Design and Preparation Technology of Green Multiple Solid Waste Cementitious Materials.

For solid waste-based cementitious materials, most scholars focus their research on the hydration reaction of cementitious materials, but there is still a lack of solid waste design that comprehensively considers mechanical properties and durability. Therefore, this article focuses on exploring the mix of design and the microscopic and macroscopic properties of multi solid waste cementitious materials (MSWCMs), namely steel slag (SS), slag powder (SP), desulfurization gypsum (DG), fly ash (FA), and ordinary Portland cement (OPC). According to the orthogonal experimental results, the compressive strength of MSWCMs is optimal when the OPC content is 50% and the SS, SP, DG, and FA contents are 10%, 20%, 5%, and 15%, respectively. The MSWCMs group with an OPC content of 50% and SS, SP, DG, and FA contents of 5%, 15%, 5%, and 25% was selected as the control group. The pure OPC group was used as the blank group, and the optimal MSWCMs ratio group had a 28-day compressive strength of 50.7 megapascals, which was 14% and 7.6% higher than the control group and blank group, respectively. The drying shrinkage rate and resistance to chloride ions were also significantly improved, with maximum increases of 22.9%, 22.6%, and 8.9%, 9.8%, respectively. According to XRD, TG-DTG, and NMR testing, the improvement in macroscopic performance can be attributed to the synergistic effect between various solid wastes. This synergistic effect produces more ettringite (AFt) and C-(A)-S-H gel. This study provides a good theoretical basis for improving the comprehensive performance of MSWCMs and is conducive to reducing the use of cement, with significant economic and environmental benefits.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

An Analysis of Incident Reports Related to Electronic Medication Management: How They Change Over Time.

OBJECTIVE: Electronic medication management (EMM) systems have been shown to introduce new patient safety risks that were not possible, or unlikely to occur, with the use of paper charts. Our aim was to examine the factors that contribute to EMM-related incidents and how these incidents change over time with ongoing EMM use. METHODS: Incidents reported at 3 hospitals between January 1, 2010, and December 31, 2019, were extracted using a keyword search and then screened to identify EMM-related reports. Data contained in EMM-related incident reports were then classified as unsafe acts made by users and the latent conditions contributing to each incident. RESULTS: In our sample, 444 incident reports were determined to be EMM related. Commission errors were the most frequent unsafe act reported by users (n = 298), whereas workarounds were reported in only 13 reports. User latent conditions (n = 207) were described in the highest number of incident reports, followed by conditions related to the organization (n = 200) and EMM design (n = 184). Over time, user unfamiliarity with the system remained a key contributor to reported incidents. Although fewer articles to electronic transfer errors were reported over time, incident reports related to the transfer of information between different computerized systems increased as hospitals adopted more clinical information systems. CONCLUSIONS: Electronic medication management-related incidents continue to occur years after EMM implementation and are driven by design, user, and organizational conditions. Although factors contribute to reported incidents in varying degrees over time, some factors are persistent and highlight the importance of continuously improving the EMM system and its use.

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

Qualitative study of challenges with recruitment of hospitals into a cluster controlled trial of clinical decision support in Australia.

OBJECTIVE: To identify barriers to hospital participation in controlled cluster trials of clinical decision support (CDS) and potential strategies for addressing barriers. DESIGN: Qualitative descriptive design comprising semistructured interviews. SETTING: Five hospitals in New South Wales and one hospital in Queensland, Australia. PARTICIPANTS: Senior hospital staff, including department directors, chief information officers and those working in health informatics teams. RESULTS: 20 senior hospital staff took part. Barriers to hospital-level recruitment primarily related to perceptions of risk associated with not implementing CDS as a control site. Perceived risks included reductions in patient safety, reputational risk and increased likelihood that benefits would not be achieved following electronic medical record (EMR) implementation without CDS alerts in place. Senior staff recommended clear communication of trial information to all relevant stakeholders as a key strategy for boosting hospital-level participation in trials. CONCLUSION: Hospital participation in controlled cluster trials of CDS is hindered by perceptions that adopting an EMR without CDS is risky for both patients and organisations. The improvements in safety expected to follow CDS implementation makes it challenging and counterintuitive for hospitals to implement EMR without incorporating CDS alerts for the purposes of a research trial. To counteract these barriers, clear communication regarding the evidence base and rationale for a controlled trial is needed.

Drug-Drug Interactions and Actual Harm to Hospitalized Patients: A Multicentre Study Examining the Prevalence Pre- and Post-Electronic Medication System Implementation.

INTRODUCTION: Drug-drug interactions (DDIs) have potential to cause patient harm, including lowering therapeutic efficacy. This study aimed to (i) determine the prevalence of potential DDIs (pDDIs); clinically relevant DDIs (cDDIs), that is, DDIs that could lead to patient harm, taking into account a patient's individual clinical profile, drug effects and severity of potential harmful outcome; and subsequent actual harm among hospitalized patients and (ii) examine the impact of transitioning from paper-based medication charts to electronic medication management (eMM) on DDIs and patient harms. METHODS: This was a secondary analysis of the control arm of a controlled pre-post study. Patients were randomly selected from three Australian hospitals. Retrospective chart review was conducted before and after the implementation of an eMM system, without accompanying clinical decision support alerts for DDIs. Harm was assessed by an expert panel. RESULTS: Of 1186 patient admissions, 70.1% (n = 831) experienced a pDDI, 42.6% (n = 505) a cDDI and 0.9% (n = 11) an actual harm in hospital. Of 15,860 pDDIs identified, 27.0% (n = 4285) were classified as cDDIs. The median number of pDDIs and cDDIs per 10 drugs were 6 [interquartile range (IQR) 2-13] and 0 (IQR 0-2), respectively. In cases where a cDDI was identified, both drugs were 44% less likely to be co-administered following eMM (adjusted odds ratio 0.56, 95% confidence interval 0.46-0.73). CONCLUSION: Although most patients experienced a pDDI during their hospital stay, less than one-third of pDDIs were clinically relevant. The low prevalence of harm identified raises questions about the value of incorporating DDI decision support into systems given the potential negative impacts of DDI alerts.

Comparison of the Medium-term Outcomes of Anterior Lumbar Discectomy and Fusion with Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVE: Lumbar degenerative diseases (LDDs) with huge herniation in the left lateral recess or central canal present challenges for oblique lateral lumbar interbody fusion (OLIF) or endoscope-assisted OLIF procedures. Currently, minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the primary approach for this issue. This study aims to provide a standardized technical description of the anterior lumbar discectomy and fusion (ALDF) and evaluate the medium-term clinical effectiveness of both ALDF and MIS-TLIF techniques. METHODS: A retrospective review was performed on LDDs who underwent ALDF and MIS-TLIF surgery from January 2018 to January 2020. The evaluation encompassed various clinical outcomes, such as the visual analogue scale (VAS) scores for back pain and leg pain (VAS-back, VAS-leg), the Oswestry disability index (ODI), the 36-item short-form health survey mental component summary (SF-36 MCS), and the physical component summary (SF-36 PCS). Additionally, radiological parameters, including disc height (DH), segmental disk angle (SDA), lumbar lordosis (LL), and cross-sectional area (CSA), were assessed. Data including radiculopathy, estimated blood loss, operation time, time of getting out of bed, fusion rate, and complications were recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: In total, 47 patients were treated by ALDF and 48 patients were treated by MIS-TLIF. The ALDF group exhibited statistically significant lower estimated blood loss and earlier time of getting out of bed compared to the MIS-TLIF group (p < 0.05). The ALDF group demonstrated lower VAS-back scores and a higher remission rate of low back pain 3 years after the surgery (p < 0.05). During the entire follow-up period, the ALDF group exhibited higher increases in DH and SDA compared to the MIS-TLIF group (p < 0.05). At 6 months, the fusion rate in the ALDF group was significantly higher than in the MIS-TLIF group (p < 0.05). The comparison revealed no statistically significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The ALDF could be considered as a viable surgical alternative for the treatment of LDDs that necessitate ventral neural direct decompression. ALDF exhibited favorable medium-term outcomes in patients with LDDs, displaying advantages in facilitating expedited recovery, enhancing radiographic outcomes, and elevating the remission rate of low back pain. Although ALDF presents slightly higher complication rates compared to MIS-TLIF, it does not adversely affect clinical outcomes.

Effectiveness of fall prevention interventions in residential aged care and community settings: an umbrella review.

INTRODUCTION: Preventing falls is a priority for aged care providers. Research to date has focused on fall prevention strategies in single settings (e.g., residential aged care (RAC) or community settings). However, some aged care providers deliver care, including fall prevention interventions, across RAC and community settings. We conducted an umbrella review to identify what type of fall prevention interventions had the greatest impact on falls outcomes in RAC and community settings. METHODS: Five databases were searched for systematic reviews of falls prevention randomised control trials in older adults living in the community or RAC. Data extracted included systematic review methods, population characteristics, intervention characteristics, setting details (RAC or community), and fall-related outcomes (falls, people who have had a fall, fall-related hospitalisations, and fall-related fractures). Review quality was appraised using the Assessment of Multiple Systematic Reviews-2 tool. RESULTS: One-hundred and six systematic reviews were included; 63 and 19 of these stratified results by community and RAC settings respectively, the remainder looked at both settings. The most common intervention types discussed in reviews included 'exercise' (61%, n = 65), 'multifactorial' (two or more intervention types delivered together) (26%, n = 28), and 'vitamin D' (18%, n = 19). In RAC and community settings, 'exercise' interventions demonstrated the most consistent reduction in falls and people who have had a fall compared to other intervention types. 'Multifactorial' interventions were also beneficial in both settings however demonstrated more consistent reduction in falls and people who fall in RAC settings compared to community settings. 'Vitamin D' interventions may be beneficial in community-dwelling populations but not in RAC settings. It was not possible to stratify fall-related hospitalisation and fall-related fracture outcomes by setting due to limited number of RAC-specific reviews (n = 3 and 0 respectively). CONCLUSION: 'Exercise' interventions may be the most appropriate falls prevention intervention for older adults in RAC and community settings as it is beneficial for multiple fall-related outcomes (falls, fall-related fractures, and people who have had a fall). Augmenting 'exercise' interventions to become 'multifactorial' interventions may also improve the incidence of falls in both settings.

The endosymbiont Serratia symbiotica improves aphid fitness by disrupting the predation strategy of ladybeetle larvae.

Aphids, the important global agricultural pests, harbor abundant resources of symbionts that can improve the host adaptability to environmental conditions, also control the interactions between host aphid and natural enemy, resulting in a significant decrease in efficiency of biological control. The facultative symbiont Serratia symbiotica has a strong symbiotic association with its aphid hosts, a relationship that is known to interfere with host-parasitoid interactions. We hypothesized that Serratia may also influence other trophic interactions by interfering with the physiology and behavior of major predators to provide host aphid defense. To test this hypothesis, we investigated the effects of Serratia on the host aphid Acyrthosiphon pisum and its predator, the ladybeetle Propylaea japonica. First, the prevalence of Serratia in different A. pisum colonies was confirmed by amplicon sequencing. We then showed that harboring Serratia improved host aphid growth and fecundity but reduced longevity. Finally, our research demonstrated that Serratia defends aphids against P. japonica by impeding the predator's development and predation capacity, and modulating its foraging behavior. Our findings reveal that facultative symbiont Serratia improves aphid fitness by disrupting the predation strategy of ladybeetle larvae, offering new insight into the interactions between aphids and their predators, and providing the basis of a new biological control strategy for aphid pests involving the targeting of endosymbionts.

Peroxide derivatives as SARS-CoV-2 entry inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 - trioxolanes (ozonides), with the aim of identifying small molecules that interfere with the RBD-ACE2 interaction. We found that two compounds, compound 21 and 29, exhibit the activity to inhibit RBD-ACE2. They are further demonstrated to inhibit SARS-CoV-2 cell entry, as shown in pseudovirus assay and experiment with authentic SARS-CoV-2. A comprehensive in silico analysis was carried out to study the physicochemical and pharmacokinetic properties, revealing that both compounds have good physicochemical properties as well as good bioavailability. Our results highlight the potential of small molecules targeting RBD inhibitors as potential therapeutic drugs for COVID-19.

Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.

Emergency medicine education via the micro-course and flipped classroom-reform of medical education during the COVID-19 pandemic.

The "micro-course" and "flipped classroom" are emerging tools for medical education but little is known about their utility for emergency medicine teaching. The suitability of the micro-course combined with flipped classroom is investigated for delivery of an emergency medicine course in West Anhui Health Vocational College. Students from Class A and Class B of the Clinical Department of West Anhui Health Vocational College, Grade 2000, were assigned to experimental (micro-course plus flipped classroom, n = 102) and control (traditional, didactic teaching, n = 104) groups, respectively. The effectiveness of teaching was assessed by theoretical tests and questionnaires at the end of the course. Theory test results were significantly better for the experimental group than for controls (t = 3.122, P < .01). General satisfaction of students who had participated in the micro-course plus flipped classroom exceeded that of those who had received traditional teaching. Enthusiasm, efficiency, and learning facility was self-reported to be enhanced by students in the experimental group relative to controls. Use of the micro-course combined with flipped classroom successfully increased the outcome of emergency medicine teaching and may be considered as an approach to reform emergency medicine teaching in medical colleges and universities.

The Application Value of Gemstone Spectral Imaging (GSI) Combined with an 80 mm Wide-body Detector in Head-neck CTA.

OBJECTIVE: This study aims to investigate the value of gemstone spectral imaging (GSI) combined with an 80 mm wide-body detector in head-neck CTA. METHODS: Ninety patients with head-neck CTA were prospectively selected and randomly divided into a control group and a test group, with 45 patients in each group. The control group was scanned conventionally. With a tube voltage of 100 kVp and detector width of 40 mm, a 70 ml contrast agent was injected at a flow rate of 5.0 ml/s. The test group used GSI. With a tube current fixed of 445 mAs and a detector width of 80 mm, the contrast agent was injected at a flow rate of 3.5 ml/s and 0.6 ml/kg body weight, and the 55 keV virtual monoenergetic images (VMIs) were automatically reconstructed. Finally, the target vessel CT values, background noise (BN), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), subjective scores, contrast agent dose, CT dose index volume (CTDIvol), and dose length product (DLP) were recorded. The DLP was converted to the effective dose (ED). RESULTS: The target vessel CT values, BN, SNR, CNR, and subjective scores of the two groups were not statistically significant (all P > 0.05), and the image quality of both groups was the same and met the diagnostic requirements. The contrast agent dose and effective dose (ED) in the test group were approximately 44% and 26% lower than that of the control group, respectively (all P < 0.05). CONCLUSION: In head-neck CTA examination, the Revolution CT GSI combined with an 80 mm wide-body detector can reduce the contrast agent dose and radiation dose while ensuring image quality.

Association between optic atrophy 1 polymorphisms and primary open angle glaucoma risk: Based on a meta-analysis.

BACKGROUND: Emerging evidence suggested a significant association between optic atrophy 1 (OPA1) polymorphisms and primary open angle glaucoma (POAG) risk. However, the current data are inconsistent or even contradictory. Given these, we conducted a meta-analysis to examine the precise association between OPA1 polymorphisms and POAG risk. MATERIALS AND METHODS: Online databases were retrieved, and the related studies were reviewed from inception to December 1, 2022. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of each genetic model. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. RESULT: Overall, 14 studies within 11 publications (involving 2,413 POAG patients and 1,904 controls) were included and some significant association between OPA1 rs166850 C/T (T vs. C: OR = 1.24, 95%CI = 1.06-1.45, P = 0.01, I2 = 39.0%; CT vs. CC: OR = 1.37, 95%CI = 1.05-1.79, P = 0.02, I2 = 41.6%; CT + TT vs. CC: 1.37, 95%CI = 1.06-1.77, P = 0.02, I2 = 41.6%), rs10451941T/C (TC + CC vs. TT: OR = 1.79, 95%CI = 1.41-2.28, P < 0.01, I2 = 71.9%) polymorphisms and POAG susceptibility. In addition, further significant associations were also observed in the stratified analysis, especially in normal tension glaucoma groups and Caucasian descendants. CONCLUSION: The observed evidences suggest that OPA1 polymorphisms may be associate with POAG susceptibility significantly.

Top 100 cited classical articles in sentinel lymph nodes biopsy for breast cancer.

Background: The sentinel lymph node biopsy (SLNB) takes on a critical significance in breast cancer surgery since it is the gold standard for assessing axillary lymph node (ALN) metastasis and determining whether to perform axillary lymph node dissection (ALND). A bibliometric analysis is beneficial to visualize characteristics and hotspots in the field of sentinel lymph nodes (SLNs), and it is conducive to summarizing the important themes in the field to provide more insights into SLNs and facilitate the management of SLNs. Materials and methods: Search terms relating to SLNs were aggregated and searched in the Web of Science core collection database to identify the top 100 most cited articles. Bibliometric tools were employed to identify and analyze publications for annual article volume, authors, countries, institutions, keywords, as well as hotspot topics. Results: The period was from 1998 to 2018. The total number of citations ranged from 160 to 1925. LANCET ONCOLOGY and JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION were the top two journals in which the above articles were published. Giuliano, AE was the author with the highest number of articles in this field with 15. EUROPEAN INST ONCOL is the institution with the highest number of publications, with 35 articles. Hotspots include the following 4 topics, false-negative SLNs after neoadjuvant chemotherapy; prediction of metastatic SLNs; quality of life and postoperative complications; and lymphography of SLNs. Conclusion: This study applies bibliometric tools to analyze the most influential literature, the top 100 cited articles in the field of SLNB, to provide researchers and physicians with research priorities and hotspots.

Machine learning identifies a COVID-19-specific phenotype in university students using a mental health app.

Background: Advances in smartphone technology have allowed people to access mental healthcare via digital apps from wherever and whenever they choose. University students experience a high burden of mental health concerns. Although these apps improve mental health symptoms, user engagement has remained low. Studies have shown that users can be subgrouped based on unique characteristics that just-in-time adaptive interventions (JITAIs) can use to improve engagement. To date, however, no studies have examined the effect of the COVID-19 pandemic on these subgroups. Objective: Here, we sought to examine user subgroup characteristics across three COVID-19-specific timepoints: during lockdown, immediately following lockdown, and three months after lockdown ended. Methods: To do this, we used a two-step machine learning approach combining unsupervised and supervised machine learning. Results: We demonstrate that there are three unique subgroups of university students who access mental health apps. Two of these, with either higher or lower mental well-being, were defined by characteristics that were stable across COVID-19 timepoints. The third, situational well-being, had characteristics that were timepoint-dependent, suggesting that they are highly influenced by traumatic stressors and stressful situations. This subgroup also showed feelings and behaviours consistent with burnout. Conclusions: Overall, our findings clearly suggest that user subgroups are unique: they have different characteristics and therefore likely have different mental healthcare goals. Our findings also highlight the importance of including questions and additional interventions targeting traumatic stress(ors), reason(s) for use, and burnout in JITAI-style mental health apps to improve engagement.

A2AR antagonist treatment for multiple sclerosis: Current progress and future prospects.

Emerging evidence suggests that both selective and non-selective Adenosine A2A receptor (A2AR) antagonists could effectively protect mice from experimental autoimmune encephalomyelitis (EAE), which is the most commonly used animal model for multiple sclerosis (MS) research. Meanwhile, the recent FDA approval of Nourianz® (istradefylline) in 2019 as an add-on treatment to levodopa in Parkinson's disease (PD) with "OFF" episodes, along with its proven clinical safety, has prompted us to explore the potential of A2AR antagonists in treating multiple sclerosis (MS) through clinical trials. However, despite promising findings in experimental autoimmune encephalomyelitis (EAE), the complex and contradictory role of A2AR signaling in EAE pathology has raised concerns about the feasibility of using A2AR antagonists as a therapeutic approach for MS. This review addresses the potential effect of A2AR antagonists on EAE/MS in both the peripheral immune system (PIS) and the central nervous system (CNS). In brief, A2AR antagonists had a moderate effect on the proliferation and inflammatory response, while exhibiting a potent anti-inflammatory effect in the CNS through their impact on microglia, astrocytes, and the endothelial cells/epithelium of the blood-brain barrier. Consequently, A2AR signaling remains an essential immunomodulator in EAE/MS, suggesting that A2AR antagonists hold promise as a drug class for treating MS.

Effects of low-frequency rTMS combined with risperidone on the gut microbiome in hospitalized patients with chronic schizophrenia.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in treating schizophrenia (SCH). However, the effects of the low frequency of rTMS combined with antipsychotics on the gut microbiome in chronic SCH have been poorly investigated. In the present study, psychiatric symptoms were assessed and the stool samples obtained from 33 adult patients with chronic SCH (at baselinephase), 27 after 2 weeks of treatment (rTMS combined with risperidone, SCH-2W), and 37 healthy controls (HC) were analyzed by 16S rRNA gene sequencing. We found that the reduction of phylum Proteobacteria, family Enterobacteriaceae and genera Escherichia-Shigella as well as the increase of genera norank_f_Lachnospiraceae might be related to the antipsychotic effect of rTMS combined with risperidone. These findings indicate that the brain-gut-microbiota axis might be involved in the therapeutic effect of rTMS combined with antipsychotic drugs.

Targeted Knockdown of Genes in the Choroid Plexus.

The choroid plexus (ChP) serves as a critical gateway for immune cell infiltration into the central nervous system (CNS) under both physiological and pathological conditions. Recent research has shown that regulating ChP activity may offer protection against CNS disorders. However, studying the biological function of the ChP without affecting other brain regions is challenging due to its delicate structure. This study presents a novel method for gene knockdown in ChP tissue using adeno-associated viruses (AAVs) or cyclization recombination enzyme (Cre) recombinase protein consisting of TAT sequence (CRE-TAT). The results demonstrate that after injecting AAV or CRE-TAT into the lateral ventricle, the fluorescence was exclusively concentrated in the ChP. Using this approach, the study successfully knocked down the adenosine A2A receptor (A2AR) in the ChP using RNA interference (RNAi) or Cre/locus of X-overP1 (Cre/LoxP) systems, and showed that this knockdown could alleviate the pathology of experimental autoimmune encephalomyelitis (EAE). This technique may have important implications for future research on the ChP's role in CNS disorders.

The investigation of interaction and chaperon-like activity of α-synuclein as a protein in pathophysiology of Parkinson's disease upon direct interaction with tectorigenin.

Analyzing the therapeutic potential of a therapeutic biomolecule requires an understanding of how it may interact with proteins and modify their corresponding functions. α-Synuclein is a protein which is widely involved in the pathogenesis of Parkinson's disease (PD) and shows chaperon-like activity. We have selected tectorigenin, a most common methoxyisoflavone extracted from plants, among therapeutic bioactive molecules that are documented to have different therapeutic effects. Herein, we aimed to explore how tectorigenin interacts with α-synuclein in vitro by mimicking the physiological environment. Spectroscopic as well as theoretical studies including molecular docking simulation, were used to examine the effects of tectorigenin on the conformation and dynamics of α-synuclein. It was shown that tectorigenin is able to quench the protein emission spectra relied on a mixed static-dynamic quenching mechanism. Furthermore, it was displayed that tectorigenin binding to α-synuclein leads to microenvironmental changes in the tertiary structure of protein, however the protein's secondary structure was almost unchanged. It was also deduced that tectorigenin results in thermal stability of α-synuclein structure, evidenced by less perturbation of α-synuclein secondary structure following elevation of temperature in the presence of tectorigenin relative to that of free form. Molecular docking simulation demonstrated that non-covalent reactions, mainly hydrogen bonds, had a key role in the interaction and stabilization of α-synuclein in the presence of tectorigenin. Moreover, chaperon-like activity of α-synuclein was improved in the presence of tectorigenin against two model proteins, ßL-crystallin and catalase. The findings showed that tectorigenin can lead to stabilization of α-synuclein, which may be used as a therapeutic agent in prevention of neurodegenerative diseases.