Analysis of the Haematological Phenotype and Molecular Characteristics of Rare Abnormal Haemoglobin.

BACKGROUND: Haemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China. METHODS: Peripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High-performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing. RESULTS: The research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg. CONCLUSION: We confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics.

Meta-analysis of effectiveness and safety of proteasome inhibitor-dependent maintenance treatment for multiple myeloma a systematic review.

Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01). Conclusion: The study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention.

A meta-analysis of the relationship between metacognition and academic achievement in mathematics: From preschool to university.

Many studies have explored the relationship between metacognition and academic achievement in mathematics, but the results vary. In this study, meta-analysis was used to explore this relationship between metacognition and academic achievement in mathematics and influencing factors. According to the literature search, a total of 147 studies (1986-2024) and 338 independent samples met the inclusion criteria (n = 698,096). The results revealed metacognition was significantly positively correlated with academic achievement in mathematics, r = 0.32, 95 % CI [0.30, 0.34], Z = 28.49. Moreover, the moderating effects of age, domain, and culture were significant (p < 0.01). In conclusion, Metacognition is closely associated with academic achievement in mathematics but also that age, domain, and culture have a considerable impact on their relationship. More specifically, the degree of correlation between metacognition and academic achievement in mathematics was on the rise from preschool to high school, while it was lower in college. Compared with general field metacognition, mathematical metacognition is more closely linked to mathematics academic achievement. Lastly, compared with British and American countries, Chinese metacognition was more closely related to academic achievement in mathematics.

Research fronts and researchers of World Journal of Psychiatry in 2023: A visualization and analysis of mapping knowledge domains.

BACKGROUND: In the rapidly evolving landscape of psychiatric research, 2023 marked another year of significant progress globally, with the World Journal of Psychiatry (WJP) experiencing notable expansion and influence. AIM: To conduct a comprehensive visualization and analysis of the articles published in the WJP throughout 2023. By delving into these publications, the aim is to determine the valuable insights that can illuminate pathways for future research endeavors in the field of psychiatry. METHODS: A selection process led to the inclusion of 107 papers from the WJP published in 2023, forming the dataset for the analysis. Employing advanced visualization techniques, this study mapped the knowledge domains represented in these papers. RESULTS: The findings revealed a prevalent focus on key topics such as depression, mental health, anxiety, schizophrenia, and the impact of coronavirus disease 2019. Additionally, through keyword clustering, it became evident that these papers were predominantly focused on exploring mental health disorders, depression, anxiety, schizophrenia, and related factors. Noteworthy contributions hailed authors in regions such as China, the United Kingdom, United States, and Turkey. Particularly, the paper garnered the highest number of citations, while the American Psychiatric Association was the most cited reference. CONCLUSION: It is recommended that the WJP continue in its efforts to enhance the quality of papers published in the field of psychiatry. Additionally, there is a pressing need to delve into the potential applications of digital interventions and artificial intelligence within the discipline.

Effect of Pretreatments on the Chemical, Bioactive and Physicochemical Properties of Cinnamomum camphora Seed Kernel Extracts.

Cinnamomum camphora seed kernels (CCSKs) are rich in phytochemicals, especially plant extracts. Phytochemicals play a vital role in therapy due to their strong antioxidant and anti-inflammatory activities. Extracts from CCSK can be obtained through multiple steps, including pretreatment, extraction and purification, and the purpose of pretreatment is to separate the oil from other substances in CCSKs. However, C. camphora seed kernel extracts (CKEs) were usually considered as by-products and discarded, and their potential bioactive values were underestimated. Additionally, little has been known about the effect of pretreatment on CKE. This study aimed to investigate the effects of pretreatment methods (including the solvent extraction method, cold pressing method, aqueous extraction method and sub-critical fluid extraction method) on the extraction yields, phytochemical profiles, volatile compounds and antioxidant capacities of different CKE samples. The results showed that the CKE samples were rich in phenolic compounds (15.28-20.29%) and alkaloids (24.44-27.41%). The extraction yield, bioactive substances content and in vitro antioxidant capacity of CKE pretreated by the sub-critical fluid extraction method (CKE-SCFE) were better than CKEs obtained by other methods. CKE pretreated by the solvent extraction method (CKE-SE) showed the best lipid emulsion protective capacity. Moreover, the volatile substances composition of the CKE samples was greatly influenced by the pretreatment method. The results provided a fundamental basis for evaluating the quality and nutritional value of CKE and increasing the economic value of by-products derived from CCSK.

Prognostic heterogeneity of Ki67 in non-small cell lung cancer: A comprehensive reappraisal on immunohistochemistry and transcriptional data.

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.

Prediction of Vacuum Ultraviolet/Ultraviolet Gas-Phase Absorption Spectra Using Molecular Feature Representations and Machine Learning.

Ultraviolet (UV) absorption spectroscopy is a widely used tool for quantitative and qualitative analyses of chemical compounds. In the gas phase, vacuum UV (VUV) and UV absorption spectra are specific and diagnostic for many small molecules. An accurate prediction of VUV/UV absorption spectra can aid the characterization of new or unknown molecules in areas such as fuels, forensics, and pharmaceutical research. An alternative to quantum chemical spectral prediction is the use of artificial intelligence. Here, different molecular feature representation techniques were used and developed to encode chemical structures for testing three machine learning models to predict gas-phase VUV/UV absorption spectra. Structure data files (.sdf) and VUV/UV absorption spectra for 1397 volatile and semivolatile chemical compounds were used to train and test the models. New molecular features (termed ABOCH) were introduced to better capture pi-bonding, aromaticity, and halogenation. The incorporation of these new features benefited spectral prediction and demonstrated superior performance compared to computationally intensive molecular-based deep learning methods. Of the machine learning methods, the use of a Random Forest regressor returned the best accuracy score with the shortest training time. The developed machine learning prediction model also outperformed spectral predictions based on the time-dependent density functional theory.

The characteristics and environmental significance of BVOCs released by aquatic macrophytes.

Biogenic volatile organic compounds (BVOCs) emitted by plants serve crucial biological functions and potentially impact atmospheric environment and global carbon cycling. Despite their significance, BVOC emissions from aquatic macrophytes have been relatively understudied. In this study, for the first time we identified there were 68 major BVOCs released from 34 common aquatic macrophytes, and these compounds referred to alcohols, aldehydes, alkanes, alkenes, arenes, ethers, furans, ketones, phenol. For type of BVOC emissions from different life form and phylogenetic group of aquatic macrophytes, 34 of the 68 BVOCs from emergent and submerged macrophytes are classified into alkene and alcohol compounds, over 50% BVOCs from dicotyledon and monocotyledon belong to alcohol and arene compounds. Charophyte and pteridophyte emitted significantly fewer BVOCs than dicotyledon and monocotyledon, and each of them only released 12 BVOCs. These BVOCs may be of great importance for the growth and development of macrophytes, because many BVOCs, such as azulene, (E)-ß-farnesene, and dimethyl sulfide are proved to play vital roles in plant growth, defense, and information transmission. Our results confirmed that both life form and phylogenetic group of aquatic macrophytes had significantly affected the BVOC emissions form macrophytes, and suggested that the intricate interplay of internal and external factors that shape BVOC emissions from aquatic macrophytes. Thus, further studies are urgently needed to investigate the influence factors and ecological function of BVOCs released by macrophytes within aquatic ecosystem.

Association between the atherogenic index of plasma and left ventricular hypertrophy in patients with obstructive sleep apnea: a retrospective cross-sectional study.

BACKGROUND: The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients. METHODS: This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C). RESULTS: Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P < 0.05). Furthermore, AIP was independently associated with LVMIh2.7 according to multivariate linear regression model (ß = 0.125, P = 0.001). Notably, AIP remained independently associated with an elevated risk of LVH [odds ratio (OR) = 1.317 per 1 standard deviation (SD) increment, 95% confidence interval (CI): 1.058 - 1.639, P = 0.014) and concentric LVH (OR = 1.545 per 1 SD increment, 95% CI: 1.173 - 2.035, P = 0.002) after fully adjusting for all confounding risk factors by multivariate logistic regression analyses. CONCLUSIONS: AIP was independently associated with an increased risk of LVH and concentric LVH in OSA patients. Therefore, AIP, as a practical and cost-effective test, might be useful in monitoring hypertrophic remodeling of the heart and improving CVDs risk stratification in clinical management of OSA.

Review on Microreactors for Photo-Electrocatalysis Artificial Photosynthesis Regeneration of Coenzymes.

In recent years, with the outbreak of the global energy crisis, renewable solar energy has become a focal point of research. However, the utilization efficiency of natural photosynthesis (NPS) is only about 1%. Inspired by NPS, artificial photosynthesis (APS) was developed and utilized in applications such as the regeneration of coenzymes. APS for coenzyme regeneration can overcome the problem of high energy consumption in comparison to electrocatalytic methods. Microreactors represent a promising technology. Compared with the conventional system, it has the advantages of a large specific surface area, the fast diffusion of small molecules, and high efficiency. Introducing microreactors can lead to more efficient, economical, and environmentally friendly coenzyme regeneration in artificial photosynthesis. This review begins with a brief introduction of APS and microreactors, and then summarizes research on traditional electrocatalytic coenzyme regeneration, as well as photocatalytic and photo-electrocatalysis coenzyme regeneration by APS, all based on microreactors, and compares them with the corresponding conventional system. Finally, it looks forward to the promising prospects of this technology.

Applications of Metals and Metal Compounds in Improving the Sensitivity of Microfluidic Biosensors - A Review.

The enhancement of detection sensitivity in microfluidic sensors has been a continuously explored field. Initially, many strategies for sensitivity improvement involved introducing enzyme cascade reactions, but enzyme-based reactions posed challenges in terms of cost, stability, and storage. Therefore, there is an urgent need to explore enzyme-free cascade amplification methods, which are crucial for expanding the application range and improving detection stability. Metal or metal compound nanomaterials have gained great attention in the exploitation of microfluidic sensors due to their ease of preparation, storage, and lower cost. The unique physical properties of metallic nanomaterials, including surface plasmon resonance, surface-enhanced Raman scattering, metal-enhanced fluorescence, and surface-enhanced infrared absorption, contribute significantly to enhancing detection capabilities. The metal-based catalytic nanomaterials, exemplified by Fe3O4 nanoparticles and metal-organic frameworks, are considered viable alternatives to biological enzymes due to their excellent performance. Herein, we provide a detailed overview of the applications of metals and metal compounds in improving the sensitivity of microfluidic biosensors. This review not only highlights the current developments but also critically analyzes the challenges encountered in this field. Furthermore, it outlines potential directions for future research, contributing to the ongoing development of microfluidic biosensors with improved detection sensitivity.

Efficacy of post-surgery family-based participatory cluster pain care in children with developmental dislocation of hip.

BACKGROUND: Developmental dislocation of the hip (DDH) is a common congenital deformity of the skeletal system in children. OBJECTIVE: To investigate the efficacy of post-surgery cluster nursing in children with DDH. METHODS: A total of 60 children with DDH who underwent hip joint orthopedic surgery in our hospital from September 2021 to September 2022 were enrolled as the research participants in this prospective study, and divided into the control group and the observation group according to the numerical table method, with 30 patients in each group. The control group was given routine pain care, and the observation group was given cluster pain care. The hip joint function scores, pain scores, self-rating anxiety score (SAS) were compared between the two groups and between before intervention and after intervention in the two groups. RESULTS: The pain score of the children and the SAS of the primary caregivers after the intervention in the observation group were lower than those in the control group (P< 0.05), and the hip joint function score and family satisfaction degree were higher than those in the control group (P< 0.05). CONCLUSION: Family-based cluster pain care can reduce pain in children with DDH after surgery, promote hip joint functional recovery, reduce the negative emotions of caregivers, and improve family satisfaction, and has clinical popularization value.

Cellulose de-polymerization is selective for bioethanol refinery and multi-functional biochar assembly using brittle stalk of corn mutant.

As lignocellulose recalcitrance principally restricts for a cost-effective conversion into biofuels and bioproducts, this study re-selected the brittle stalk of corn mutant by MuDR-transposon insertion, and detected much reduced cellulose polymerization and crystallinity. Using recyclable CaO chemical for biomass pretreatment, we determined a consistently enhanced enzymatic saccharification of pretreated corn brittle stalk for higher-yield bioethanol conversion. Furthermore, the enzyme-undigestible lignocellulose was treated with two-step thermal-chemical processes via FeCl2 catalysis and KOH activation to generate the biochar with significantly raised adsorption capacities with two industry dyes (methylene blue and Congo red). However, the desirable biochar was attained from one-step KOH treatment with the entire brittle stalk, which was characterized as the highly-porous nanocarbon that is of the largest specific surface area at 1697.34 m2/g and 2-fold higher dyes adsorption. Notably, this nanocarbon enabled to eliminate the most toxic compounds released from CaO pretreatment and enzymatic hydrolysis, and also showed much improved electrochemical performance with specific capacitance at 205 F/g. Hence, this work has raised a mechanism model to interpret how the recalcitrance-reduced lignocellulose is convertible for high-yield bioethanol and multiple-function biochar with high performance.

[Absorption of Ammonium by Three Substrates Materials in Constructed Wetland System].

The adsorption characteristics of ammonia nitrogen for constructed wetland were studied with ceramsite, quartz sand, and gravel. The material was characterized using scanning electron microscopy and a BET-specific surface area analyzer. It was found that the surface of ceramide was coarser than that of quartz sand and gravel, and the internal pores were more developed. The specific surface area of ceramide (18.97 m2·g-1) was higher than that of quartz sand and gravel. In the pure ammonia nitrogen solution and Grade I B standard for the wastewater treatment plant effluent ammonia nitrogen solution of the effluent from the simulated sewage plant, the adsorption capacity of the three substrates was as follows:ceramsite > gravel > quartz sand. The saturated adsorption capacity (63.55 m2·g-1) of ceramides was the highest in the mixed solution. The adsorption process of ammonia nitrogen by ceramides accorded with the pseudo-second-order kinetic model (R2 of 0.99 in the pure ammonia nitrogen solution and 0.98 in the mixed solution). The Freundlich and Langmuir models were used to fit the isothermal adsorption results in a pure ammonia nitrogen solution. It was found that the Freundlich model described the adsorption characteristics of the ceramics more accurately than the Langmuir model (R2=0.93), indicating that the adsorption of ammonia nitrogen by the ceramics was multilayer adsorption. In conclusion, the adsorption capacity of ceramide was strong, and the adsorption capacity of ceramide in the mixed solution was 31% higher than that in the pure ammonia nitrogen solution, which was suitable to be used as the matrix filler of constructed wetland.

Long noncoding RNA ZFAS1: A novel anti-apoptotic target in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial keratoplasty without efficacious drug treatment. Recent studies have emphasized the involvement of epigenetic regulation in FECD development. Long non-coding RNAs (lncRNAs) are recognized as crucial epigenetic regulators in diverse cellular processes and ocular diseases. In this study, we revealed the expression patterns of lncRNAs using high-throughput sequencing technology in FECD mouse model, and identified 979 significantly dysregulated lncRNAs. By comparing the data from FECD human cell model, we obtained a series of homologous lncRNAs with similar expression patterns, and revealed that these homologous lncRNAs were enriched in FECD related biological functions, with apoptosis (mmu04210) showing the highest enrichment score. In addition, we investigated the role of lncRNA zinc finger antisense 1 (ZFAS1) in apoptotic process. This study would broaden our understanding of epigenetic regulation in FECD development, and provide potential anti-apoptotic targets for FECD therapy.

Biomarkers of bipolar disorder based on metabolomics: A systematic review.

Bipolar disorder (BD) is a severe affective disorder characterized by recurrent episodes of depression or mania/hypomania, which significantly impair cognitive function, life skills, and social abilities of patients. There is little understanding of the neurobiological mechanisms of BD. The diagnosis of BD is primarily based on clinical assessment and psychiatric examination, highlighting the urgent need for objective markers to facilitate the diagnosis of BD. Metabolomics can be used as a diagnostic tool for disease identification and evaluation. This study summarized the altered metabolites in BD and analyzed aberrant metabolic pathways, which might contribute to the diagnosis of BD. Search of PubMed and Web of science for human BD studies related to metabolism to identify articles published up to November 19, 2022 yielded 987 articles. After screening and applying the inclusion and exclusion criteria, 16 untargeted and 11 targeted metabolomics studies were included. Pathway analysis of the potential differential biometabolic markers was performed using the Kyoto encyclopedia of genes and genomes (KEGG). There were 72 upregulated and 134 downregulated biomarkers in the untargeted metabolomics studies using blood samples. Untargeted metabolomics studies utilizing urine specimens revealed the presence of 78 upregulated and 54 downregulated metabolites. The targeted metabolomics studies revealed abnormalities in the metabolism of glutamate and tryptophan. Enrichment analysis revealed that the differential metabolic pathways were mainly involved in the metabolism of glucose, amino acid and fatty acid. These findings suggested that certain metabolic biomarkers or metabolic biomarker panels might serve as a reference for the diagnosis of BD.

Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy.

Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.

Single-cell RNA sequencing reveals the complex cellular niche of pterygium.

PURPOSE: Pterygium is a vision-threatening conjunctival fibrovascular degenerated disease with a high global prevalence up to 12 %, while no absolute pharmacotherapy has been applied in clinics. In virtue of single-cell RNA sequencing (scRNA-seq) technique, our study investigated underlying pathogeneses and potential therapeutic targets of pterygium from the cellular transcriptional level. METHODS: A total of 45605 cells from pterygium of patients and conjunctiva of normal controls (NC) were conducted with scRNA-seq, and then analyzed via integrated analysis, pathway enrichment, pseudotime trajectory, and cell-cell communications. Besides, immunofluorescence and western blot were performed in vivo and in vitro to verify our findings. RESULTS: In brief, 9 major cellular types were defined, according to canonical markers. Subsequently, we further determined the subgroups of each major cell lineages. Several newly identified cell sub-clusters could promote pterygium, including immuno-fibroblasts, epithelial mesenchymal transition (EMT)-epithelial cells, and activated vascular endothelial cells (activated-vEndo). Besides, we also probed the enrichment of immune cells in pterygium. Particularly, macrophages, recruited by ACKR1+activated-vEndo, might play an important role in the development of pterygium by promoting angiogenesis, immune suppression, and inflammation. CONCLUSION: An intricate cellular niche was revealed in pterygium via scRNA-seq analysis and the interactions between macrophages and ACKR1+ activated-vEndo might be the key part in the development of pterygia.

Responses of submerged macrophytes to different particle size microplastics and tetracycline co-pollutants at the community and population level.

Microplastics (MPs) and antibiotics are ubiquitous in aquatic ecosystems, and their accumulation and combined effects are considered emerging threats that may affect biodiversity and ecosystem function. The particle size of microplastics plays an important role in their combined effects with antibiotics. Submerged macrophytes are crucial in maintaining the health and stability of freshwater ecosystems. However, little is known about the combined effects of different particle size of MPs and antibiotics on freshwater plants, particularly their effects on submerged macrophyte communities. Thus, there is an urgent need to study their effects on the macrophyte communities to provide essential information for freshwater ecosystem management. In the present study, a mesocosm experiment was conducted to explore the effects of three particle sizes (5 µm, 50 µm, and 500 µm) of polystyrene-microplastics (PSMPs) (75 mg/L), tetracycline (TC) (50 mg/L), and their co-pollutants on interactions between Hydrilla verticillata and Elodea nuttallii. Our results showed that the effects of MPs are size-dependent on macrophytes at the community level rather than at the population level, and that small and medium sized MPs can promote the growth of the two test macrophytes at the community level. In addition, macrophytes at the community level have a stronger resistance to pollutant stress than those at the population level. Combined exposure to MPs and TC co-pollutants induces species-specific responses and antagonistic toxic effects on the physio-biochemical traits of submerged macrophytes. Our study provides evidence that MPs and co-pollutants not only affect the morphology and physiology at the population level but also the interactions between macrophytes. Thus, there are promising indications on the potential consequences of MPs and co-pollutants on macrophyte community structure, which suggests that future studies should focus on the effects of microplastics and their co-pollutants on aquatic macrophytes at the community level rather than only at the population level. This will improve our understanding of the profound effects of co-pollutants in aquatic environments on the structure and behavior of aquatic communities and ecosystems.

Development of the thermophilic fungus Myceliophthora thermophila into glucoamylase hyperproduction system via the metabolic engineering using improved AsCas12a variants.

BACKGROUND: Glucoamylase is an important enzyme for starch saccharification in the food and biofuel industries and mainly produced from mesophilic fungi such as Aspergillus and Rhizopus species. Enzymes produced from thermophilic fungi can save the fermentation energy and reduce costs as compared to the fermentation system using mesophiles. Thermophilic fungus Myceliophthora thermophila is industrially deployed fungus to produce enzymes and biobased chemicals from biomass during optimal growth at 45 °C. This study aimed to construct the M. thermophila platform for glucoamylase hyper-production by broadening genomic targeting range of the AsCas12a variants, identifying key candidate genes and strain engineering. RESULTS: In this study, to increase the genome targeting range, we upgraded the CRISPR-Cas12a-mediated technique by engineering two AsCas12a variants carrying the mutations S542R/K607R and S542R/K548V/N552R. Using the engineered AsCas12a variants, we deleted identified key factors involved in the glucoamylase expression and secretion in M. thermophila, including Mtstk-12, Mtap3m, Mtdsc-1 and Mtsah-2. Deletion of four targets led to more than 1.87- and 1.85-fold higher levels of secretion and glucoamylases activity compared to wild-type strain MtWT. Transcript level of the major amylolytic genes showed significantly increased in deletion mutants. The glucoamylase hyper-production strain MtGM12 was generated from our previously strain MtYM6 via genetically engineering these targets Mtstk-12, Mtap3m, Mtdsc-1 and Mtsah-2 and overexpressing Mtamy1 and Mtpga3. Total secreted protein and activities of amylolytic enzymes in the MtGM12 were about 35.6-fold and 51.9‒55.5-fold higher than in MtWT. Transcriptional profiling analyses revealed that the amylolytic gene expression levels were significantly up-regulated in the MtGM12 than in MtWT. More interestingly, the MtGM12 showed predominantly short and highly bulging hyphae with proliferation of rough ER and abundant mitochondria, secretion vesicles and vacuoles when culturing on starch. CONCLUSIONS: Our results showed that these AsCas12a variants worked well for gene deletions in M. thermophila. We successfully constructed the glucoamylase hyper-production strain of M. thermophila by the rational redesigning and engineering the transcriptional regulatory and secretion pathway. This targeted engineering strategy will be very helpful to improve industrial fungal strains and promote the morphology engineering for enhanced enzyme production.