.6% of the patients showed significantly increased heart rate during RAGP ablation. CONCLUSIONS: For patients with recurrent VVS, selective anatomical catheter ablation of LSGP and RAGP is superior to conventional therapy in reducing syncope recurrence.

Intracardiac echocardiography is a safe and effective alternative to transesophageal echocardiography for left atrial appendage thrombus evaluation at the time of atrial fibrillation ablation: The ICE-TEE study.

BACKGROUND: Intracardiac echocardiography (ICE) technology has been increasingly accepted as an integral part of atrial fibrillation (AF) ablation procedures. It is still unknown whether ICE can routinely replace transesophageal echocardiography (TEE) for routine thrombus screening in non-selective AF patients. OBJECTIVE: To assess whether ICE can routinely replace TEE in screening for left atrial (LA)/left atrial appendage (LAA) thrombus in general patients undergoing catheter ablation for AF. METHODS: A total of 2003 consecutive patients undergoing AF ablation were included. 1155 patients (ICE group) received intra-procedural ICE examination for LA/LAA thrombus screening, while 848 patients (TEE group) received pre-procedure TEE examination. The incidence of thrombus, peri-procedure complications, and hospital efficiency were assessed. RESULTS: The LA and LAA were adequately visualized in all patients. Five patients in the ICE group and 15 patients in the TEE group were found to have LAA thrombus. The incidence of major periprocedural thrombo-embolic events was comparable between two groups (0.2% vs. 0.1%, p = .76), none were due to undetected LA/LAA thrombus. Other major periprocedural complications occurred at similar rates in both groups, while post-procedure fever was less common in the ICE group (12.7% vs. 17.4%, p < .001). Procedure times and hospital length of stay were both shorter in the ICE group (142 min [87-197 min] vs. 150 min [95-205 min], and 3[2-4] day vs. 4[3-5] day, respectively, both p < .001). CONCLUSIONS: ICE can replace TEE for atrial thrombus screening in AF patients undergoing ablation without increased complications. An "ICE replacing TEE" workflow can also reduce the incidence of postoperative fever and improve hospital efficiency.

Spatiotemporal distribution of migraine in China: analyses based on baidu index.

BACKGROUND: In recent years, innovative approaches utilizing Internet data have emerged in the field of syndromic surveillance. These novel methods aim to aid in the early prediction of epidemics across various scenarios and diseases. It has been observed that these systems demonstrate remarkable accuracy in monitoring outbreaks even before they become apparent in the general population. Therefore, they serve as valuable complementary tools to augment existing methodologies. In this study, we aimed to investigate the spatiotemporal distribution of migraine in China by leveraging Baidu Index (BI) data. METHODS: Migraine-related BI data from January 2014 to December 2022 were leveraged, covering 301 city-level areas from 31 provincial-level regions by using the keyword "migraine ()". Prevalence data from the Global Burden of Disease study (GBD) were attracted to ensure the reliability of utilizing migraine-related BI data for research. Comprehensive analytical methods were then followed to investigate migraine's spatiotemporal distribution. The Seasonal-Trend decomposition procedure based on Loess (STL) was used to identify the temporal distribution. Spatial distribution was explored using the Getis-Ord Gi* statistic, standard deviation ellipse analysis, Moran's Index, and Ordinary Kriging. The top eight migraine-related search terms were analyzed through the Demand Graph feature in the Baidu Index platform to understand the public's concerns related to migraine. RESULTS: A strong association was observed between migraine-related BI and the prevalence data of migraine from GBD with a Spearman correlation coefficient of 0.983 (P = 4.96 × 10- 5). The overall trend of migraine-related BI showed a gradual upward trend over the years with a sharp increase from 2017 to 2019. Seasonality was observed and the peak period occurred in spring nationwide. The middle-lower reaches of the Yangtze River were found to be hotspots, while the eastern coastal areas had the highest concentration of migraine-related BI, with a gradual decrease towards the west. The most common search term related to migraine was "How to treat migraine quickly and effectively ()". CONCLUSIONS: This study reveals important findings on migraine distribution in China, underscoring the urgent need for effective prevention and management strategies.

Development of prediction models to estimate extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia: a cross-sectional study.

BACKGROUND: To develop prediction models for extubation time and midterm recovery time estimation in ophthalmic patients who underwent general anesthesia. METHODS: Totally 1824 ophthalmic patients who received general anesthesia at Joint Shantou International Eye Center were included. They were divided into a training dataset of 1276 samples, a validation dataset of 274 samples and a check dataset of 274 samples. Up to 85 to 87 related factors were collected for extubation time and midterm recovery time analysis, respectively, including patient factors, anesthetic factors, surgery factors and laboratory examination results. First, multiple linear regression was used for predictor selection. Second, different methods were used to develop predictive models for extubation time and midterm recovery time respectively. Finally, the models' generalization abilities were evaluated using a same check dataset with MSE, RMSE, MAE, MAPE, R-Squared and CCC. RESULTS: The fuzzy neural network achieved the highest R-Squared of 0.956 for extubation time prediction and 0.885 for midterm recovery time, and the RMSE value was 6.637 and 9.285, respectively. CONCLUSION: The fuzzy neural network developed in this study had good generalization performance in predicting both extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia. TRIAL REGISTRATION: This study is prospectively registered in the Chinese Clinical Trial Registry, registration number: CHiCRT2000036416, registration date: August 23, 2020.

Effect of common ions aging treatment on adsorption of phosphate onto and control of phosphorus release from sediment by lanthanum-modified bentonite.

The objective of this work was to explore the influence of combined aging treatment using Na+, Ca2+, Cl-, HCO3- and SO42- on the adsorption of phosphate (HiPO4i-3) onto and the restraint of internal phosphorus (P) migration into overlying water (OW) by lanthanum modified bentonite (LMB). To achieve this aim, the adsorption characteristics and mechanisms of HiPO4i-3 onto the raw and aged LMBs (named as R-LMB and A-LMB, respectively) were comparatively studied, and the effects of R-LMB and A-LMB treatments (addition and capping) on the migration of P from sediment to OW were comparatively investigated. The results showed that the combined aging treatment of R-LMB with Na+, Ca2+, Cl-, HCO3- and SO42- inhibited the adsorption of HiPO4i-3. Similar to R-LMB, the precipitation of HiPO4i-3 with La3+ to form LaPO4 and the ligand exchange between CO32- and HiPO4i-3 to form the inner-sphere lanthanum-phosphate complexes are the important mechanisms for the HiPO4i-3 uptake by A-LMB. The R-LMB addition and capping can be effective in the suppression of endogenous P release to OW under hypoxia conditions. The inactivation of diffusive gradient in thin film-unstable P (DGT-UP) and potentially mobile P (PM-P) in sediment acted as a key role in the restraint of internal P release to OW by the R-LMB addition, and the immobilization of DGT-UP and PM-P in the topmost sediment played a key role in the interception of endogenous P migration into OW by the R-LMB capping. Although the Na+/Ca2+/Cl-/HCO3-/SO42- combined aging treatment had a certain negative effect on the efficiencies of LMB addition and capping to hinder the liberation of P from sediment into OW, the A-LMB addition and capping still can be effective in the control of sediment internal phosphorus pollution to a certain degree. The results of this work indicate that LMB has a high potential to be used as a capping/amendment material to control internal phosphorus pollution.

The effects of online peer-facilitated learning and distributed pair programming on students' learning.

The COVID-19 pandemic has forced universities and schools around the world to adopt online learning. Teachers may wonder if their students can attain satisfactory learning performance in an online learning environment without teachers' on-the-spot attention. In order to develop students' skills in programming, promote their enjoyment of learning and intention to learn to program, the researchers integrated two innovative teaching approaches, using online peer-facilitated learning and distributed pair programming, and investigated the effects of these on students' online learning performance. This study conducted an experiment that included 128 undergraduates from four class sections of Department of Finance. Thus, the experimental design in this research was a 2 (Peer-facilitated learning vs. non-peer-facilitated learning) × 2 (Distributed pair programming vs. non-distributed pair programming) factorial pretest/post-test design. The participants in this research mainly consisted of four classes of students from a non-computer or information department who took a compulsory course on programming design.' Both quantitative and qualitative data were collected in this study. According to the results, the peer-facilitated learning group exhibited significantly better development of programming skills, enjoyment of learning, and intention to learn, than the non-peer-facilitated learning group. However, expected effects of enhancing the learning of the students in this study who received the distributed pair programming were not found. The design of online pedagogy can be a reference for online educators. The implications of applying online peer-facilitated learning and distributed pair programming to support students' learning and the design of online programming courses are discussed.

Photo-Cross-Linking To Delineate Epigenetic Interactome.

Covalent modifications of DNA and histones are key cellular epigenetic marks to regulate gene functions. Most of these epigenetic marks are added or removed by corresponding enzymes known as writers and erasers, whose catalytic activities normally rely on the presence of cellular metabolites as cofactors. Epigenetic marks can either directly alter the chromatin structure and dynamics through changing the intra-/internucleosomal histone-histone and histone-DNA interactions or recruit readers that further bring in other proteins with chromatin-modifying/remodeling activities to reshape the local and regional chromatin organization. In these two ways, epigenetic modifications modulate diverse DNA-templated processes, such as gene transcription, DNA replication, and DNA damage repair. Therefore, elucidation of the regulatory mechanisms and biological significance of epigenetic marks requires the identification and characterization of the protein-protein, protein-nucleic acid, and protein-small molecule interactions that control the underlying epigenetic processes. Here, we review the recent advances in using photo-cross-linking strategies to interrogate the epigenetic interactome, focusing on the protein-protein interactions mediated by epigenetic marks in histone tails. We also discuss future directions of developing photo-cross-linking-based tools and methods toward the investigation of the binding events in nucleosomal/chromatinic contexts, and toward the in situ capture of the epigenetic interactome in live cells or even organisms.

Dual-mode detection of dopamine based on 0D/2D/2D CuInS2/ZnS quantum dot-black phosphorous nanosheet-TiO2 nanosheet nanocomposites.

In this work, we designed new dual-mode "turn-on" electrochemical (EC) and photoelectrochemical (PEC) sensors for the detection of dopamine (DA) based on 0D/2D/2D CuInS2/ZnS quantum dot (QD)-black phosphorous nanosheet (BPNS)-TiO2 nanosheet (TiO2NS) nanocomposites. QDs can not only improve the photocurrent of the developed PEC sensors, but also provide the electrochemical signal in the EC detection. BPNSs as p-type semiconductor with high conductive properties work as electron acceptors and are utilized to improve the sensitivity of the DA PEC and EC sensors. Under irradiation of visible light or the applied voltage, DA is both excited and releases electrons, realizing "turn-on" detection. The PEC sensors have a linear range of 0.1-100 µM with a lower detection limit of 0.028 µM. For the EC detection, BPNSs can accelerate electron transfer which attribute to its excellent conductivity. In the range of 1-200 µM, the working curve of DA detection by the EC sensors was established and the detection limit is 0.88 µM. Comparing the two methods, the PEC sensors have a lower detection limit, and the EC sensors have a wider monitoring range. The dual-mode sensors of EC and PEC pave an effective way for the detection in biological and medical fields.

Robotic versus laparoscopic major hepatectomy for hepatocellular carcinoma: short-term outcomes from a single institution.

BACKGROUND: Currently, an increasing number of robotic major hepatectomies for hepatocellular carcinoma (HCC) are being performed. Despite the advantages of robotic surgery over laparoscopic procedures, studies comparing robotic with laparoscopic major hepatectomy in terms of short-term results remain scarce. This study was performed to compare robotic major hepatectomy and laparoscopic major hepatectomy in terms of their intraoperative and postoperative results. METHODS: Data regarding demographics and intraoperative and postoperative results of 131 patients undergoing robotic or laparoscopic major hepatectomy between January 2017 and March 2022 were retrieved from their medical records and compared between the two types of surgery. RESULTS: Between January 2017 and March 2022, 44 robotic major hepatectomies and 87 laparoscopic major hepatectomies were performed at the Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital. Patients undergoing robotic major hepatectomy were not significantly different from those undergoing laparoscopic major hepatectomy in terms of age (P = 0.397), sex (P = 0.624), body mass index (BMI) (P = 0.118), alpha-fetoprotein (AFP) (P = 0.09), tumor size (P = 0.176), cirrhosis (P = 0.384), fatty liver (P = 0.162), preoperative antiviral treatment (P = 0.934), hepatitis B virus (HBV) DNA (P = 0.646) and operation type (P = 0.054). Robotic major hepatectomy was associated with a longer operation time (median: 255.5 versus 206.8 min; P < 0.001) and less estimated blood loss (median: 118.9 versus 197.0 ml; P = 0.002) than laparoscopic major hepatectomy. However, robotic major hepatectomy was not significantly different from laparoscopic major hepatectomy regarding length of postoperative hospital stay (P = 0.849), open conversion (P = 0.077), ICU stay (P = 0.866), postoperative massive abdominal bleeding (P = 1.00), portal vein thrombosis (P = 1.00), abdominal infection (P = 1.00), pulmonary infection (P = 1.00), pulmonary embolism (P = 1.00), cardiac complications (P = 1.00), liver failure (P = 1.00), kidney failure (P = 1.00), biliary leak (P = 1.00), positive resection margin (P = 1.00), 30-day mortality (P = 1.00) and 90-day mortality (P = 1.00). CONCLUSIONS: Robotic major hepatectomy was as effective as laparoscopic surgery in terms of intraoperative and postoperative results but took longer and could more efficiently control intraoperative blood loss.

Integrating online meta-cognitive learning strategy and team regulation to develop students' programming skills, academic motivation, and refusal self-efficacy of Internet use in a cloud classroom.

With the development of technology and demand for online courses, there have been considerable quantities of online, blended, or flipped courses designed and provided. However, in the technology-enhanced learning environments, which are also full of social networking websites, shopping websites, and free online games, it is challenging to focus students' attention and help them achieve satisfactory learning performance. In addition, the instruction of programming courses constantly challenges both teachers and students, particularly in online learning environments. To overcome and solve these problems and to facilitate students' learning, the researchers in this study integrated two teaching approaches, using meta-cognitive learning strategy (MCLS) and team regulation (TR), to develop students' regular learning habits and further contribute to their programming skills, academic motivation, and refusal self-efficacy of Internet use, in a cloud classroom. In this research, a quasi-experiment was conducted to investigate the effects of MCLS and TR adopting the experimental design of a 2 (MCLS vs. non-MCLS) × 2 (TR vs. non-TR) factorial pre-test/post-test. In this research, the participants consisted of four classes of university students from non-information or computer departments enrolled in programming design, a required course. The experimental groups comprised three of the classes, labelled as G1, G2, and G3. G1 concurrently received both the online MCLS and TR intervention, while G2 only received the online MCLS intervention, and G3 only received the online TR intervention. Serving as the control group, the fourth class (G4) received traditional teaching. This study investigated the effects of MCLS, TR, and their combination, on improving students' programming skills, academic motivation, and refusal self-efficacy of Internet use in an online computing course. According to the results, students who received online TR significantly enhanced their programming design skills and their refusal self-efficacy of Internet use a cloud classroom. However, the expected effects of MCLS on developing students' programming skills, academic motivation, and refusal self-efficacy of Internet use were not found in this study. The teaching strategy of integrating MCLS and TR in an online programming course in this study can serve as a reference for educators when conducting online, blended, or flipped courses during the COVID-19 pandemic.