Disrupted inter-brain synchronization in the prefrontal cortex between adolescents and young adults with gaming disorders during the real-world cooperating video games.

BACKGROUND: Gaming disorder (GD) and hazardous gaming (HG) have a high incidence among adolescents and young adults and have caused various negative consequences. Interpersonal interaction deficits are closely related to GD and HG, however, the underlying brain mechanisms are still unclear. METHODS: The current study recruited 46 healthy subjects and 32 subjects with GD/HG. Gaming time and frequency, gaming disorder risks, life events, strengths, and difficulties were measured with scales. Subjects were randomly paired into 12 HC-HC dyads, 15 GD/HG-HC dyads, and 7 GD/HG-GD/HG dyads and in pairs completed a real-world cooperating video game - "Tied Together" with functional near-infrared spectroscopy hyperscanning recording in the prefrontal cortex. The inter-brain synchronization in each region of the PFC between dyads was calculated by wavelet to transform coherence to measure brain-to-brain synchronization. RESULTS: We found subjects with GD/HG reported higher risks of gaming. The highest IBS in the left dorsolateral prefrontal cortex significantly decreased in the GD/HG-HC and GD/HG-GD/HG dyads compared with healthy controls. A decreasing highest IBS of the left dlPFC was related to a decreasing level of peer problems. LIMITATIONS: We declare limitations of age gaps of samples, undistinguishing GD from HG, use of sub-samples, and the broad concept of interpersonal interaction. CONCLUSIONS: The current study found a decreased highest IBS in the left dlPFC among adolescents and young adults with gaming diseases. It may provide new prevention and treatment insights into gaming disorders targeting disrupted interpersonal interaction.

Cyano-Rich g-C3 N4 in Photochemistry: Design, Applications, and Prospects.

Cyano-rich g-C3 N4 materials are widely used in various fields of photochemistry due to the very powerful electron-absorbing ability and electron storage function of cyano, as well as its advantages in improving light absorption, adjusting the energy band structure, increasing the polarization rate and electron density in the structure, active site concentration, and promoting oxygen activation ability. Notwithstanding, there is yet a huge knowledge break in the design, preparation, detection, application, and prospect of cyano-rich g-C3 N4 . Accordingly, an overall review is arranged to substantially comprehend the research progress and position of cyano-rich g-C3 N4 materials. An overall overview of the current research position in the synthesis, characterization (determination of their location and quantity), application, and reaction mechanism analysis of cyano-rich g-C3 N4 materials to provide a quantity of novel suggestions for cyano-modified carbon nitride materials' construction is provided. In view of the prevailing challenges and outlooks of cyano-rich g-C3 N4 materials, this paper will purify the growth direction of cyano-rich g-C3 N4 , to achieve a more in-depth exploration and broaden the applications of cyano-rich g-C3 N4 .

Study on the reversal of epileptic drug resistance by tetramethylpyrazine in combination with carbamazepine through modulation of P-Glycoprotein expression in rat brain microvessel endothelial cell.

The purpose of this study was to detect the changes of P-Glycoprotein (P-GP) expression in rat brain microvessel endothelial cell line RBE4 after the action of Tetramethylpyrazine (TMP) on Carbamazepine (CBZ), so as to clarify the potential mechanism of TMP combined with CBZ against intractable epilepsy drug resistance. The RBE4 cell line was utilized for in vitro analysis. Cells were divided into control, CBZ, and CBZ-TMP group. The expression of P-GP was assessed using Western blot and reverse transcription polymerase chain reaction (RT-PCR). Intracellular concentration of CBZ was measured through high-performance liquid chromatography (HPLC). The differential expression of mRNA was evaluated by RNA sequencing. The intracellular concentration of CBZ in the CBZ-TMP group was significantly higher than that in other groups. The expression of P-GP in the CBZ group was significantly higher than that in the control group, while in the CBZ&TMP group, it was significantly lower than that in the other groups. Comparative analysis also revealed some differentially expressed genes. Compared with the CBZ group, FAM106A, SLC3A2, TENM2, etc. were upregulated most significantly in the CBZ&TMP group. ZBTB10, WDR7, STARD13, etc. were downregulated most significantly. Results suggest that TMP increases the intracellular concentration of CBZ, downregulates the expression of P-GP increased by CBZ, and modulates related cellular metabolism and signaling pathways, thus reversing the drug resistance mechanism of intractable epilepsy, providing a theoretical basis for the combination of traditional Chinese medicine and antiepileptic drugs.

MCM10, a potential diagnostic, immunological, and prognostic biomarker in pan-cancer.

Microchromosome maintenance (MCM) proteins are a number of nuclear proteins with significant roles in the development of cancer by influencing the process of cellular DNA replication. Of the MCM protein family, MCM10 is a crucial member that maintains the stability and extension of DNA replication forks during DNA replication and is significantly overexpressed in a variety of cancer tissues, regulating the biological behaviour of cancer cells. But little is understood about MCM10's functional role and regulatory mechanisms in a range of malignancies. We investigate the impact of MCM10 in human cancers by analyzing data from databases like the Gene Expression Profiling Interaction Analysis (GEPIA2), Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), among others. Possible relationships between MCM10 and clinical staging, diagnosis, prognosis, Mutation burden (TMB), microsatellite instability (MSI), immunological checkpoints, DNA methylation, and tumor stemness were identified. The findings demonstrated that MCM10 expression was elevated in the majority of cancer types and was connected to tumor dryness, immunocytic infiltration, immunological checkpoints, TMB and MSI. Functional enrichment analysis in multiple tumors also identified possible pathways of MCM10 involvement in tumorigenesis. We also discovered promising MCM10-targeting chemotherapeutic drugs. In conclusion, MCM10 may be a desirable pan-cancer biomarker and offer fresh perspectives on cancer therapy.

Lower synaptic density associated with gaming disorder: an 18F-SynVesT-1 PET imaging study.

Background: Internet gaming disorder (IGD) is an ideal model to study the mechanisms underlying synaptic deficits in addiction as it eliminates the confounding effects of substance use. Synaptic loss and deficits are hypothesised to underlie the enduring maladaptive behaviours and impaired cognitive function that contribute to IGD. Aims: This study aimed to determine whether subjects with IGD have lower synaptic density than control subjects and the relationship between synaptic density and IGD severity. Methods: Eighteen unmedicated subjects diagnosed with current IGD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and 16 demographically matched healthy controls (HCs) participated in the study and underwent 18F-labelled difluoro-analogue of UCB-J (18F-SynVesT-1) positron emission tomography scans to assess the density of synaptic vesicle glycoprotein 2A (SV2A). The Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), Barratt Impulsiveness Scale Version 11 (BIS-11), Stroop Colour-Word Test (SCWT), stop-signal paradigms and N-back tasks were administered to all subjects. Results: Patients with IGD had significantly higher scores on the IGDS9-SF, HAMD, HAMA and BIS-11 than HCs. HCs performed better on the two-back and SCWT tests as well as in terms of stop-signal reaction times (SSRTs) in the stop-signal paradigms than patients with IGD. Lower uptake was found in the bilateral putamen, right pregenual anterior cingulate cortex and Rolandic operculum of patients with IGD compared with HCs. Furthermore, in the IGD group, IGDS9-SF scores and daily gaming hours were negatively correlated with the standardised uptake value ratios of 18F-SynVesT-1 in the bilateral putamen. Longer SSRTs were significantly associated with lower SV2A density in the right pregenual anterior cingulate cortex and right Rolandic operculum. Conclusions: The in vivo results in this study suggest that lower synaptic density contributes to the severity and impairments in inhibitory control of IGD. These findings may provide further incentive to evaluate interventions that restore synaptic transmission and plasticity to treat IGD.

Associations of polyunsaturated fatty acids with cardiovascular disease and mortality: a study of NHANES database in 2003-2018.

BACKGROUND: This study was to explore the association between dietary polyunsaturated fatty acids (PUFAs) consumption and cardiovascular diseases (CVDs), all-cause mortality, and CVD-specific mortality. METHODS: This retrospective cohort study extracted demographic and clinical data of 38,838 adult participants from the National Health and Nutrition Examination Survey (NHANES) database in 2003-2018. We explored the association between octadecadienoic acid (ODA), octadecatrienoic acid (ALA), octadecatetraenoic acid (ODTA), eicosatetraenoic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) and different CVDs using weighted univariate and multivariate logistic regression analyses with odds ratio (OR) and 95% confidence interval (CI). The PUFAs were divided into four levels according to the quartiles (≤ Q1, Q1 to Q2, Q1 to Q2, > Q3). Weighted univariate and multivariate COX regression analyses with hazard ratio (HR) and 95% CI were used for exploring the association between PUFAs and all-cause mortality, CVD-specific mortality and other cause-specific mortality. RESULTS: During the follow-up, a total of 4,908 (9.12%) eligible participants died. The results showed that after adjusting for covariates, ODTA intake was related to low odds of coronary heart disease (CHD) [OR = 0.75, 95%CI: (0.64-0.88)]. Q1-Q2 quartile of ALA [OR = 0.81, 95%CI: (0.66-0.99)] and Q2-Q3 quartile of DPA [OR = 0.78, 95%CI: (0.62-0.99)] intakes were linked to low odds of heart attack, and > Q3 quartile of ODA intake was associated with low odds of congestive heart failure (CHF) [OR = 0.66, 95%CI: (0.49-0.90)] and stroke [OR = 0.65, 95%CI: (0.47-0.90)]. Q2-Q3 quartile of DPA intake was linked to low odds of angina [OR = 0.76, 95%CI: (0.58-0.99)]. Higher ALA intake was associated with a lower risk of all-cause mortality [Q2-Q3: HR = 0.86, 95%CI: (0.74-0.99); > Q3: HR = 0.76, 95%CI: (0.63-0.91)]. Additionally, Q2-Q3 quartile of ALA, Q1-Q2 quartile of AA and DPA intakes were respectively related to a low risk of CVD-specific mortality, while that > Q3 quartile of ALA related to that of mortality by other causes. CONCLUSION: Our study found that PUFAs were associated with different CVDs, and higher ALA intake was related to lower risk of all-cause mortality. Ensuring adequate intake of PUFAs was beneficial to the health and may decrease the risk of mortality.

Development of miniature base editors using engineered IscB nickase.

As a miniature RNA-guided endonuclease, IscB is presumed to be the ancestor of Cas9 and to share similar functions. IscB is less than half the size of Cas9 and thus more suitable for in vivo delivery. However, the poor editing efficiency of IscB in eukaryotic cells limits its in vivo applications. Here we describe the engineering of OgeuIscB and its corresponding ωRNA to develop an IscB system that is highly efficient in mammalian systems, named enIscB. By fusing enIscB with T5 exonuclease (T5E), we found enIscB-T5E exhibited comparable targeting efficiency to SpG Cas9 while showing reduced chromosome translocation effects in human cells. Furthermore, by fusing cytosine or adenosine deaminase with enIscB nickase, we generated miniature IscB-derived base editors (miBEs), exhibiting robust editing efficiency (up to 92%) to induce DNA base conversions. Overall, our work establishes enIscB-T5E and miBEs as versatile tools for genome editing.

Deep neural network to differentiate internet gaming disorder from healthy controls during stop-signal task: a multichannel near-infrared spectroscopy study.

Internet Gaming Disorder (IGD), as one of worldwide mental health issues, leads to negative effects on physical and mental health and has attracted public attention. Most studies on IGD are based on screening scales and subjective judgments of doctors, without objective quantitative assessment. However, public understanding of internet gaming disorder lacks objectivity. Therefore, the researches on internet gaming disorder still have many limitations. In this paper, a stop-signal task (SST) was designed to assess inhibitory control in patients with IGD based on prefrontal functional near-infrared spectroscopy (fNIRS). According to the scale, the subjects were divided into health and gaming disorder. A total of 40 subjects (24 internet gaming disorders; 16 healthy controls) signals were used for deep learning-based classification. The seven algorithms used for classification and comparison were deep learning algorithms (DL) and machine learning algorithms (ML), with four and three algorithms in each category, respectively. After applying hold-out method, the performance of the model was verified by accuracy. DL models outperformed traditional ML algorithms. Furthermore, the classification accuracy of the two-dimensional convolution neural network (2D-CNN) was 87.5% among all models. This was the highest accuracy out of all models that were tested. The 2D-CNN was able to outperform the other models due to its ability to learn complex patterns in data. This makes it well-suited for image classification tasks. The findings suggested that a 2D-CNN model is an effective approach for predicting internet gaming disorder. The results show that this is a reliable method with high accuracy to identify patients with IGD and demonstrate that the use of fNIRS to facilitate the development of IGD diagnosis has great potential.

Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing.

The type V-F CRISPR-Cas12f system is a strong candidate for therapeutic applications due to the compact size of the Cas12f proteins. In this work, we identify six uncharacterized Cas12f1 proteins with nuclease activity in mammalian cells from assembled bacterial genomes. Among them, OsCas12f1 (433 aa) from Oscillibacter sp. and RhCas12f1 (415 aa) from Ruminiclostridium herbifermentans, which respectively target 5' T-rich Protospacer Adjacent Motifs (PAMs) and 5' C-rich PAMs, show the highest editing activity. Through protein and sgRNA engineering, we generate enhanced OsCas12f1 (enOsCas12f1) and enRhCas12f1 variants, with 5'-TTN and 5'-CCD (D = not C) PAMs respectively, exhibiting much higher editing efficiency and broader PAMs, compared with the engineered variant Un1Cas12f1 (Un1Cas12f1_ge4.1). Furthermore, by fusing the destabilized domain with enOsCas12f1, we generate inducible-enOsCas12f1 and demonstate its activity in vivo by single adeno-associated virus delivery. Finally, dead enOsCas12f1-based epigenetic editing and gene activation can also be achieved in mammalian cells. This study thus provides compact gene editing tools for basic research with remarkable promise for therapeutic applications.

Decreased inter-brain synchronization in the right middle frontal cortex in alcohol use disorder during social interaction: An fNIRS hyperscanning study.

BACKGROUND: Alcohol use disorder (AUD) is a widespread mental disorder and has thrust a heavy burden on the health system all over the world. Social cognition and function are reported to be impaired in AUD, but its neural mechanism is rarely investigated. The current study attempts to fill this gap. METHODS: 28 subjects with AUD and 36 healthy controls (HC) were recruited in this study and were paired into 14 AUD dyads and 18 HC dyads. The drinking problems, depression, anxiety, and impulsivity of subjects were measured. Each dyad completed cooperation and competition tasks with simultaneous frontal functional near-infrared spectroscopy (fNIRS) hyperscanning recording. The inter-brain synchronization (IBS) in the frontal cortex was calculated for each dyad and compared between AUD and HC. The significantly altered IBS in AUD was correlated with clinical measures to explore possible influencing factors. RESULTS: The IBS in the right middle frontal cortex was significantly decreased in AUD under both cooperation (t = -2.257, P = 0.028) and competition (t = -2.488, P = 0.016) task. The IBS during the cooperation task in the right middle frontal cortex in AUD was negatively correlated with non-planning impulsivity (r = -0.673, P = 0.006). LIMITATIONS: This study used cross-sectional data, which limited the causal inference. The synchronization between other brain regions besides the frontal cortex should be further explored in patients with AUD. CONCLUSION: The current study could provide new insights into the neural mechanism of social dysfunction in AUD and facilitate clinical intervention in future practice.

Changes of internet behavior of adolescents across the period of COVID-19 pandemic in China.

During the COVID-19 pandemic, internet use and gaming of adolescents had been elevated. On the one hand, internet use and gaming in the period was a good approach to killing quarantined time. However, the increased use of the internet and game of adolescents may also increase the risk of internet addiction. This study aimed to describe the internet behavior changes of adolescents and to understand the impact of clinical features on internet addiction after the adolescents back to school in COVID-19 period. We conducted a cross-sectional cohort study using data collected through online investigation in China. Six hundred and twenty-five adolescents completed the online survey. Results indicated that internet addiction, having gaming use behaviors, Strengths and Difficulties Questionnaire (SDQ) Conduct subscale scores and the SDQ Prosocial subscale scores before the COVID-19 outbreak were significant in predicting the internet addiction after the adolescents back to school. The proportion of internet addiction and gaming behaviors among adolescents in China was changed across the COVID-19 pandemic. Clinical features before the COVID-19 pandemic could predict Internet addiction risk after the adolescents back to school.

Super-strong and high-performance electrical film heater derived from silver nanowire/aligned bacterial cellulose film.

High-performance electrical Joule heaters with high mechanical properties, low driving voltage, rapid response, and flexibility are highly desirable for portable thermal management. Herein, by using aligned bacterial cellulose (BC) and silver nanowire (AgNW), we fabricated a novel film heater based on Joule heating phenomena. The aligned BC film prepared by stretching BC hydrogel and hot-pressing drying technology showed outstanding mechanical properties and flexibility. The ultrahigh strength of up to 1018 MPa and the toughness of 20 MJ/m3 were obtained for the aligned BC film with 40% wet-stretching (BC-40). In addition, the aligned BC film could be folded into desirable shapes. The AgNW was spray-coated on the surface of aligned BC-40 film and then covered with polydimethylsiloxane to form a P@AgNW@BC heater. P@AgNW@BC heater showed excellent conductivity, which endowed the film heater with an outstanding Joule heating performance. P@AgNW@BC heater could reach ~ 98 â„ƒ at a very low driving voltage of 4 V with a rapid heating response (13 s) and long-term temperature stability. The P@AgNW@BC heater with such an outstanding heating performance can be used as a flexible heating device for different applications in daily life like deicing/defogging device, wearable thermotherapy, etc.Affiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.yes, we confirmed the affiliations are correct. Article title: Kindly check and confirm the edit made in the article title.Thanks, the title is no problem.

The preliminary efficacy of virtual agent-assisted intelligent rehabilitation treatment (Echo app v2.0) in patients with alcohol use disorders: Study protocol for a randomized controlled trial.

Background: Alcohol use disorder (AUD) is one of the most common substance use disorders. People with AUD are in great need of highly accessible and comprehensive management, involving medicine, exercise, and psychotherapy. However, due to limited resources, providing comprehensive treatment for every patient is challenging. Virtual agent-assisted intelligent rehabilitation treatment can improve the accessibility of comprehensive management. Objectives: This randomized controlled trial aims to test whether the virtual agent-assisted intelligent rehabilitation treatment (Echo-app-v2.0) plus treatment as usual (TAU) has greater efficacy than only TAU in AUD. Methods: One hundred participants with AUD will be recruited and randomly assigned to either TAU or virtual agent-assisted intelligent rehabilitation treatment plus TAU based on the 1:1 ratio. The virtual agent-assisted intelligent rehabilitation treatment is delivered by the Echo app v2.0 developed by our research team. Participants will be assessed at baseline, week 4 of treatment, one month, and three months after the end of treatment. The primary outcome is the participants' craving for alcohol, measured by Visual Analogue Scale. Other outcomes include the use of alcohol, motivation for treatment, coping style, depression, anxiety, impulsivity, stress, and sleep quality. Discussion: The virtual agent, with vivid human image, high privacy, and the ability to interact with users, has the potential to play an important role in the delivery of digital psychotherapy. The development of Echo app v2.0 has the possibility to raise the availability of comprehensive treatment for people with AUD.

Develop an efficient and specific AAV-based labeling system for Muller glia in mice.

Reprogramming Müller glia (MG) into functional cells is considered a promising therapeutic strategy to treat ocular diseases and vision loss. However, current AAV-based system for MG-tracing was reported to have high leakage in recent studies. Here, we focused on reducing the leakage of AAV-based labeling systems and found that different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) removed. The leakage ratio of the AAV9-hGFAP-Cre-ΔWPRE decreased by an approximate 40-fold compared with the AAV9-hGFAP-Cre-WPRE labeling system. In addition, we validated the specificity of the AAV-ΔWPRE system for tracing MG reprogramming under Ptbp1-suppression and observed strict non-MG-conversion, similar to previous studies using genetic lineage tracking mouse models. Thus, the AAV9-hGFAP-Cre-ΔWPRE system showed high efficiency and specificity for MG labeling, providing a promising tool for tracing cell fate in vivo.

Internet behavior patterns of adolescents before, during, and after COVID-19 pandemic.

Background: The outbreak of COVID-19 has affected the mental health of adolescents. To describe the Internet behavior-changing patterns of adolescents and to understand the impact of clinical features on changing patterns during the COVID-19 pandemic. Materials and methods: We conducted a cross-sectional cohort study using data collected through online investigation in China. A total of 625 adolescents completed the online survey from May 15 to June 7, 2020. The adolescents were asked to retrospect to the Internet behaviors and game behaviors of three time periods as follows: before the COVID-19 outbreak in China, during the COVID-19 outbreak in China, and back to school. The clinical variables of the demographic data, family functionality, and emotional and behavioral symptoms were also collected. According to the Internet behaviors and game behaviors patterns across the three time periods, the subjects will be sub-grouped. Results: Four Internet behavior-changing patterns during the COVID-19 was identified: (1) Continuous Normal Group (55.52%); (2) Normal to Internet Addiction Group (5.28%); (3) Internet Addiction to Normal Group (14.56%); and (4) Continuous Internet Addiction Group (24.64%). Years of education, academic score ranking, family functionality, and emotional and behavioral symptoms were different across the four groups. Proportions of game behaviors, scores of Strengths and Difficulties Questionnaire (SDQ), and SDQ subscale during the period before the COVID-19 outbreak were significant in predicting changing patterns. Conclusion: The Internet behavior patterns of adolescents during the COVID-19 period were various. Clinical features before the COVID-19 pandemic may predict changing patterns. The heterogeneity in characteristics between different changing patterns should be considered when intervening in adolescents' problematic Internet behavior.

Delivering forestry courses online: experiences, lessons learned, and future of forestry online education in the Asia Pacific.

Innovation in forestry education is needed to address changing contexts of the positionality of forests. This is particularly significant in the Asia-Pacific region, where deforestation and degradation are high. However, the accessibility of high-quality forestry education to address changing regional and global contexts is lacking. A series of innovative sustainable forest management (SFM) open education resource (OER) courses were developed and implemented to improve the accessibility of SFM education to enhance teaching quality, curriculum, and research capacity of universities in the Asia-Pacific Region. To evaluate the SFM-OER program in terms of student experiences, this study investigated student achievement, perceived success of the pedagogical approach and instructional design, and perceived effectiveness of the learning activities in promoting active and transformative learning through the assessment of a 1,191-course feedback survey between 2018 and 2020, including the global pandemic. This study revealed that the program attracted diverse student demographics, including a higher proportion of female students majoring in forestry, ecology, and other environmental studies. Their primary motivation to participate in the courses was to gain international experience, followed by the flexibility of online learning, mandatory course requirements, and earning course credits. Students were satisfied with the Canvas learning management system. Most students spent less than 5 to 10 h of their weekly time in the course and agreed or strongly agreed that the workloads were manageable. Students reflected positively on various learning activities and assignments, such as watching lecture videos, taking quizzes, reading and summarizing, having discussions, and peer review writing. However, they did not clearly prefer specific learning activities, signifying the importance of using diverse learning activities to satisfy diverse individual learning styles in online settings. This analysis contributes to the further development of student-centered pedagogical development for online learning and provides insight into the ways forward for online higher forestry education, while repurposing existing OER courses in a post-Covid-19 era.