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Resting-state functional magnetic resonance imaging (fMRI) with graph theoretical modeling has been increasingly applied for assessing whole brain network topological organization, yet its reproducibility remains controversial. In this study, we acquired three repeated resting-state fMRI scans from 16 healthy controls during a strictly controlled in-laboratory study and examined the test-retest reliability of seven global and three nodal brain network metrics using different data processing and modeling strategies. Among the global network metrics, the characteristic path length exhibited the highest reliability, whereas the network small-worldness performed the poorest. Nodal efficiency was the most reliable nodal metric, whereas betweenness centrality showed the lowest reliability. Weighted global network metrics provided better reliability than binary metrics, and reliability from the AAL90 atlas outweighed those from the Power264 parcellation. Although global signal regression had no consistent effects on the reliability of global network metrics, it slightly impaired the reliability of nodal metrics. These findings provide important implications for the future utility of graph theoretical modeling in brain network analyses.

To navigate our complex social world, it is crucial for people to deploy multiple learning strategies, such as learning from directly experiencing the outcomes of one’s actions – experiential learning (EL) – as well as learning from observing the behavior of other people – observational learning (OL). Despite the prevalence of EL and OL in humans and other social animals, two fundamental questions remain unaddressed: how is control over behavior assigned to one strategy over the other depending on the environment? And how do individuals vary in their strategy use? Here, we describe an arbitration mechanism in which the prediction errors associated with each learning strategy influence their weight over behavior. We designed an online behavioral task to test our computational model, in which the uncertainty of each strategy is manipulated, resulting in dynamic variations in prediction errors. Model comparisons revealed that a substantial proportion of participants rely on our proposed arbitration mechanism, but we also found some meaningful heterogeneity in how people solve this task, with four other groups identified: those who use a fixed mixture between the two strategies, those who rely on a single strategy (EL or OL) and non-learners who perform an irrelevant strategy. Furthermore, the groups were found to differ on key behavioral signatures, and on transdiagnostic symptom dimensions relevant to psychopathology, in particular autism traits and anxiety. Together, these results demonstrate the benefits of leveraging large heterogeneous datasets using computational methods to better characterize individual differences and pave the way toward individualized diagnoses and treatment.

Electrochemical oxidation of water and electrolyte ions to produce oxygen, hydrogen peroxide, and peroxysulfate in acid and alkaline electrolytes at the surface of manganese-doped titanium dioxide thin films.

BackgroundThe 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 methodsWe 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.ResultsFour 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.ConclusionThe 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.

In this study, we aimed to examine the prevalence of alcohol consumption among methadone maintenance treatment (MMT) clients in Shanghai and to determine whether a brief intervention (BI) affects drinking among them.A total of 837 clients from 14 local MMT clinics were invited to complete the Alcohol Use Disorders Identification Test (AUDIT). One hundred one were included in the study and randomly assigned to the BI group or the control group. Clients in the BI group received a BI and general health education, whereas clients in the control group received the general health education only. Baseline and postintervention assessments were conducted by using the AUDIT, the Drinking Attitude Questionnaire, the Depression Module of the Patient Health Questionnaire, the Generalized Anxiety Disorder Scale, and the General Well-Being Schedule.Two hundred fifty-nine (30.9%) reported drinking during the last year, and 103 (12.3%) met the criteria for harmful use. At the 3-month follow-up, the AUDIT scores of the 2 groups were significantly decreased, and the time effect was statistically significant (F = 6.224, P = 0.018), but there was no group difference in AUDIT scores (F = 1.953, P = 0.172). Both groups had a main time effect of time on the improvement of depression (F = 8.044, P = 0.008), anxiety (F = 9.650, P = 0.004), and general well-being (F = 5.056, P = 0.033). However, there was no statistical difference between the 2 groups (P0.05), and no statistical difference in the time (F = 1.738, P = 0.198) and group (F = 0.658, P = 0.424) effect of drinking attitude.Alcohol consumption is common among MMT clients in China. Brief intervention, in its current form, could not effectively help them reduce their alcohol consumption.

Introduction PITX3 has been reported to be associated with congenital cataracts, anterior segment mesenchymal dysgenesis, Peters’ anomaly, and microphthalmia. In this case, an infant with unilateral buphthalmos, corneal staphyloma and corneal fistula carrying a variant in PITX3 was reported. Case description We describe a 4-month-old female infant who was referred to our Eye Clinic because of gradual enlargement of the eyeball in the right eye and whitish opacity in both eyes. Buphthalmos with long axial length (22.04 mm), macrocornea with diffuse corneal oedema and opacity (14.50 mm*14.50 mm) and high intraocular pressure (23.78 mmHg) were detected in the right eye. Microphthalmia with short axial length (16.23 mm), microcornea with diffuse corneal oedema and opacity (7.50 mm*6.50 mm) were detected in the left eye. A 360° trabeculotomy was performed for the right eye. However, corneal staphyloma and corneal fistula in the right eye were detected 6 months after the surgery. A variant in exon 4 of PITX3 (c.640_656dup (p. Gly220Profs*95)) was identified in the proband but was not detected in her healthy parents. Conclusion A novel phenotype characterized by unilateral buphthalmos, corneal staphyloma and corneal fistula in an infant were reported to be associated with PITX3 in our study. Our study expands the scope of the clinical heterogeneity of PITX3 variants. It also improves our understanding and increases the attention given to patients with PITX3 variants.

This letter solves a major hurdle that mars photolithography-based fabrication of micro-mesoscale structures in silicon. Conventional photolithography is usually performed on smooth, flat wafer surfaces to lay a 2D design and subsequently etch it to create single-level features. It is, however, unable to process non-flat surfaces (already etched wafers) to create more than one level to give rise to multi-level, 3D, hierarchical structures in the substrate. In this study, we have described a novel cleanroom-based process flow that allows for easy creation of such multi-level, hierarchical structures in a substrate. This is achieved by introducing an ultra-thin sacrificial silicon dioxide hardmask layer on the substrate, which is first 3D patterned via multiple rounds of lithography. Then, this 3D pattern is scaled vertically by a factor of 200 – 300 and transferred to the substrate underneath via a single shot deep etching step. The proposed method is also easily characterizable. Using features of different topographies and dimensions, the etch rates and selectivities were quantified, these characterization information were later used while fabricating specific target structure. Furthermore, this study comprehensively compares the novel pattern transfer technique to already existing methods of creating multi-level structures, like grayscale lithography, chip stacking and double-sided etching. The proposed process was found to be cheaper, faster, and easier to standardize compared to other methods – this makes the overall process more reliable and repeatable. We hope it will encourage more research into hybrid structures that hold the key to dramatic performance improvements in several micro-mesoscale devices.

Chemotherapy is currently the main treatment for unresectable or advanced postoperative gastric cancers. However, its efficacy is negatively affected by the occurrence of chemoresistance, which severely affects patient prognosis. Recently, dysregulation in autophagy has been suggested as a potential mechanism for chemoresistence, and long noncoding RNA (lncRNA) also shows its regulatory role in cancer drug resistance. Using RNA sequencing, we found that lncRNA EIF3J-DT was highly expressed in drug-resistant gastric cancer cells. In-vitro and in-vivo experiments showed that EIF3J-DT activated autophagy and induced drug resistance in gastric cancer cells by targeting ATG14. Bioinformatics and experimental results showed that EIF3J-DT regulated the expression of ATG14 through direct binding to enhance stabilization of ATG14 mRNA and via blocking the degradation of ATG14 mRNA through competitively binding with microRNA (miRNA) MIR188-3p. Therefore, EIF3J-DT increased the expression of ATG14, contributing to activation of autophagy and chemoresistance. Furthermore, it was confirmed that EIF3J-DT and ATG14 were highly expressed in gastric cancer patients resistant to chemotherapy, and this was closely associated with patient prognosis. In conclusion, EIF3J-DT is involved in the regulation of autophagy and chemoresistance in gastric cancer cells by targeting ATG14. It may be a suitable new target for enhancing chemosensitivity and improving prognosis.Abbreviations: 3-MA: 3-methyladenine; 5-Fu: 5-fluorouracil; ATG: autophagy related; C-CASP3: cleaved caspase 3; C-CASP7: cleaved caspase 7; C-PARP: cleaved PARP; CQ: chloroquine; CR: complete response; DIG: digoxigenin; ESR1: estrogen receptor 1; FBS: fetal bovine serum; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; ISH: in situ hybridization; lncRNA: long noncoding RNA; miRNA: microRNA; MUT: mutant; NC: negative control; OXA: oxaliplatin; PBS: phosphate-buffered saline; PD: progressive disease; PFA: paraformaldehyde; PR: partial response; qPCR: quantitative polymerase chain reaction; RAPA: rapamycin; SD: stable disease; TEM: transmission electron microscopy; WT: wild type.

Background Substance use disorder is one of the severe public health problems worldwide. Inequitable resources, discrimination, and physical distances limit patients’ access to medical help. Automated conversational agents have the potential to provide in-home and remote therapy. However, automatic dialogue agents mostly use text and other methods to interact, which affects the interaction experience, treatment immersion, and clinical efficacy. Objective The aim of this paper is to describe the design and development of Echo-APP, a tablet-based app with the function of a virtual digital psychotherapist, and to conduct a pilot study to explore the feasibility and preliminary efficacy results of Echo-APP for patients with methamphetamine use disorder. Methods Echo-APP is an assessment and rehabilitation program developed for substance use disorder (SUD) by a team of clinicians, psychotherapists, and computer experts. The program is available for Android tablets. In terms of assessment, the focus is on the core characteristics of SUD, such as mood, impulsivity, treatment motivation, and craving level. In terms of treatment, Echo-APP provides 10 treatment units, involving awareness of addiction, motivation enhancement, emotion regulation, meditation, etc. A total of 47 patients with methamphetamine dependence were eventually enrolled in the pilot study to receive a single session of the Echo-APP–based motivational enhancement treatment. The outcomes were assessed before and after the patients’ treatment, including treatment motivation, craving levels, self-perception on the importance of drug abstinence, and their confidence in stopping the drug use. Results In the pilot study, scores on the Stages of Change Readiness and Treatment Eagerness Scale and the questionnaire on motivation for abstaining from drugs significantly increased after the Echo-APP–based treatment (P Conclusions Echo-APP is a practical, accepted, and promising virtual digital psychotherapist program for patients with methamphetamine dependence. The preliminary findings lay a good foundation for further optimization of the program and the promotion of large-scale randomized controlled clinical studies for SUD.

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.

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca2+ transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.

Phase change thermal management devices including heat pipes and ultra-thin vapor chambers can remove and spread the excess heat from microprocessors more efficiently compared with the conventional heat sinks. However, the capillary and CHF limits of the evaporator section remained a challenge for high heat flux (> 100 Wcm−2) large area (> 5 × 5 mm2) applications. In this study, a hybrid microporous structure consists of copper wire meshes (CWMs) as the liquid delivery routing and copper inverse opals (CIOs) film as the boiling/evaporation platform is proposed. The feasibility of the approach and the design optimization were studied with extensive modeling and CFD simulations. For the experiment setup, the heater and the RTD sensors are fabricated over a Silicon chip using the conventional micro fabrication processes and the micro porous copper film is deposited based on template-assisted electrodeposition, resulting in CIOs structure with average 5 μm pore size, 1 μm neck, and 15 μm thickness. A copper wire mesh structure (500 μm thickness, 0.5 porosity, 71 μm wire diameter) with 4 × 4 tile openings (1 × 1 mm2 area per tile) was fixed over the CIOs film with mechanical constraints. A flow loop and vapor chamber are designed and fabricated to perform capillary boiling experiments in a saturated environment (liquid water and vapor at ∼100°C). The hybrid microporous structure was able to remove over 75 W from the 5 × 5 mm2 heater area (over 300 W cm−2 heat flux) with 9°C super heat resulting in thermal resistance of 0.03 cm2°CW−1 at the CHF. The findings of this study are largely beneficial for the design and fabrication of high performance evaporator wicks and next-generation heat routing technologies.

Two-phase, capillary-fed cooling devices are appealing thermal management technologies due to their potential for high heat transfer performance and ease of system-level integration. While existing evaporative wicking structures such as copper inverse opals (CIOs) and copper wire meshes (CWMs) have shown promise for achieving target heat dissipation rates of 100 Wcm−2 or greater, the reliability of these structures for long-term device operation and optimal capillary-driven boiling performance has not received much attention. To ensure proper functionality of the evaporator wick, the microporous copper structures must retain a hydrophilic contact angle during device operation. Surface oxidation of the copper is a critical degradation mechanism that must be addressed to preserve the integrity of the wick. In this study, we systematically investigate the contact angle change of untreated copper and various copper oxides under different conditions. To avoid the formation of hydrophobic Cu2O, we pre-oxidize the copper micro porous wick to form hydrophilic cupric oxide CuO and study the effect of various thermal and chemical oxidation recipes on the hydrophilicity and morphology of the resulting structures. A chemical oxidation formula is implemented for the creation of a stable superhydrophilic surface at a low temperature (70°C) for copper inverse opals (CIOs) (5 μm pore size) and copper wire meshes (CWMs) (76 μm pore opening). The recipe has been optimized to create nano CuO needles with a length of < 100 nm and keep the necks (∼1 μm diameter) open for better capillary wicking of the working fluid. The findings of this study potentially benefit the development of copper-based capillary-fed cooling devices.

Organic films were widely found on indoor impermeable surfaces exposed to gaseous organic compounds, but few studies have addressed the film growth details on different indoor substrates. In this study, we observed the topography evolution of phthalic acid ester (PAE) organic films on three impermeable substrates: polished glass (G-P), mirror-polished stainless steel (SS-M) and drawn stainless steel (SS-D). PAE organic films were preferentially formed upon the flat surface with sparse inherent nano-peaks of substrate G-P and in valleys of substrate SS-M and SS-D. Surface uniformity of substrates and viscosity of PAE molecules were inferred as critical parameters determining the surface average adhesion forces. We obtained the partition coefficients of DEP, DnBP, BBP and DEHP on substrate G-P, SS-M and SS-D by fitting the initial monolayer adsorption process. Organic films continuously grew instead of reaching adsorption equilibrium after long-term PAE exposure, indicating that multilayer adsorption may occur. The organic film growth rates in saturated gas-phase PAE concentrations were quantified as about one-tenth of the results in previous studies where substrates were simultaneously exposed to multiple pollutants. To sum up, the results outline PAE adsorption details on impermeable materials and provide a reference for better estimation on PAE exposure assessment.

BackgroundPrevious studies have identified the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on cravings of patients with methamphetamine use disorder (MUD). However, the mechanism underlying the treatment effect remains largely unknown. A potential candidate mechanism could be that rTMS over the dorsolateral prefrontal cortex (DLPFC) modulates the attention bias to methamphetamine-related cues. The purpose of this study is therefore to determine the modulation of rTMS on methamphetamine-related attention bias and the corresponding electrophysiological changes.MethodsForty-nine patients with severe MUD were included for analysis. The subjects were randomized to receive the active intermittent theta-burst stimulation (iTBS) or sham iTBS targeting DLPFC for 20 sessions. Participants performed the Addiction Stroop Task before and after the treatment while being recorded by a 64-channel electroencephalogram. Baseline characteristics were collected through the Addiction Severity Index.ResultsPost-treatment evaluations showed a reduced error rate in discriminating the color of methamphetamine words in the active iTBS group compared with the sham iTBS group. Following rTMS treatment, we found the significant time-by-group effect for the N1 amplitude (methamphetamine words > neutral words) and P3 latency (methamphetamine words > neutral words). The change of N1 amplitude was positively correlated with cravings in the active group. Moreover, reduced power of neural oscillation in the beta band, manifesting at frontal central areas, was also found in the active group.ConclusionThis study suggests that attention bias and the beta oscillation during the attentional processing of methamphetamine words in patients with MUD could be modulated by iTBS applied to left DLPFC.

Capillary-fed boiling in microporous copper inverse opals (CIOs) is capable of removing an excess of 1 kW/cm2 at 10–15 °C superheat over small wicking distances ∼ 200 μm. In order to remove heat from large area chips (> 1 cm2), longer capillary wicking distance is desired to reduce the manufacturing complexity of the 3D manifold for liquid delivery and vapor extraction. In this study, we propose graded copper inverse opals (g-CIOs) where smaller pores at the bottom provide high capillary pressure for liquid delivery, while larger pores at the top reduce viscous pressure drop for vapor extraction. This nonhomogeneous wicking material decouples the permeability and capillary pressure in the vertical and lateral directions, resulting in greater CHFs and capillary wicking distances. In this study, we demonstrate the feasibility of fabricating g-CIOs material with up to three different pore diameters (2 μm, 5 μm, and 10 μm) using a multi-step template sintering and copper electrodeposition process. We then leverage and expand upon a well-calibrated experimental model for the prediction of CHF in monoporous CIOs to map the performance metrics for g-CIOs. The model combines a hydraulic resistance network with Darcy’s law and accounts for the nonhomogeneous permeabilities in lateral and vertical directions. Using this model, we study the impact of total wick thickness and graded pore-size combinations on the critical heat fluxes and wicking distances. Our modeling results conclude that a two-layer g-CIOs can potentially reach ∼70% enhancement in the critical heat flux or ∼30% enhancement in the wicking length compared to monoporous CIOs of the same thickness. Our fabrication capability and preliminary modeling results offer the opportunity to design boiling tests with optimized g-CIOs and exploring the potential of dissipating high heat flux for large area cooling applications.

Transforming growth factor β (TGF-β) drives epithelial-mesenchymal transition (EMT), playing vital roles in cancer metastasis. The crosstalk between microRNAs (miRNAs) and TGF-β are frequently observed and involved in TGF-β-induced EMT. Here, we determine that miR-577 is significantly upregulated in gastric cancer (GC). miR-577 expression is positively correlated with GC metastasis status and poor patient prognosis. Functional assays demonstrate that miR-577 promotes metastasis and chemoresistance by inducing EMT and stemness-like properties. Moreover, TGF-β promotes the expression of miR-577, and miR-577 participates TGF-β-mediated cancer metastasis. Mechanistically, TGF-β activates miR-577 via NF-κB-mediated transcription, and miR-577 enhances TGF-β signaling by targeting the serum deprivation protein response (SDPR), which directly interacts with ERK to inactivate the ERK-NF-κB pathway, hence forming a feedback loop to drive tumor metastasis. A plausible mechanism of EMT induction by the TGF-β network is elucidated. Our findings suggest that the TGF-β-miR-577-SDPR axis may be a potential prognostic marker and therapeutic target against cancer metastasis in GC., Luo et al. find that mir-577 can be as a prognostic marker and therapeutic target against cancer metastasis in gastric cancer. TGF-β activates miR-577 via NF-κB-mediated transcription, and miR-577 enhances TGF-β signaling by forming a feedback loop with SDPR-ERK-NF-κB pathway.

BackgroundTemporal interference (TI) stimulation is a new technique of noninvasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidate.ObjectiveTo assess the effectiveness and safety aspect of the envelope-modulated waveform of TI stimulation on human primary motor cortex (M1).MethodsParticipants attended three sessions of 30-min TI stimulation at 2 mA during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.ResultsIn the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.ConclusionThese results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and pave the way for further explorations.

Chemotherapy is currently the main treatment for unresectable or advanced postoperative gastric cancers. However, its efficacy is negatively affected by the occurrence of chemoresistance, which severely affects patient prognosis. Recently, dysregulation in autophagy has been suggested as a potential mechanism for chemoresistence, and long noncoding RNA (lncRNA) also shows its regulatory role in cancer drug resistance. Using RNA sequencing, we found that lncRNA EIF3J-DT was highly expressed in drug-resistant gastric cancer cells. In-vitro and in-vivo experiments showed that EIF3J-DT activated autophagy and induced drug resistance in gastric cancer cells by targeting ATG14. Bioinformatics and experimental results showed that EIF3J-DT regulated the expression of ATG14 through direct binding to enhance stabilization of ATG14 mRNA and via blocking the degradation of ATG14 mRNA through competitively binding with microRNA (miRNA) MIR188-3p. Therefore, EIF3J-DT increased the expression of ATG14, contributing to activation of autophagy and chemoresistance. Furthermore, it was confirmed that EIF3J-DT and ATG14 were highly expressed in gastric cancer patients resistant to chemotherapy, and this was closely associated with patient prognosis. In conclusion, EIF3J-DT is involved in the regulation of autophagy and chemoresistance in gastric cancer cells by targeting ATG14. It may be a suitable new target for enhancing chemosensitivity and improving prognosis. Abbreviations: 3-MA: 3-methyladenine; 5-Fu: 5-fluorouracil; ATG: autophagy related; C-CASP3: cleaved caspase 3; C-CASP7: cleaved caspase 7; C-PARP: cleaved PARP; CQ: chloroquine; CR: complete response; DIG: digoxigenin; ESR1: estrogen receptor 1; FBS: fetal bovine serum; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; ISH: in situ hybridization; lncRNA: long noncoding RNA; miRNA: microRNA; MUT: mutant; NC: negative control; OXA: oxaliplatin; PBS: phosphate-buffered saline; PD: progressive disease; PFA: paraformaldehyde; PR: partial response; qPCR: quantitative polymerase chain reaction; RAPA: rapamycin; SD: stable disease; TEM: transmission electron microscopy; WT: wild type.

Background During the coronavirus disease 2019 (COVID-19) pandemic, Fangcang shelter hospitals were opened in Wuhan, China, to isolate and care for patients with mild or moderate symptoms. The patients and staff in the hospitals faced mental health challenges. This paper reports the experiences and mental health needs from them. Method Following the qualitative design, semi-structured interviews were conducted in the EastWest Lake Fangcang Shelter Hospital, Wuhan on March 2020. Data collection and analysis was based on grounded theory. Open coding was adapted and a structured codebook was developed through coding seminars. The themes and subthemes were then confirmed through thematic analysis. The findings were further explained and integrated in a theoretical framework. Results A total of 10 COVID-19 patients and 13 staff, including doctors, nurses, psychiatrists, and policemen participated in the interviews. They have common needs, as well as their own needs. The perspectives from the staff also did complement for needs of the patients. The mental health needs were generalized into four themes, that is, basic needs, information and communication, emotional needs, and social support, each with several subthemes. In addition, there were some external factors that regulated the internal needs, which were summarized in a theoretical framework. Conclusions The study indicates the directions on hospital management, mental health services, policy making, and social work to meet the mental health needs of the inpatients and staff from temporary shelter hospitals like Fangcang in Wuhan during the COVID-19 pandemic.

Background: The diagnostic guideline of Gaming Disorder was a new category proposed in the draft of ICD-11 by WHO’s Department of Mental Health and Substance Abuse (MSD) in 2018 and its reliability and clinical utility based on Chinese population has not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and culture applicability of diagnostic guidelines of gaming disorder in ICD-11, and its comparability to the diagnostic guideline in DSM-5 in China. Methods: Participants included 21 pair clinical raters which constituted of seven psychiatrists and 200 gaming players aged from 15-18 years old with different risk level of Internet addiction based on the scores of Young’s Internet Addiction Test. Each participant received a semi-structured face-to-face interview by a paired clinical raters at the same time. Then clinical raters made the diagnoses and filled the clinical utility questionnaire independently within 30 minutes after the interview through an electronic platform according to the diagnostic guidelines for gaming disorder in both ICD-11 and DSM-5. In addition, two focus groups were conducted to inform the applicability, feasibility and preference of diagnostic guidelines for gaming disorder in ICD-11 in China. Outcomes: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0∙545( p

Objectives The purpose of the study was to investigate whether Group Music Therapy (GMT) could enhance the treatment motivation and change the negative emotion among female patients with methamphetamine use disorder in a randomized clinical trial. Methods Participants ( N = 60) were randomized to the group of GMT combined with treatment as usual (TAU) or the group with TAU only. Questionnaire of Motivation for Abstaining from Drugs was used to measure the motivation for abstaining from drugs of the female patients. And Self-Rating Depression Scale and Self-Rating Anxiety Scale were used to measure negative emotion of participants. The measurements were conducted at T0 (baseline), T1 (post 13 sessions of intervention) and T2 (3-month follow-up after T1) by the independent trained researcher. Results The postintervention and 3-month follow-up results according to the intention-to-treat principle indicated that GMT + TAU intervention showed significantly positive group-by-time effect on the scores of the subscale-tending to rehabilitation-internal motivation ( p = 0.01) and avoiding abuse-external motivation ( p = 0.04). In 3-month follow-up, total scores of the questionnaire of motivation for abstaining from drugs ( p = 0.02), scores of avoiding abuse-internal motivation subscale ( p = 0.05), and scores of confidence of abstaining from drugs subscale ( p = 0.01) in GMT + TAU were also presented with significantly positive group x time effect. The changes of total score of Questionnaire of Motivation for Abstaining from Drugs (from baseline to 3-month follow-up) was significantly positive association with the changes of scores of SAS in GMT + TAU group ( r = −0.55, p = 0.00). Conclusions The present study suggests that GMT could be used as an effective treatment strategy to enhance treatment motivation of female patients with methamphetamine use disorder.

Summary Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020)., Graphical abstract, Highlights • Protocol for applying repetitive TMS to decrease the craving and relapse • Accurate positioning is one of the crucial steps of repetitive TMS treatment • The treatment process requires continuous attention to the patient’s response, Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics.

Although previous studies have reported correlations between alpha oscillations and the “retention” sub-process of working memory (WM), no direct causal evidence has been established in human neuroscience. Here, we developed an online phase-locking closed-loop transcranial alternating current stimulation (tACS) system capable of precisely controlling the phase difference between tACS and concurrent endogenous oscillations. This system permits both up- and down-regulation of brain oscillations at the target stimulation frequency, and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to 39 participants during the retention intervals of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. Moreover, the in-phase tACS-induced changes in WM performance were positively correlated with alpha oscillatory activity. These findings strongly support a causal link between alpha oscillations and WM retention, and illustrate the broad application prospects of phase-locking tACS.

We investigated the effect of curcumin on liver anti-oxidative stress in the type 1 diabetic rat model induced by streptozotocin (STZ). Experimental diabetic rats were induced by STZ intraperitoneally. All rats were fed for 21 days including three groups of control (NC), diabetic model (DC) and curcumin-treated (Cur, 1.5 g/kg by gavage). The results showed that curcumin-treatment significantly decreased the blood glucose and plasma malondialdehyde levels, but significantly increased the plasma superoxide dismutase, glutathione peroxidase and reduced glutathione levels. Curcumin treatment decreased the activity of aldose reductase, but increased the plasma glucose-6-phosphate dehydrogenase, glucose synthetase and glucose-polymerizing activities. Curcumin treatment significantly decreased the protein of protein kinase C (PKC) and poly ADP ribose polymerase (PARP) expression in the Cur group compared with the DC group. Moreover, the sorbitol dehydrogenase activity was significantly decreased and deterred glucose enters into the polyol pathway leading to an increased NADPH content in the Cur group compared with the DC group. Our data provides evidence that oxidative stress in diabetic rats may be attenuated by curcumin by inhibiting polyol pathway associated with down-regulated expression of PKC and PARP, as evidenced by both an increase the antioxidant enzymes levels and glycogen biosynthesis enzymes activities.

Animal studies have reported the brain glutamatergic dysfunction in substance dependence. However, proton magnetic resonance spectroscopy (1H-MRS) studies of glutamate in substance-dependent patients published contradicting results. In order to investigate the characteristics of brain glutamatergic alterations in substance-dependent patients, we conducted systematic reviews and meta-analyses of 1H-MRS studies that have investigated the glutamate, glutamine, and Glx (glutamate + glutamine) concentration in substance-dependent patients. Multiple databases were searched until Sep 10, 2020. Twenty-nine studies comprising 982 patients and 787 controls were included. There was significantly decreased glutamate level in dorsolateral prefrontal cortex in patients compared with controls. Higher glutamate levels in medial prefrontal cortex and basal ganglia region were also demonstrated in patients compared with controls. Subgroup analyses based on the substance type and abstinence period (short vs medium-term abstinence period) were performed. The results revealed Glx and glutamate concentrations in all investigated brain regions were not different in patients with any types of substance dependence compared with controls. The abstinence period had no effect on the glutamate levels. In summary, substance dependence is associated with glutamatergic dysfunction of prefrontal cortex and basal ganglia. Present findings partially support the hypothesis that addiction is associated with abnormal brain glutamatergic neurotransmission.

Inflammation is closely related to the pathogenesis and prognosis of cardiovascular disease (CVD). Interleukin-37 (IL-37), an anti-inflammatory IL-1 family cytokine, shifts cytokine expression from pro- to anti-inflammation via regulation of macrophage polarization and lipid metabolism. In macrophages, IL-37 functions through both intracellular and extracellular pathways to regulate the activity of NF-kB and PTEN as well as the expression of cytokines, including IL-1β, IL-6, and IL-10. Moreover, IL-37 levels are increased in the serum of patients with heart failure, atherosclerosis, and acute coronary syndrome with no evidence of anti-inflammatory effects. However, transgenic overexpression of IL-37 improves cardiac infarct and attenuates atherosclerosis plaque expansion. Hence, it is worthwhile to investigate the precise mechanism and role of IL-37 in the pathogenesis of CVD, which may provide deeper understanding of the inflammatory response in this context. This review summarizes the regulatory role of IL-37 in systematic inflammation induced by CVD and highlights recent advancements in the clinical application of IL-37 as a therapeutic agent or biomarker for diagnosis of CVD.

Background: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. Methods: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). Findings: The three real TBS groups had more craving decrease effect than the sham group (p

The aim of the present study was to determine the effects of curcumin on antioxidants using a rat model of type 1 diabetes. Seven‑week‑old male Sprague‑Dawley rats were injected with Streptozotocin (STZ) intraperitoneally to induce this model, and then treated with 1.0% curcumin (weight ratio) mixed in their diet for 21 days. The present study included three groups: Control group (NC), diabetic rat model group (DC) and a curcumin treated group (Diab‑Cur). The results demonstrated that curcumin treatment markedly decreased the blood glucose levels, plasma malondialdehyde concentration and plasma activity of glutathione peroxidase (GSH‑Px) and catalase (CAT); however, it increased the plasma superoxide dismutase (SOD) and insulin levels. Curcumin treatment increased the expression of the CAT, GSH‑Px, HO‑1 and norvegicus NAD(P)H quinone dehydrogenase 1, and decreased the SOD1 expression, which, led to a diminished oxidative stress status. In addition, curcumin treatment significantly increased the protein expression of Keap1 in the Diab‑Cur group when compared with the DC group, decreased cytosolic concentrations of Nrf2 while increasing nuclear accumulation of Nrf2. The results provide evidence that oxidative stress in the STZ‑induced diabetic rat model may be attenuated by curcumin via the activation of the Keap1‑Nrf2‑ARE signaling pathway, as evidenced by a decrease in the blood glucose concentration and an increase in the transcription of several antioxidant genes.

Background Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated with the colon cancer 1 (MACC1) predicted poor prognosis of GC and promoted tumor cells proliferation and invasion. In this study, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 reversed this resistance. Methods The effect of trastuzumab and glycolysis inhibitor combination on cell viability, apoptosis, and cell metabolism was investigated in vitro using established trastuzumab-resistant GC cell lines. We assessed the impact of trastuzumab combined with oxamate on tumor growth and metabolism in an established xenograft model of HER2-positive GC cell lines. Results Here, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 in trastuzumab-resistant cells reversed this resistance. Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects. Moreover, when the PI3K/AKT signaling pathway was inhibited, the effects of MACC1 on resistance and glycolysis were diminished. Our findings indicated that MACC1 promoted the Warburg effect mainly through the PI3K/AKT signaling pathway, which further enhanced GC cells trastuzumab resistance. Conclusions Our results indicate that co-targeting of HER2 and the Warburg effect reversed trastuzumab resistance in vitro and in vivo, suggesting that the combination might overcome trastuzumab resistance in MACC1-overexpressed, HER2-positive GC patients. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0302-1) contains supplementary material, which is available to authorized users.

Tables S1 to S4. Table S1: IC50 of different GC cell lines. Table S2: IC50 and RI (resistance index) of MKN45 cells after treatment with trastuzumab at different inducing concentrations. Table S3: Fa and CI for trastuzumab and glucolysis inhibitor combinations on inhibition of cell viability. Table S4: Fa and CI for trastuzumab and glucolysis inhibitor combinations on inhibition of glucose uptake. (DOCX 45Â kb)

The education contents of different engineering majors have varied greatly, and each specific major has its own discretion of professional curriculum establishment. How to objectively probe the advances of majors and make right use of this decision-making power is an essential link in the comprehensive education reform of engineering majors. The shifts of professional education focus in engineering majors were obtained by analyzing related bibliometrics. First a hierarchical classification of professional literature related to a specific major is formed, and the literature number of each group in the hierarchical classification is recorded in a chronological sequence, then the relationship between the literature number and time is established by mathematical regressions, subsequently the drifting pattern of key knowledge points within the major being deduced in the form of quantitative models, which enable us to objectively discover shifts of education focus in the engineering major and sensibly facilitate arranging curriculums and amending/compiling textbooks, modulating teaching and experiments. This method was applied in the mineral processing

The snake-like robot needs to adapt to complex environment, in order to reach the target point safely and collisionless, necessary obstacle avoidance strategy is of vital importance. In this paper, laser radar and ultrasonic sensors are used to detect the surrounding environment, and then information fusion method based on TS fuzzy neural network is adopted to integrate the collected information, which provides the necessary condition for obstacle avoidance research of the snake-like robot. Experiments show that the snake-like robot can successfully avoid obstacles to reach the target point after training of the fuzzy neural network.