Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

Brassinosteroids biosynthetic gene MdBR6OX2 regulates salt stress tolerance in both apple and Arabidopsis.

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Translation, cross-cultural adaptation, reliability, and validity of the Chinese version of the intensive care unit environment stress scale for pediatric patients.

PURPOSE: There is currently a lack of understanding of children's experience in the pediatric intensive care unit (PICU) environment. Additionally, pediatric patients may experience post-PICU syndrome following discharge. Thus, we aimed to adapt and evaluate the psychometric properties of a tool specifically for use with children in the PICU. DESIGN AND METHODS: According to Brislin's Model, the Intensive Care Unit Environment Stress Scale (ICUESS) was translated both forward and backward and adapted cross-culturally. A total of 210 PICU patients were selected from four hospitals in XXX to analyze the final translated version of the questionnaire, the Pediatric Intensive Care Unit Environmental Stress Scale (PICUESS). Content validity, exploratory factor analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to assess the validity, while reliability was assessed using Cronbach's alpha and split-half reliability analysis. RESULTS: For PICUESS, seven of 42 items were modified. Content validity was high (overall = 0.96, item validity = 0.8 to 1.0). Exploratory factor analysis revealed eight common factors (Kaiser-Meyer-Olkin = 0.857, significant Bartlett's test). The results of the CFA indicate that the scale model fits well across the 8 factors. The entire scale demonstrated excellent internal consistency (Cronbach's alpha = 0.934). The overall split-half reliability was 0.935. CONCLUSIONS: The Chinese version of PICUESS demonstrates good reliability and validity, making it suitable for assessing pediatric patients' perceptions of the PICU environment. PRACTICE IMPLICATIONS: The PICUESS can assist healthcare professionals in providing personalized environment care for PICU patients. It has the potential to serve as a tool for further testing and international comparisons of pediatric patients' perceptions of the PICU environment.

Perceptions and self-management of a healthy diet among middle-aged adults with risk of stroke in North China: a qualitative exploration.

OBJECTIVE: Although stroke is prevalent among older people, there is a rising incidence among the younger subpopulations, particularly middle-aged adults. A healthy diet is one of the key modifiable factors to primary prevention of stroke among these subpopulations, yet there is limited understanding of the dietary habits among middle agers who have the risk factor(s) but no occurrence of stroke. This study aims to explore the views on perceptions and the self-management of middle-aged adults at risk of stroke on a healthy diet and to identify the enablers and barriers that could inform the future development of dietary interventions. DESIGN: This study used an interpretive descriptive qualitative design, employing semistructured purposive sampling for focus group discussions. Thematic analysis was conducted on the transcribed interviews and field notes, facilitated by NVivo 12.0 Plus software. SETTING: Community settings in Zhengzhou City, Henan Province. PARTICIPANTS: Middle-aged adults (aged 45-59) were identified as at risk of stroke due to the presence of one or more modifiable risk factors. RESULT: A total of seven focus group discussions were audio recorded. Four main themes emerged, which were: (1) cognitive understanding of a healthy diet; (2) dietary practices; (3) knowledge acquisition and (4) barriers to dietary adherence. CONCLUSIONS: The middle-aged adults at risk of stroke were generally aware of the risk and attempted to practise healthy eating. The existing educational programmes on following a healthy diet in the prevention of disease need to be made more comprehensible, accessible and equitable, especially for those from socioeconomically disadvantaged communities.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Efficient Fabrication of Quartz Glass Using Laser Coaxial Powder-Fed Additive Manufacturing Approach.

This article investigates a laser-directed energy deposition additive manufacturing (AM) method, based on coaxial powder feeding, for preparing quartz glass. Through synergistic optimization of line deposition and plane deposition experiments, key parameters of laser coaxial powder feeding AM were identified. The corresponding mechanical properties, thermal properties, and microstructure of the bulk parts were analyzed. The maximum mechanical strength of the obtained quartz glass element reached 72.36 ± 5.98 MPa, which is ca. 95% that of quartz glass prepared by traditional methods. The thermal properties of the obtained quartz glass element were also close to those prepared by traditional methods. The present research indicates that one can use laser AM technology that is based on coaxial powder feeding to form quartz glass with high density and good thermodynamic properties. Such quartz glass has substantial potential in, for example, optics and biomedicine.

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages.

Echinatin is an active ingredient in licorice, a traditional Chinese medicine used in the treatment of inflammatory disorders. However, the protective effect and underlying mechanism of echinatin against acute lung injury (ALI) is still unclear. Herein, we aimed to explore echinatin-mediated anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated ALI and its molecular mechanisms in macrophages. In vitro, echinatin markedly decreased the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated murine MH-S alveolar macrophages and RAW264.7 macrophages by suppressing inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression. Furthermore, echinatin reduced LPS-induced mRNA expression and release of interleukin-1ß (IL-1ß) and IL-6 in RAW264.7 cells. Western blotting and CETSA showed that echinatin repressed LPS-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways through targeting transforming growth factor-beta-activated kinase 1 (TAK1). Furthermore, echinatin directly interacted with Kelch-like ECH-associated protein 1 (Keap1) and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to enhance heme oxygenase-1 (HO-1) expression. In vivo, echinatin ameliorated LPS-induced lung inflammatory injury, and reduced production of IL-1ß and IL-6. These findings demonstrated that echinatin exerted anti-inflammatory effects in vitro and in vivo, via blocking the TAK1-MAPK/NF-κB pathway and activating the Keap1-Nrf2-HO-1 pathway.

Mental health problems of front-line medical staff in the early stage of public health emergencies.

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention.

FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

Boosting thermal energy transport across the interface between phase change materials and metals via self-assembled monolayers.

Thermal energy storage using phase change materials (PCMs) has great potential to reduce the weather dependency of sustainable energy sources. However, the low thermal conductivity of most PCMs is a long-standing bottleneck for large-scale practical applications. In modifications to increase the thermal conductivity of PCMs, the interfacial thermal resistance (ITR) between PCMs and discrete additives or porous networks reduces the effective thermal energy transport. In this work, we investigated the ITR between a metal (gold) and a polyol solid-liquid PCM (erythritol) at various temperatures including temperatures below the melting point (300 and 350 K), near the melting point (390, 400, 410 K, etc) and above the melting point (450 and 500 K) adopting non-equilibrium molecular dynamics. Since the gold-erythritol interfacial thermal conductance (ITC) is low regardless of whether erythritol is melted or not (<40 MW m-2K-1), self-assembled monolayers (SAMs) were used to boost the interfacial thermal energy transport. The SAM with carboxyl groups was found to increase the ITC most (by a factor of 7-9). As the temperature increases, the ITC significantly increases (by ∼50 MW m-2K-1) below the melting point but decreases little above the melting point. Further analysis revealed that the most obvious influencing factor is the interfacial binding energy. This work could build on existing composite PCM solutions to further improve heat transfer efficiency of energy storage applications in both liquid and solid states.

Construction of a grpE-based plasmid addiction system in Escherichia coli and its application in phloroglucinol biosynthesis.

AIM: Biotechnical processes in Escherichia coli often operate with artificial plasmids. However, these bioprocesses frequently encounter plasmid loss. To ensure stable expression of heterologous genes in E. coli BL21(DE3), a novel plasmid addiction system (PAS) was developed. METHODS AND RESULTS: This PAS employed an essential gene grpE encoding a cochaperone in the DnaK-DnaJ-GrpE chaperone system as the selection marker, which represented a chromosomal ΔgrpE mutant harboring episomal expression plasmids that carry supplementary grpE alleles to restore the deficiency. To demonstrate the feasibility of this system, it was implemented in phloroglucinol (PG) biosynthesis, manifesting improved host tolerance to PG and increased PG production. Specifically, PG titer significantly improved from 0.78 ± 0.02 to 1.34 ± 0.04 g l-1, representing a 71.8% increase in shake-flask fermentation. In fed-batch fermentation, the titer increased from 3.71 ± 0.11 to 4.54 ± 0.10 g l-1, showing a 22.4% increase. RNA sequencing and transcriptome analysis revealed that the improvements were attributed to grpE overexpression and upregulation of various protective chaperones and the biotin acetyl-CoA carboxylase ligase coding gene birA. CONCLUSION: This novel PAS could be regarded as a typical example of nonanabolite- and nonmetabolite-related PAS. It effectively promoted plasmid maintenance in the host, improved tolerance to PG, and increased the titer of this compound.

Meta-Analysis of Efficacy of Platelet-Rich Plasma Combined with Minoxidil for Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous. OBJECTIVE: To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA). METHODS: We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment. RESULTS: A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone. CONCLUSIONS: This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Causal association between systemic lupus erythematosus and primary biliary cholangitis: A bidirectional Mendelian randomization study.

An association has been observed between systemic lupus erythematosus (SLE) and primary biliary cholangitis (PBC) in observational studies, however, the exact causal link remains unclear. We aim to evaluate the causal relationships between SLE and PBC through bidirectional Mendelian randomization (MR). Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from publicly accessible genome-wide association studies (GWAS) in European populations. The PBC and SLE GWAS data were obtained from the MRC IEU Open GWAS database, consisting of 24,510 and 14,267 samples, respectively. After a series of quality control and outlier removal, inverse variance weighted was used as the primary approach to evaluate the causal association between SLE and PBC. The horizontal pleiotropy and heterogeneity were examined by the MR-Egger intercept test and Cochran Q value, respectively. Seven SNPs were included to examine the causal effect of SLE on PBC. Genetically predicted SLE may increase the risk of PBC development, with an odds ratio (OR) of 1.324 (95% confidence interval [CI] 1.220 ∼ 1.437, P ˂ .001). Twenty SNPs were included to explore the causal effect of PBC on SLE. Genetically predicted PBC may increase the risk of SLE development, with an OR of 1.414 (95% CI 1.323 ∼ 1.511, P ˂ .001). Horizontal pleiotropy and heterogeneity were absent (P > .05) among SNPs. The robustness of our results was further enhanced by using the leave-one-out method. Our research has provided new insights into SLE and PBC, indicating bidirectional causal associations between the 2 diseases. These findings offer valuable contributions to future clinical studies.

Modulating Electron Transfer between Pt and MOF Support through Pd Doping Promotes Nanozyme Catalytic Efficiency.

Electron transfer is considered to be a typical parameter that affects the catalytic activity of nanozymes. However, there is still controversy regarding whether higher or lower electron transfer numbers are beneficial for improving the catalytic activity of nanozymes. To address this issue, we propose the introduction of Pd doping as an important electron regulation strategy to tune electron transfer between Pt and ZIF-8 carriers (PtxPd1@ZIF-8). We observe a volcano-shaped relationship between the electron transfer number and catalytic activity, reaching its peak at Pt4Pd1@ZIF-8. Mechanism studies indicate that as the electron transfer number from Pt to ZIF-8 carriers increases, the d-band center of the active site Pt increases, reducing the occupancy of antibonding states and enhancing the adsorption capacity of the key intermediate (*O). However, a further increase in the adsorption of *O energy makes it difficult to desorb and participate in the next reaction, thus exhibiting volcanic activity. The optimized Pt4Pd1@ZIF-8 nanozyme is applied to develop an immunoassay for the detection of zearalenone, achieving a detection limit of 0.01 µg/L, which is 6 times higher than that of the traditional enzyme-linked immunosorbent assay. This work not only reveals the potential regulatory mechanism of electron transfer on the catalytic activity of nanozymes but also improves the performance of nanozyme-based biosensors.

Dual-course dielectric barrier discharge with a novel hollow micro-holes electrode to efficiently mitigate NOx.

The effect of a novel hollow annular micro-hole electrode on the DBD de-NOx performance was investigated. The experimental results show that the hollow electrode allows the feed gas to take full advantage of the redundant heat of the electrode, thus reducing the energy consumption of the system. Subsequently, the micro-hole structure can improve the uniformity of feed gas in the plasma channel and prolong the residence time of the feed gas in the plasma channel. The reactor can also raise the temperature of the feed gas and enhance the plasma electric field. The optimum NOx removal efficiency of about 82.6% is achieved at 16 annular micro-holes. Compared to the rod electrode reactor, the novel electrode reactor shows 19.7% reduction in energy consumption and 13.2% enhancement in de-NOx efficiency. The calculations of de-NOx mechanism show that the NO2 concentration decays significantly as the feed gas residence time increases, accompanied by a slight increase in N2O concentration. The NO2 concentration marginally increases while N2O concentration slightly decreases as the increase of feed gas temperature. DBD de-NOx presents the mode of accelerated reduction of NO, essential removal of NO2, and gradual consumption of N2O with the reduced electric field increases.

The potential application and molecular mechanisms of natural products in the treatment of allergic rhinitis: A review.

BACKGROUNDS: Allergic rhinitis (AR) is a non-infectious chronic inflammation of the nasal mucosa mainly mediated by immunoglobulin E (IgE) in atopic individuals after exposure to allergens. The application of AR guideline-recommended pharmacotherapies can rapidly relieve symptoms of AR but with poor long-term efficacy, and many of these therapies have side effects. Many natural products and their derivatives have shown potential therapeutic effects on AR with fewer side effects. OBJECTIVES: This review aims to expand understanding of the roles and mechanisms of natural compounds in the treatment of AR and to highlight the importance of utilizing natural products in the treatment of AR. MATERIAL AND METHOD: We conducted a systematic literature search using PubMed, Web of Science, Google Scholar, and Clinical Trials. The search was performed using keywords including natural products, natural compounds, bioproducts, plant extracts, naturally derived products, natural resources, allergic rhinitis, hay fever, pollinosis, nasal allergy. Comprehensive research and compilation of existing literature were conducted. RESULTS: This article provided a comprehensive review of the potential therapeutic effects and mechanisms of natural compounds in the treatment of AR. We emphasized that natural products primarily exert their effects by modulating signalling pathways such as NF-κB, MAPKs, STAT3/ROR-γt/Foxp3, and GATA3/T-bet, thereby inhibiting the activation and expansion of allergic inflammation. We also discussed their toxicity and clinical applications in AR therapy. CONCLUSION: Taken together, natural products exhibit great potential in the treatment of AR. This review is also expected to facilitate the application of natural products as candidates for treating AR. Furthermore, drug discovery based on natural products has a promising prospect in AR treatment.

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ArLD) constitute the primary forms of chronic liver disease, and their incidence is progressively increasing with changes in lifestyle habits. Earlier studies have documented a correlation between the occurrence and development of prevalent mental disorders and fatty liver. AIM: To investigate the correlation between fatty liver and mental disorders, thus necessitating the implementation of a mendelian randomization (MR) study to elucidate this association. METHODS: Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog, while information on mental disorders, including Alzheimer's disease, schizophrenia, anxiety disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, multiple personality disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and schizophrenia was acquired from the psychiatric genomics consortium. A two-sample MR method was applied to investigate mediators in significant associations. RESULTS: After excluding weak instrumental variables, a causal relationship was identified between fatty liver disease and the occurrence and development of some psychiatric disorders. Specifically, the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD (OR: 5.81, 95%CI: 5.59-6.03, P < 0.01), bipolar disorder (OR: 5.73, 95%CI: 5.42-6.05, P = 0.03), OCD (OR: 6.42, 95%CI: 5.60-7.36, P < 0.01), and PTSD (OR: 5.66, 95%CI: 5.33-6.01, P < 0.01). Meanwhile, NAFLD significantly increased the risk of developing bipolar disorder (OR: 55.08, 95%CI: 3.59-845.51, P < 0.01), OCD (OR: 61.50, 95%CI: 6.69-565.45, P < 0.01), and PTSD (OR: 52.09, 95%CI: 4.24-639.32, P < 0.01). CONCLUSION: Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders, namely bipolar disorder, OCD, and PTSD, highlighting the significance of preventive measures against psychiatric disorders in patients with fatty liver disease.

Efficient and Selective Construction of 41 2 Metalla-links Using Weak C-H⋠⋠⋠Halogen Interactions.

Through a coordination-driven self-assembly method, four 4 1 2 ${4_1^2 }$ metalla-links and one tetranuclear monocycle were constructed with high selectivity and yield by adjusting the substituent species of the building blocks, as evidenced using X-ray crystallographic analysis, electrospray ionization-time-of-flight/mass spectrometry (ESI-TOF/MS), elemental analysis and detailed solution-state nuclear magnetic resonance (NMR) spectroscopy. Based on X-ray crystallographic analysis and independent gradient model analysis, a significant factor leading to the formation of 4 1 2 ${4_1^2 }$ metalla-links was the introduction of F, Cl, Br and I atoms, which generated additional weak C-H⋅⋅⋅X (X=F, Cl, Br and I) interactions. Furthermore, the dynamic conversion of 4 1 2 ${4_1^2 }$ metalla-links to monocyclic rings in methanol solution was systematically investigated using quantitative 1H NMR techniques.