TEAD4 activates PCSK9 to promote stomach adenocarcinoma cell stemness through fatty acid metabolism.

INTRODUCTION: This study attempted to investigate how PCSK9 influences the stemness of stomach adenocarcinoma (STAD) cells. METHODS: CCK-8 and sphere formation assays were used to detect cell viability and stemness. qRT-PCR and western blot were used to detect PCSK9 and TEAD4 expression. The binding relationship was verified by dual luciferase and chromatin immunoprecipitation (ChIP) assays. The effect of TEAD4 activating PCSK9 on the stemness of STAD cells was detected by bioinformatics, BODIPY 493/503, Oil red O, western blot, and kits. In vivo experiments verified the role of the TEAD4/PCSK9 axis in tumor formation in nude mice. RESULTS: PCSK9 and TEAD4 were highly expressed in STAD. PCSK9 was enriched in the FAM pathway. PCSK9 activated the fatty acid metabolism and promoted the proliferation and stemness of STAD cells. TEAD4 as a transcription factor upstream of PCSK9.Cell experiments revealed that knockdown of PCSK9 inhibited STAD cell stemness, whereas further addition of fatty acid inhibitors could attenuate the promoting effect on STAD cell stemness brought by STAD overexpression. Rescue experiments showed overexpressed PCSK9 exerted an inhibitory effect on the stemness of STAD cells brought by TEAD4 knockdown. The hypothesis that TEAD4/PCSK9 axis can promote STAD cell growth was confirmed by in vivo experiments. CONCLUSION: Transcription factor TEAD4 could activate PCSK9 to promote the stemness of STAD cells through FAM. These results added weight to the assumption that TEAD4/PCSK9 axis has the potential to be the therapeutic target that inhibits CSC in STAD.

Preparation and evaluation of a piperidinium-sulfonate based zwitterionic monolith for HILIC separation.

In this study, a novel piperidinium-sulfonate based zwitterionic hydrophilic monolith was prepared through thermally initiated co-polymerization of a piperidinium-sulfonate monomer 3-(4-((methacryloyloxy)methyl)-1-methylpiperidin-1-ium-1-yl)propane-1-sulfonate (MAMMPS), and a hydrophilic crosslinker N,N'-methylenebisacrylamide (MBA) using n-propanol and H2O as porogenic system. Satisfactory mechanical and chemical stabilities, good repeatability and high column efficiency (120,000 N/m) were obtained on the optimal monolith. The resulting poly(MAMMPS-co-MBA) monolith showed a typical HILIC retention behavior over an ACN content range between 5 and 95 %. Furthermore, this column exhibited good separation performance for various polar compounds. Compared to quaternary ammonium-sulfonate based zwitterionic hydrophilic monolith, i.e. poly(N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)ammonium betaine-co-MBA), the poly(MAMMPS-co-MBA) monolith displayed stronger retention and better selectivity for the tested phenolic and amine compounds at different pH conditions. Finally, this column was applied for the separation of six sulfonamide antibiotics, and the analytical characteristics of the method were evaluated in terms of precision, repeatability, limits of detection (LOD) and quantitation (LOQ). Overall, this study not only developed a novel HILIC monolithic column, but also proved the potential of piperidinium-sulfonate based zwitterionic chemistry as stationary phase, which further increased the structure diversity of zwitterionic HILIC stationary phases.

ImmunoPET imaging of Trop2 in patients with solid tumours.

Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours and plays a crucial role in tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68Ga-labelled nanobody tracers that can rapidly and specifically target Trop2. Of the two tracers, [68Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics in preclinical mouse models and a beagle dog. Moreover, [68Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous and differential expression in preclinical solid tumour models and ten patients with solid tumours. [68Ga]Ga-NOTA-T4 immunoPET could facilitate clinical decision-making through patient stratification and response monitoring during Trop2-targeted therapies.

A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease.

AIMS: Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. METHODS: Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. RESULTS: 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001). CONCLUSION: STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.

The effect of reward on motor learning: different stage, different effect.

Motor learning is a prominent and extensively studied subject in rehabilitation following various types of neurological disorders. Motor repair and rehabilitation often extend over months and years post-injury with a slow pace of recovery, particularly affecting the fine movements of the distal extremities. This extended period can diminish the motivation and persistence of patients, a facet that has historically been overlooked in motor learning until recent years. Reward, including monetary compensation, social praise, video gaming, music, and virtual reality, is currently garnering heightened attention for its potential to enhance motor motivation and improve function. Numerous studies have examined the effects and attempted to explore potential mechanisms in various motor paradigms, yet they have yielded inconsistent or even contradictory results and conclusions. A comprehensive review is necessary to summarize studies on the effects of rewards on motor learning and to deduce a central pattern from these existing studies. Therefore, in this review, we initially outline a framework of motor learning considering two major types, two major components, and three stages. Subsequently, we summarize the effects of rewards on different stages of motor learning within the mentioned framework and analyze the underlying mechanisms at the level of behavior or neural circuit. Reward accelerates learning speed and enhances the extent of learning during the acquisition and consolidation stages, possibly by regulating the balance between the direct and indirect pathways (activating more D1-MSN than D2-MSN) of the ventral striatum and by increasing motor dynamics and kinematics. However, the effect varies depending on several experimental conditions. During the retention stage, there is a consensus that reward enhances both short-term and long-term memory retention in both types of motor learning, attributed to the LTP learning mechanism mediated by the VTA-M1 dopaminergic projection. Reward is a promising enhancer to bolster waning confidence and motivation, thereby increasing the efficiency of motor learning and rehabilitation. Further exploration of the circuit and functional connections between reward and the motor loop may provide a novel target for neural modulation to promote motor behavior.

Determination of viable myocardium through delayed enhancement cardiac magnetic resonance imaging combined with 18F-FDG PET myocardial perfusion/metabolic imaging before CABG.

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.

A comprehensive evaluation of a polymeric zwitterionic hydrophilic monolith for nucleotide separation.

Rapid and effective separation of nucleotides (NTs) and their derivatives is crucial for studying their physiological functions. In this work, we comprehensively evaluated the separation ability of a zwitterionic hydrophilic monolith, i.e., poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine-co-N,N'-methylenebisacrylamide) (poly(SPP-co-MBA)) for NTs analysis, including its selectivity, chemical stability under extremely basic condition and compatibility with hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (HILIC-MS). The poly(SPP-co-MBA) monolith exhibited excellent chemical stability, as evidenced by the low relative standard deviation of retention time (0.16-1.05%) after 4000 consecutive injections over one month under strong alkaline elution condition (pH 10). After optimizing the separation conditions, including buffer pH and concentration, organic solvent content and column temperature, four nucleoside triphosphates, five nucleoside diphosphates and five nucleoside monophosphates were baseline separated within 7 min. Additionally, the mixtures containing one nucleoside and its corresponding mono-, di-, and triphosphates were baseline separated within only 3 min, respectively. It is good HILIC-MS compatibility was also confirmed by the satisfactory peak shape and high response of nine NTs. Overall, the proposed poly(SPP-co-MBA) monolith exhibited good mechanical stability and compatibility of HILIC-MS, making it a promising technique for NTs analysis.

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test: insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy.

After stroke, even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity, leading to reduced functional independence. Bilateral arm training has been proposed as a promising intervention to address these deficits. However, the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear, limiting the development of more targeted interventions. To address this gap, our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination. Twenty-four high-functioning patients with ischemic stroke (7 women, 17 men; mean age 64.75 ± 10.84 years) participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test, which measures unimanual and bimanual finger and hand dexterity. We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks, with bimanual tasks inducing higher cortical activation than the assembly subtask. Importantly, patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks. Notably, the observed neural response patterns varied depending on the specific subtask. In the unaffected hand task, the differences were primarily observed in the ipsilesional hemisphere. In contrast, the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task, respectively. While significant correlations were found between cortical activation and unimanual tasks, no significant correlations were observed with bimanual tasks. This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke, highlighting task-dependent neural responses. The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation. Therefore, incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes. The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.

Region-specific response of central microglial cells to sciatic nerve demyelination through sensory and motor pathways.

Peripheral nerve injury can cause changes in microglial cells on the spinal dorsal and ventral horns. This region-specific response implies that central microglial cells could be activated through both sensory and motor pathways. In order to further determine how peripheral nerve injury activates central microglial cells through neural pathways, the sciatic nerve was selected as the target for neural tract tracing and demyelination. Firstly, we used cholera toxin subunit B (CTB) to map the central sensory and motor territories of the sciatic nerve. Secondly, we applied lysophosphatidylcholine to establish the model of sciatic nerve demyelination and examined the distribution of activated microglial cells via immunofluorescence with ionized calcium-binding adapter molecule 1. It was shown that CTB labeling included the transganglionically labeled sensory afferents and retrogradely labeled somata of motor neurons along the sensory and motor pathways of the sciatic nerve ipsilateral to the injection, in which sensory afferents terminated on the gracile nucleus, Clarke's nucleus, and spinal dorsal horn, while motor neurons located on the spinal ventral horn. Consistently, after sciatic axon demyelination, the activated microglial cells were observed in the same territories as CTB-labeling, showing shortened processes and enlarged cell bodies. These results support the idea that central microglia might be activated by signals from the demyelinated sciatic nerve through both sensory and motor pathways.

Unraveling the Solvent Effect on Solid-Electrolyte Interphase Formation for Sodium Metal Batteries.

Ether-based electrolytes are considered as an ideal electrolyte system for sodium metal batteries (SMBs) due to their superior compatibility with the sodium metal anode (SMA). However, the selection principle of ether solvents and the impact on solid electrolyte interphase formation are still unclear. Herein, we systematically compare the chain ether-based electrolyte and understand the relationship between the solvation structure and the interphasial properties. The linear ether solvent molecules with different terminal group lengths demonstrate remarkably distinct solvation effects, thus leading to different electrochemical performance as well as deposition morphologies for SMBs. Computational calculations and comprehensive characterizations indicate that the terminal group length significantly regulates the electrolyte solvation structure and consequently influences the interfacial reaction mechanism of electrolytes on SMA. Cryogenic electron microscopy clearly reveals the difference in solid electrolyte interphase in various ether-based electrolytes. As a result, the 1,2-diethoxyethane-based electrolyte enables a high Coulombic efficiency of 99.9 %, which also realizes the stable cycling of Na||Na3 V2 (PO4 )3 full cell with a mass loading of ≈9 mg cm-2 over 500 cycles.

Three-dimensional visualization of the lymphatic, vascular and neural network in rat lung by confocal microscopy.

In order to demonstrate the intricate interconnection of pulmonary lymphatic vessels, blood vessels, and nerve fibers, the rat lung was selected as the target and sliced at the thickness of 100 µm for multiply immunofluorescence staining with lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), alpha smooth muscle actin (α-SMA), phalloidin, cluster of differentiation 31 (CD31), and protein gene product 9.5 (PGP9.5) antibodies. Taking the advantages of the thicker tissue section and confocal microscopy, the labeled pulmonary lymphatic vessels, blood vessels, and nerve fibers were demonstrated in rather longer distance, which was more convenient to reconstruct a three-dimensional (3D) view for analyzing their spatial correlation in detail. It was clear that LYVE-1+ lymphatic vessels were widely distributed in pulmonary lobules and closely to the lobar bronchus. Through 3D reconstruction, it was also demonstrated that LYVE-1+ lymphatic vessels ran parallel to or around the α-SMA+ venules, phalloidin+ arterioles and CD31+ capillaries, with PGP9.5+ nerve fibers traversing alongside or wrapping around them, forming a lymphatic, vascular and neural network in the lung. By this study, we provide a detailed histological view to highlight the spatial correlation of pulmonary lymphatic, vascular and neural network, which may help us for insight into the functional role of this network under the physiological and pathological conditions.

The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection.

BACKGROUND: The study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. METHOD: Twenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. RESULT: Our analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016-1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97-1, p < 0.001), and this was the best predictive value of the renal function on D7. CONCLUSIONS: Donor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.

Modulated effectiveness of rehabilitation motivation by reward strategies combined with tDCS in stroke: study protocol for a randomized controlled trial.

Background: Stroke survivors often exhibit low motivation for rehabilitation, hindering their ability to effectively complete rehabilitation training task effectively and participate in daily activities actively. Reward strategies have been identified as an effective method for boosting rehabilitation motivation, but their long-term efficacy remains uncertain. Transcranial direct current stimulation (tDCS) has been recognized as a technique that facilitates plastic changes and functional reorganization of cortical areas. Particularly, tDCS can improve the functional connectivity between brain regions associated with goal-directed behavior when applied to the left dorsolateral prefrontal cortex (dlPFC). Combing reward strategies with tDCS (RStDCS) has been shown to motivate healthy individuals to exert more effort in task performance. However, research exploring the combined and sustained effects of these strategies on rehabilitation motivation in stroke survivors is lacking. Methods and design: Eighty-seven stroke survivors with low motivation and upper extremity dysfunction will be randomized to receive either conventional treatment, RS treatment, or RStDCS treatment. The RStDCS group will receive reward strategies combined with anodal tDCS stimulation of the left dlPFC. The RS group will receive reward strategies combined with sham stimulation. The conventional group will receive conventional treatment combined with sham stimulation. tDCS stimulation is performed over 3 weeks of hospitalization, 20 min/time, five times a week. Reward strategies refers to personalized active exercise programs for patients during hospitalization and at home. Patients can voluntarily choose tasks for active exercise and self-report to the therapist so as to punch a card for points and exchange gifts. The conventional group will receive home rehabilitation instructions prior to discharge. Rehabilitation motivation, measured using RMS. RMS, FMA, FIM, and ICF activity and social engagement scale will be compared at baseline, 3 weeks, 6 weeks, and 3 months post-enrollment to evaluate patients' multifaceted health condition based on the ICF framework. Discussion: This study integrates knowledge from social cognitive science, economic behavioral science, and other relevant fields. We utilize straightforward and feasible reward strategies, combined with neuromodulation technology, to jointly improve patients' rehabilitation motivation. Behavioral observations and various assessment tools will be used to monitor patients' rehabilitation motivation and multifaceted health condition according to the ICF framework. The aim is to provide a preliminary exploration path for professionals to develop comprehensive strategies for improving patient rehabilitation motivation and facilitating a complete "hospital-home-society" rehabilitation process. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=182589, ChiCTR2300069068.

Astragaloside reduces toxic effect of periodontal ligament fibroblasts induced by lipopolysaccharide.

Periodontitis is a non-specific and chronic disease which is highly prevalent, resulting in inflammation and destruction of periodontal tissues. This study aims to explore the effect and mechanism of astragaloside on periodontitis. We used CCK-8, Western Blot, qPCR and flow cytometry to analyze cell viability, related protein and mRNA expression, and cell apoptosis. We found that AST could promote cell proliferation and reduce apoptosis induced by LPS. Besides, AST could alleviate the increased expression of COX-2 and ICAM-1 induced by LPS. MiR-26b-3P specifically targeted the 3' UTR of ICAM-1. These results indicate that AST reduces toxic effect of human periodontal ligament cells through regulating miR-26b-3P/ICAM-1, thus highlighting its protective role in periodontitis.

Exploring the bidirectional relationship between pain and mental disorders: a comprehensive Mendelian randomization study.

BACKGROUND: The close relationship between pain and mental health problems is well-known, and psychological intervention can provide an effective alternative to medication-based pain relief. However, previous studies on the connection between pain and psychological problems, the findings thus far have been inconclusive, limiting the potential for translating psychological interventions into clinical practice. To complement the gap, this study utilized genetic data and Mendelian randomization (MR) to examine the potential relationship between pain in different parts and common mental disorders. METHODS: Based on the instrumental variables selected from the Genome-wide association study summary statistics of localized pain and mental disorders, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between pain and mental disorders. The inverse-variance weighted MR method and MR-Egger were used as the primary statistical method according to the horizontal pleiotropy and heterogeneity level. We reported the odds ratio to infer the causal effect between pain and mental disorders. F statistic was calculated to measure the statistical efficacy of the analyses. RESULTS: Insomnia is causally related to the genetic susceptibility of multisite pain including head (OR = 1.09, 95% CI: 1.06-1.12), neck/shoulder (OR = 1.12, 95% CI: 1.07-1.16), back (OR = 1.12, 95% CI: 1.07-1.18) and hip (OR = 1.08, 95% CI: 1.05-1.10). Reversely, headache (OR = 1.14, 95% CI: 1.05-1.24), neck/shoulder pain (OR = 1.95, 95% CI: 1.03-3.68), back pain (OR = 1.40, 95% CI: 1.22-1.60), and hip pain (OR = 2.29, 95% CI: 1.18-4.45) promote the genetic liability of insomnia. Depression is strongly associated with the predisposition of multisite pain including headache (OR = 1.28, 95% CI: 1.08-1.52), neck/shoulder pain (OR = 1.32, 95% CI: 1.16-1.50), back pain (OR = 1.35, 95% CI: 1.10-1.66) and stomach/abdominal pain (OR = 1.14, 95% CI: 1.05-1.25), while headache (OR = 1.06, 95% CI: 1.03-1.08), neck/shoulder (OR = 1.09, 95% CI: 1.01-1.17), back (OR = 1.08, 95% CI: 1.03-1.14), and stomach/abdominal pain (OR = 1.19, 95% CI: 1.11-1.26) are predisposing factors for depression. Additionally, insomnia is associated with the predisposition of facial, stomach/abdominal, and knee pain, anxiety was associated with the predisposition of neck/shoulder and back pain, while the susceptibilities of hip and facial pain are influenced by depression, but these associations were unidirectional. CONCLUSIONS: Our results enhance the understanding of the complex interplay between pain and mental health and highlight the importance of a holistic approach to pain management that addresses both physical and psychological factors.

Association Between Visceral Fat Area and Cancer Prognosis: A Population-Based Multicenter Prospective Study.

BACKGROUND: Diverse indicators have been used to represent adipose tissue, while the relationship between body adipose mass and the prognosis of patients with cancer remains controversial. OBJECTIVE: This study aimed to explore the indicators of optimal body composition that represent body fat mass to predict risk of cancer-related mortality. METHODS: We conducted a population-based multicenter prospective cohort study of patients with initial cancer between February 2012 and September 2020. Clinical information, body composition indicators, hematologic test results, and follow-up data were collected. Body composition indicators were analyzed using principal component analysis to select the most representative indicators, and the cutoff value was set according to the optimal stratification method. The hazard ratio (HR) for mortality was calculated using Cox proportional hazards regression models. RESULTS: Among 14,018 patients with complete body composition data, visceral fat area (VFA) is a more optimal indicator for body fat content (principal component index: 0.961) than body mass index (principal component index: 0.850). The cutoff points for VFA in terms of time to mortality were 66 cm2 and 102 cm2 for gastric/esophageal cancer and other cancers, respectively. Among the 2788 patients treated systemically, multivariate analyses demonstrated that a lower VFA was associated with a higher risk of death in patients with cancer of diverse types (HR: 1.33; 95% CI: 1.08, 1.64; P = 0.007), especially gastric cancer (HR: 2.13; 95% CI: 1.3, 3.49; P = 0.003), colorectal cancer HR: 1.81; 95% CI: 1.06, 3.08; P = 0.030) and nonsmall-cell lung cancer (HR: 1.27; 95% CI: 1.01, 1.59; P = 0.040). CONCLUSION: VFA is an independent prognostic indicator of muscle mass in patients with diverse types of cancer, particularly gastric, colorectal, and nonsmall-cell lung cancers. TRIAL REGISTRATION NUMBER: ChiCTR1800020329.

High-entropy Electrolyte Enables High Reversibility and Long Lifespan for Magnesium Metal Anodes.

The stable cycling of Mg-metal anodes is limited by several problems, including sluggish electrochemical kinetics and passivation at the Mg surface. In this study, we present a high-entropy electrolyte composed of lithium triflate (LiOTf) and trimethyl phosphate (TMP) co-added to magnesium bis(trifluoromethane sulfonyl)imide (Mg(TFSI)2 /1,2-dimethoxyethane (DME) to significantly improve the electrochemical performance of Mg-metal anodes. The as-formed high-entropy Mg2+ -2DME-OTf- -Li+ -DME-TMP solvation structure effectively reduced the Mg2+ -DME interaction in comparison with that observed in traditional Mg(TFSI)2 /DME electrolytes, thereby preventing the formation of insulating components on the Mg-metal anode and promoting its electrochemical kinetics and cycling stability. Comprehensive characterization revealed that the high-entropy solvation structure brought OTf- and TMP to the surface of the Mg-metal anode and promoted the formation of a Mg3 (PO4 )2 -rich interfacial layer, which is beneficial for enhancing Mg2+ conductivity. Consequently, the Mg-metal anode achieved excellent reversibility with a high Coulombic efficiency of 98 % and low voltage hysteresis. This study provides new insights into the design of electrolytes for Mg-metal batteries.

Highly Efficient Solar-Driven Dry Reforming of Methane on a Rh/LaNiO3 Catalyst through a Light-induced Metal-To-Metal Charge Transfer Process.

As an energy-saving and green method, solar-driven dry reforming of methane (DRM) is expected to introduce new activation processes and prevent sintering and coking of the catalysts. However, it still lacks an efficient way to coordinate the regulation of activation of reactants and lattice oxygen migration. In this study, Rh/LaNiO3 is designed as a highly efficient photothermal catalyst for solar-driven DRM, which performs production rates of 452.3 mmol h-1  gRh -1 for H2 and 527.6 mmol h-1  gRh -1 for CO2 under a light intensity of 1.5 W cm-2 , with an excellent stability. Moreover, a remarkable light-to-chemical energy efficiency (LTCEE) of 10.72% is achieved under a light intensity of 3.5 W cm-2 . The characterizations of surface electronic and chemical properties and theoretical analysis demonstrate that strong adsorption for CH4 and CO2 , light-induced metal-to-metal charge transfer (MMCT) process and high oxygen mobility together bring Rh/LaNiO3 excellent performance for solar-driven DRM.

Selection of Automated Platelet Counting Methods Based on Mean Platelet Volume (MPV).

BACKGROUND: Impedance-based detection and optic detection with fluorescence are common platelet counting methods used by modern hematology analyzers. There are few studies to compare the accuracy of platelet counts using these methods in case of increased MPV. METHODS: Sixty patients with immune-related thrombocytopenia (IRTP) and 60 healthy controls were included. Platelet counts were obtained by BC-6900 analyzer using impedance detection (PLT-I) and optic detection with fluorescence (PLT-O). Flow cytometry was used as the reference (FCM-ref). RESULTS: The platelet counts in patients using PLT-I were significantly lower than those using PLT-O or FCM-ref by an average of 13.3%. The platelet counts by PLT-O compared to FCM-ref were not statistically significant. MPV inversely affected the platelet counts. When MPV was < 13 fL, platelet counts by all three methods were not statistically different. When MPV was ≥ 13 fL, platelet counts by PLT-I were significantly lower (-15.8%) than those by PLT-O or FCM-ref. Furthermore, when MPV was ≥ 15 fL, platelet counts using PLT-I were further decreased (-23.6%) compared to the counts obtained by PLT-O or FCM-ref. CONCLUSIONS: The platelet counts by PLT-O in patients with IRTP is as accurate as by FCM-ref. When MPV is < 13 fL, platelet counts by all three methods are comparable. However, when MPV is ≥ 13 fL, platelet counts by PLT-I can erroneously decrease by as many as 23.6%. Therefore, in case of IRTP, or any cases when MPV ≥ 13 fL, platelet counts obtained by PLT-I method should be carefully checked by other methods, such as PLT-O to ensure a more accurate platelet count.