Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases.

Rationale: Sustained activation of lung fibroblasts and the resulting oversynthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, and is also a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined. Objectives: The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate or measure the amounts of activated fibroblasts in ILD lungs quantitatively. Methods: FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed. Measurements and Main Results: Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD. Conclusions: Our results strongly support that in vitro and in vivo detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.

Association of sleep duration and risk of mental disorder: a systematic review and meta-analysis.

BACKGROUND: The effects of sleep duration on the development of mental illness remain controversial. Therefore, it is necessary to identify the effects of long or short sleep duration on psychological disorders, which could reveal new ways for preventing and treating mental health conditions cheaply. METHODS: Identifying published papers was accomplished by using the following five English databases on March 16, 2022: PubMed, MEDLINE, Embase, Web of Science databases, and Scopus. Cross-sectional and cohort studies were considered if they evaluated the association of sleep duration with all kinds of mental illness in adults. We excluded case reports, editorials, narrative reviews, and studies without detailed information on sleep duration. Summary effect-size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. Mantel-Haenszel's random-effects model was used to estimate the inconsistency index (I2) and Tau2 index (measurement of heterogeneity). RESULTS: A total of 52 studies were included in this analysis, consisting of 14 cohort studies and 38 cross-sectional studies. These studies involved a combined sample size of 1,407,891 participants who met the inclusion criteria. Cohort (adjusted RR = 1.42, 95% CI: 1.26-1.60, P < .001, I2 = 37.6%, Tau2 = 0.014) and cross-sectional studies (adjusted OR = 1.67, 95% CI: 1.57-1.77, P < .001, I2 = 79.7%, Tau2 = 0.060) concluded that short sleep duration increased mental disorder risks. The same conclusions were acquired in the subgroup analysis, especially for depression (adjusted RR = 1.43, 95% CI: 1.24-1.65, P < .001, I2 = 80.4%, Tau2 = 0.082), anxiety (adjusted RR = 1.30, 95% CI: 1.04-1.63, P = .002, I2 = 0.0%, Tau2 = 0.000), and PTSD (adjusted RR = 1.35, 95% CI: 1.04-1.76, P = .022, I2 = 24.1%, Tau2 = 0.013) in cohort studies. The results of subgroup analysis indicated that long sleep duration was not a risk factor for depression (adjusted RR = 1.15, 95% CI: 0.98-1.34, P = .088, I2 = 63.4%, Tau2 = 0.045) and anxiety (adjusted RR = 1.37, 95% CI: 0.93-2.03, P = .114, I2 = 0.0%, Tau2 = 0.000). CONCLUSIONS: Short sleep duration, not long sleep duration, is an independent predictor of developing mental disorders, particularly anxiety and depression.

Discovery of marine phidianidine-based Nrf2 activators and their potential against oxLDL- and HG-induced injury in HUVECs.

One effective strategy for treating atherosclerosis is to inhibit the injury of vascular endothelial cells (VECs) induced by oxidized low-density lipoprotein (oxLDL) and high glucose (HG). This study synthesized and evaluated a series of novel Nrf2 activators derived from the marine natural product phidianidine for their ability to protect human umbilical VECs against oxLDL- and HG-induced injury. The results of in vitro bioassays demonstrated that compound D-36 was the most promising Nrf2 activator, effectively inhibiting the apoptosis of HUVECs induced by oxLDL and HG. Furthermore, Nrf2 knockdown experiments confirmed that compound D-36 protected against oxLDL- and HG-induced apoptosis in HUVECs by activating the Nrf2 pathway. These findings provide important insights into a new chemotype of marine-derived Nrf2 activators that could potentially be optimized to develop effective anti-atherosclerosis agents.

What impacts ecosystem services in tropical coastal tourism cities? A comparative case study of Haikou and Sanya, China.

The ecological environment of tourism-oriented towns is attracting increasing attention. Taking the cities of Haikou and Sanya as examples, we examined changes in six ecosystem services (ES), including water conservation (WC), crop production (CP), soil retention (SR), carbon storage (CS), habitat quality (HQ), and tourism recreation (TR) from 2005 to 2020. From the three perspectives of geographical environment, socioeconomic development, and tourism development force, 14 indicators were chosen to examine the impact on ES. Except for Haikou's TR, the other ES of Haikou and Sanya showed a decreasing trend from 2005 to 2020. The values of six ES were lower in coastal zones than in noncoastal zones, which were more obvious in Sanya. Specifically, the areas of low value in Sanya were concentrated in the coastal region, and the areas with low value in Haikou were primarily distributed in blocks along the coast and in bands or points in the central and southern areas. From the perspective of influencing factors, the natural environmental factors dominate in Haikou, followed by the socio-economic factors and finally the tourism development factors, while the natural environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socio-economic factors. We provided recommendations for sustainable tourism development in Haikou and Sanya. This study has significant implications for both integrated management and scientific decision-making to enhance the ES of tourism destinations.

Construction of 131I-RGDyC-PEG-PAMAM-DTX targeted drug delivery system and study of its physicochemical properties and biological activity.

OBJECTIVE: To construct a novel targeted drug delivery nanoprobe: iodine-131-arginine-glycine-aspartate-tyrosine-cysteine peptide-polyethylene glycol-fifth generation polyamide-amine-docetaxel (131I-RGDyC-PEG-PAMAM-DTX) and to investigate its physicochemical properties and biological activity. MATERIALS AND METHODS: Docetaxel was wrapped by solvent volatilization method, and the regression curve of DTX was constructed by high-performance liquid chromatography to determine its drug loading. The particle size of RGDyC-PEG-PAMAM-DTX was detected by dynamic light scattering. The 131I labeling was performed by a chloramine-T method and purified by Sephadex-G50 column chromatography, and it is in vitro stability and lipid-water partition coefficient was investigated. The cytotoxicity of RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX on A549 cells in vitro was detected by Cell Counting Kit-8 assay. RESULTS: Arginine-glycine-aspartate-tyrosine-cysteine peptide-PEG-PAMAM-DTX was successfully prepared by solvent volatilization with a loading capacity of about 44µg/mg. The average particle size of RGDyC-PEG-PAMAM-DTX was 57.8nm; the labeling rate of 131I-RGDyC-PEG-PAMAM-DTX by the chloramine-T method was 74.09%-76.09%, and the radiochemical purity was 88.9%-92.6% after purification. The in vitro stability showed that the radiochemical purity was above 80% after 72h in fetal bovine serum and PBS buffer (25oC and 37oC).CCK-8 assay showed that RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX had more pronounced cytotoxic effects than free DTX and 131I. CONCLUSION: Iodine-131-RGDyC-PEG-PAMAM-DTX has good physicochemical properties and apparent cytotoxic effectsandis expected to be used in treating tumors.

Design, synthesis and biological evaluation of marine phidianidine-inspired derivatives against oxidized ldl-induced endothelial injury by activating Nrf2 anti-oxidation pathway.

Inhibition of oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cell (VEC) injury is one of the effective strategies for treating atherosclerosis. In the present study, a series of novel marine phidianidine-inspired indole-1,2,4-oxadiazoles was designed, synthesized, and evaluated for their effects against oxLDL-induced injury in VECs. Among them, compound D-6, displaying the most effective protective activity, was found to inhibit oxLDL-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. Mechanistic studies showed that D-6 could trigger Nrf2 nuclear translocation, subsequently resulting in increased expression of Nrf2 target gene HO-1. Meanwhile, D-6 suppressed the increase of ROS level and nuclear translocation of NF-κB induced by oxLDL. Importantly, Nrf2 knockdown attenuated the inhibition effects of D-6 on oxLDL-induced apoptosis, ROS production and NF-κB nuclear translocation. Collectively, our studies demonstrated that compound D-6 protected against oxLDL-induced endothelial injury by activating Nrf2/HO-1 anti-oxidation pathway.

SARS-CoV-Related Pandemic Outbreaks and Mental Disorder Risk.

ABSTRACT: This study aimed to quantify the association between exposure to pandemic outbreaks and psychological health via a comprehensive meta-analysis. Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates were expressed as odds ratio (OR) with 95% confidence interval (CI). Data from 22 articles, involving 40,900 persons, were meta-analyzed. Overall analyses revealed a significant association of exposing to SARS-CoV-related pandemics with human mental health (OR, 1.32; 95% CI, 1.24-1.40; p < 0.001). Subgroup analyses showed that anxiety (OR, 1.37; 95% CI, 1.19-1.58; p < 0.001), depression (OR, 1.28; 95% CI, 1.15-1.42; p < 0.001), posttraumatic stress (OR, 1.36; 95% CI, 1.17-1.58; p < 0.001), and psychological distress (OR, 1.25; 95% CI, 1.11-1.40; p < 0.001) were all obviously related to pandemic diseases. In the context of infectious disease outbreaks, the mental health of general populations is clearly vulnerable. Therefore, all of us, especially health care workers, need special attention and psychological counseling to overcome pandemic together.

Do socio-economic factors matter? A comprehensive evaluation of tourism eco-efficiency determinants in China based on the Geographical Detector Model.

Constructed on the total-factor analysis framework, this paper develops a comprehensive evaluation system and adopts the Super-SBM model to both analyze and enunciate the characteristics of tourism eco-efficiency in China during 2000-2017. This paper also identifies the determinants associated with spatial differentiation of tourism eco-efficiency by employing a novel geographical technique, namely the Geographical Detector Model. The results indicate that the tourism eco-efficiency exhibits great potential for growth. Besides, pure technical efficiency drives the optimized development of eco-efficiency. Also, there is significant spatial variations in eco-efficiency across different provinces and regions in China. Urbanization contributes to tourism eco-efficiency remarkably, followed by openness, technical level, economic scale, industrial structure, capital effect, environmental regulation, and tourism growth. The relational interrelations of tourism eco-efficiency determinants are the bi-enhancement and the nonlinear-enhancement interactions. The implications of research findings are discussed and may be applied to a multitude of corporate environmental-economic management scenarios.

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status.

Forty-seven samples of peripheral blood mononuclear cells from four groups of coronavirus disease (COVID)-19 patients (mild, severe, convalescent, retesting-positive) and healthy controls were applied to profile the immune repertoire of COVID-19 patients in acute infection or convalescence by transcriptome sequencing and immune-receptor repertoire (IRR) sequencing. Transcriptome analyses showed that genes within principal component group 1 (PC1) were associated with infection and disease severity whereas genes within PC2 were associated with recovery from COVID-19. A "dual-injury mechanism" of COVID-19 severity was related to an increased number of proinflammatory pathways and activated hypercoagulable pathways. A machine-learning model based on the genes associated with inflammatory and hypercoagulable pathways had the potential to be employed to monitor COVID-19 severity. Signature analyses of B-cell receptors (BCRs) and T-cell receptors (TCRs) revealed the dominant selection of longer V-J pairs (e.g., IGHV3-9-IGHJ6 and IGHV3-23-IGHJ6) and continuous tyrosine motifs in BCRs and lower diversity of TCRs. These findings provide potential predictors for COVID-19 outcomes, and new potential targets for COVID-19 treatment.

Design, synthesis and biological evaluation of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives as α-glucosidase inhibitors.

In this present study, a series of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives against α-glucosidase were designed and synthesized, and their biological activities were evaluated in vitro and in vivo. Most of the designed analogues exhibited better inhibitory activity than the marketed acarbose, especially the most potent compound 7 with an IC50 value of 9.26 ± 1.84 µM. The direct binding of 7 and 8 with α-glucosidase was confirmed by fluorescence quenching experiments, and the kinetic and molecular docking studies revealed that 7 and 8 inhibited α-glucosidase in a non-competitive manner. Cytotoxicity bioassay indicated compounds 7 and 8 were non-toxic towards LO2 and HepG2 at 100 µM. Furthermore, both compounds were demonstrated to have in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-treated rats.

Discovery of new 2-phenyl-1H-benzo[d]imidazole core-based potent α-glucosidase inhibitors: Synthesis, kinetic study, molecular docking, and in vivo anti-hyperglycemic evaluation.

In the present study, a series of 2-phenyl-1H-benzo[d]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1H-benzo[d]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a, and the most promising inhibitors were found to be compounds 15o and 22d with IC50 values of 2.09 ± 0.04 and 0.71 ± 0.02 µM, respectively. Fluorescence quenching experiment confirmed the direct binding of compounds 15o and 22d with α-glucosidase. Kinetic study revealed that both compounds were non-competitive inhibitors, that was consistent with the result of molecular docking studies where they located at the allosteric site of the enzyme. Cell viability evaluation demonstrated the non-cytotoxicity of 15o and 22d against LO2 cells. Furthermore, the in vivo pharmacodynamic study revealed that compound 15o showed significant hypoglycemic activity and improved oral sucrose tolerance, comparable to the positive control acarbose.

Novel tetrahydrobenzo[b]thiophen-2-yl)urea derivatives as novel α-glucosidase inhibitors: Synthesis, kinetics study, molecular docking, and in vivo anti-hyperglycemic evaluation.

α-Glucosidase inhibitors, which can inhibit the digestion of carbohydrates into glucose, are one of important groups of anti-type 2 diabetic drugs. In the present study, we report our effort on the discovery and optimization of α-glucosidase inhibitors with tetrahydrobenzo[b]thiophen-2-yl)urea core. Screening of an in-house library revealed a moderated α-glucosidase inhibitors, 5a, and then the following structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased inhibitory activity against α-glucosidase than the parental compound 5a (IC50 of 26.71 ± 1.80 µM) and the positive control acarbose (IC50 of 258.53 ± 1.27 µM). Among them, compounds 8r (IC50 = 0.59 ± 0.02 µM) and 8s (IC50 = 0.65 ± 0.03 µM) were the most potent inhibitors, and showed selectivity over α-amylase. The direct binding of both compounds with α-glucosidase was confirmed by fluorescence quenching experiments. Kinetics study revealed that these compounds were non-competitive inhibitors, which was consistent with the molecular docking results that compounds 8r and 8s showed high preference to bind to the allosteric site instead of the active site of α-glucosidase. In addition, compounds 8r and 8s were not toxic (IC50 > 100 µM) towards LO2 and HepG2 cells. Finally, the in vivo anti-hyperglycaemic activity assay results indicated that compounds 8r could significantly decrease the level of plasma glucose and improve glucose tolerance in SD rats treated with sucrose. The present study provided the tetrahydrobenzo[b]thiophen-2-yl)urea chemotype for developing novel α-glucosidase inhibitors against type 2 diabetes.

Gastric emptying of preoperative drinks is slower in adults with chronic energy deficiency: A 2 hour cross-over study among Chinese.

BACKGROUND AND OBJECTIVES: To investigate the effects of oral preoperative regimens on gastric emptying time in relation to BMI in Chinese adults. METHODS AND STUDY DESIGN: The enrolled 56 adults were divided into three groups (normal-weight, underweight, and overweight) and completed a regimen of two drinks after a 2-week interval. After drinking a carbohydrate regimen (CD, 50 g carbohydrates) or a carbohydrate glutamine regimen (CGD, 44 g carbohydrates and 6 g glutamine) labelled with 99mTc-DTPA (99mTc-diethylenetriaminepentaacetic acid), gastric emptying times T50 and T90 were measured using a curve derived from scintigraphic images. RESULTS: T50 and T90 had no significant difference between the CD and CGD regimens. T50 was significantly delayed in the underweight participants (BMI <18.5 kg/m2, as Chronic Energy Deficiency, CED) compared with the normal-weight participants after drinking CD (p=0.003) or CGD (p=0.002), as well as T90 after CD (p=0.019). There was no difference in glucose concentrations between the three groups. There are negative correlations between body weight and gastric emptying time T50 (r=-0.461, p=0.016) or T90 (r=-0.553, p=0. 003) after drinking CD, as well as T50 (r=-0.553, p=0.003) after drinking CGD. CONCLUSIONS: Underweight adults should be careful to take oral preoperative regimens 2 hours before surgery and consider reducing the volume because of a slower gastric emptying rate.

Risk Interval of Complete Blood Counts May be Closely Associated with Bone Mineral Density in the Elderly Chinese Population.

BACKGROUND: Accumulating research suggests that hematopoiesis and bone metabolism are interconnected. Several studies have investigated the partial indexes of peripheral blood counts related to bone mineral density (BMD). The aim of this study was to investigate the associations between all of the parameters, especially the risk interval of complete blood counts (CBC) and BMD in a sample of elderly subjects aged >70 years. METHODS: Three hundred and eighty-six subjects aged > 70 years in our hospital were enrolled in a cross-sectional study and underwent BMD measurement along with a CBC test. Patients were divided into two groups: "at least osteopenia" (T-score < -1) and a normal group (T-score ≥ -1). The clinicopathological characteristics, CBC parameters, and BMD were analyzed between the two groups. We performed a supervised discretization (using a conditional inference tree algorithm) to find the risk interval for the continuous variables, especially for CBC parameters, and bootstrap multivariable logistic regression to estimate the odds of CBC parameters associated with BMD. RESULTS: A total of 248 subjects were included in the study and divided into the normal (n = 43) and "at least osteopenia" groups (n = 205). Subjects in the "at least osteopenia" group had varying degrees of decreases in white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), platelet volume distribution width (PDW) mean platelet volume (MPV), eosinophils, and lymphocytes, and had increases in platelets (PLTs). MCHC, WBC, RBC, PDW, MPV, Hb, and lymphocytes were successfully divided into two (low and high) intervals. Bootstrap logistic regression showed that low levels of body mass index (BMI) [(11.88, 23.53); OR: 4.07; p < 0.0001], lymphocytes [(0.54, 2.3); OR: 3.95; p < 0.0001] and PDW [(8.5, 12.7); OR: 2.44; p < 0.0001] along with being female and older age [(72, 97); OR: 2.16; p < 0.0001] were significantly associated with BMD as risk factors. CONCLUSIONS: The elderly with BMD loss tended to show an abnormal sign in the CBC test. Low levels of lymphocytes and PDW may contribute to the evaluation of osteoporosis risk in the elderly. Bone remodeling and hematopoiesis may have stronger associations and interactions than has been previously recognized.

The influence of environmental background on tourists' environmentally responsible behaviour.

Previous research on the environmentally responsible behaviour (ERB) of tourists has primarily focused on the personal psychological factors of tourists. However, the studies overlook the effect of contextual factors of a tourist site. According to the broken window theory, a disorderly, unkempt environment might lead more people to be involved in environmental destruction, which would form a vicious cycle. Therefore, it can be deduced that the environmental background (EB) of a tourist site is an important contextual factor. In this paper, the effect of the EB of a tourist site on the ERB was examined by the theory of planned behaviour (TPB) adopting structural equation model (SEM) multi-group analysis (MGA). The results show the following: first, both the attitude toward environmental behaviour (ATT) of tourists and their subjective norm (SN) have a positive impact on the environmentally responsible behavioural intention (ERBI) of tourists. In addition, perceived behavioural control (PBC) exerts a remarkable influence on the ERB of tourists and their behavioural intention. Second, the relationship between the ERBI and ERB of tourists is positively regulated by the EB of a tourist site. Additionally, this paper presents policy proposals for the environmental management of tourist sites.

Spatio-temporal modeling of connectome-scale brain network interactions via time-evolving graphs.

Many recent literature studies have revealed interesting dynamics patterns of functional brain networks derived from fMRI data. However, it has been rarely explored how functional networks spatially overlap (or interact) and how such connectome-scale network interactions temporally evolve. To explore these unanswered questions, this paper presents a novel framework for spatio-temporal modeling of connectome-scale functional brain network interactions via two main effective computational methodologies. First, to integrate, pool and compare brain networks across individuals and their cognitive states under task performances, we designed a novel group-wise dictionary learning scheme to derive connectome-scale consistent brain network templates that can be used to define the common reference space of brain network interactions. Second, the temporal dynamics of spatial network interactions is modeled by a weighted time-evolving graph, and then a data-driven unsupervised learning algorithm based on the dynamic behavioral mixed-membership model (DBMM) is adopted to identify behavioral patterns of brain networks during the temporal evolution process of spatial overlaps/interactions. Experimental results on the Human Connectome Project (HCP) task fMRI data showed that our methods can reveal meaningful, diverse behavior patterns of connectome-scale network interactions. In particular, those networks' behavior patterns are distinct across HCP tasks such as motor, working memory, language and social tasks, and their dynamics well correspond to the temporal changes of specific task designs. In general, our framework offers a new approach to characterizing human brain function by quantitative description for the temporal evolution of spatial overlaps/interactions of connectome-scale brain networks in a standard reference space.

[Application of γ imaging in chromatographic separation and protein molecular site density determination].

We in this study measured the site density of E-selectin in order to explore the practical pliability using radionuclide labeling method and γ-imaging of single photon emission computer tomography (SPECT). This method required labeling of antibody with 125I using Indogen method and binding of the labeled antibody to E-selectin. Labeled E-selectin was separated and purified in a Sephadex G25 column. The different fractions of the eluants were imaged, analyzed and quantified with SPECT method. For measuring the saturation curve of E-selectin, 130 µL of E-selectin solution with different concentrations were added in a 48-well plate and incubated overnight at 4℃. After incubation, 130 µL of labeled antibody solution were added and kept incubated for 30 min. The resulted mixture was washed, and the radioactivity in each sample was detected by SPECT. The levels of radioactivity were translated to site densities, and were used to plot a standard curve. The labeled product was quantitatively analyzed with SPECT. The labeling rate of E-selectin was 78%. The saturation curve of different concentration samples showed that when the concentration was in the concentration range of 0-1 mg/mL, the standard curve was y=6 045.7 x-51.166, R2=0.997 9. Based on this finding, it could be concluded that γ-imaging is an important tool for analysis of radiolabeled product and determination of site density.

Anti-LGI1 Antibody-Associated Encephalitis Misdiagnosed as Schizophrenia: A Case Report.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis is a rare but clinically significant form of autoimmune encephalitis, predominantly affecting middle-aged men. Its heterogeneous clinical presentation often leads to misdiagnosis, commonly as other neurological or psychiatric disorders. This report details the case of a 46-year-old male who initially presented with depressive symptoms, personality changes, and visual hallucinations. Over time, his condition progressed to include memory impairment, disorganized behavior, and seizures. Initially misdiagnosed with schizophrenia, the correct diagnosis of LGI1 antibody-associated encephalitis was eventually established through positive serum and cerebrospinal fluid (CSF) tests for LGI1 antibodies. Neuroimaging findings revealed characteristic bilateral temporal lobe lesions. The patient demonstrated marked improvement following treatment with methylprednisolone and intravenous immunoglobulin, ultimately achieving significant recovery. This case highlights the critical importance of comprehensive antibody testing and neuroimaging in patients presenting with nonspecific psychiatric and neurological symptoms to prevent misdiagnosis and delays in appropriate treatment. The article also reviews the pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies for LGI1 antibody-associated encephalitis, aiming to enhance clinical awareness and optimize patient outcomes.

Synthesis and biological evaluation of 1-phenyl-tetrahydro-ß-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents.

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.

Research on carbon dioxide capture materials used for carbon dioxide capture, utilization, and storage technology: a review.

In recent years, climate change has increasingly become one of the major challenges facing mankind today, seriously threatening the survival and sustainable development of mankind. Dramatically increasing carbon dioxide concentrations are thought to cause a severe greenhouse effect, leading to severe and sustained global warming, associated climate instability and unwelcome natural disasters, melting glaciers and extreme weather patterns. The treatment of flue gas from thermal power plants uses carbon capture, utilization, and storage (CCUS) technology, one of the most promising current methods to accomplish significant CO2 emission reduction. In order to implement the technological and financial system of CO2 capture, which is the key technology of CCUS technology and accounts for 70-80% of the overall cost of CCUS technology, it is crucial to create more effective adsorbents. Nowadays, with the development and application of various carbon dioxide capture materials, it is necessary to review and summarize carbon dioxide capture materials in time. In this paper, the main technologies of CO2 capture are reviewed, with emphasis on the latest research status of CO2 capture materials, such as amines, zeolites, alkali metals, as well as emerging MOFs and carbon nanomaterials. More and more research on CO2 capture materials has used a variety of improved methods, which have achieved high CO2 capture performance. For example, doping of layered double hydroxides (LDH) with metal atoms significantly increases the active site on the surface of the material, which has a significant impact on improving the CO2 capture capacity and performance stability of LDH. Although many carbon capture materials have been developed, high cost and low technology scale remain major obstacles to CO2 capture. Future research should focus on designing low-cost, high-availability carbon capture materials.