Organic synthesis in the study of terpene-derived oxidation products in the atmosphere.

Covering: 1997 up to 2022Volatile biogenic terpenes involved in the formation of secondary organic aerosol (SOA) particles participate in rich atmospheric chemistry that impacts numerous aspects of the earth's complex climate system. Despite the importance of these species, understanding their fate in the atmosphere and determining their atmospherically-relevant properties has been limited by the availability of authentic standards and probe molecules. Advances in synthetic organic chemistry directly aimed at answering these questions have, however, led to exciting discoveries at the interface of chemistry and atmospheric science. Herein we provide a review of the literature regarding the synthesis of commercially unavailable authentic standards used to analyze the composition, properties, and mechanisms of SOA particles in the atmosphere.

Verifying AXL and putative proteins as SARS-CoV-2 receptors by DnaE intein-based rapid cell-cell fusion assay.

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.

Effects of treatment with Glucagon-like peptide-1 receptor agonist on prediabetes with overweight/obesity: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effects of Glucagon-like peptide-1 receptor agonist (GLP-1RA) on prediabetes with overweight/obesity. METHODS: A search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed to identify randomised controlled trials (up to 4 July 2022) which evaluated the effect of GLP-1RA on prediabetes with overweight/obesity. RESULTS: Eight hundred and nine articles were retrieved (80 from PubMed, 481 from Embase, 137 from Cochrane library, and 111 from Web of Science) and a total of 5 articles were included in this meta-analysis. More individuals in GLP-1RAs group regressed from prediabetes to normoglycemia than individuals in the placebo group (OR = 4.56, 95% CI:3.58, 5.80, P = 0.004); fewer individuals in GLP-1RAs group were diagnosed with diabetes than those in the placebo group (OR = 0.31, 95% CI:0.12,0.81, P = 0.017). Results from five studies showed that GLP-1RAs significantly reduced fasting glucose (mean difference = -0.41 mmol/L, 95% CI: -0.58, -0.25, P < 0.00001), with an acceptable heterogeneity (I2  = 42%). CONCLUSIONS: The present meta-analysis suggested that GLP-1RA significantly improves glucose metabolism, reduces systolic blood pressure and body weight in prediabetes with overweight/obesity. It could also prevent the development of diabetes and reverse abnormal glucose metabolism.

Distinct brain activity alterations of treatment for bipolar disorders with psychotherapy and drug therapy: activation likelihood estimation meta-analysis.

BACKGROUNDS: Many studies suggest that both psychotherapy and drug therapy are effective in the treatment of bipolar disorders (BDs). However, the pathophysiology of both types of intervention has not been established definitively. METHODS: An activation likelihood estimation meta-analysis was performed to identify the distinct brain activity alterations between psychotherapy and drug therapy for the treatment of BDs. Articles were identified by searching databases including PubMed, Embase, Cochrane Library, and Web of Science databases. Eligible studies on BDs were published up until 10 June 2021. RESULTS: 21 studies were included and we conducted a meta-analysis for different therapies and imaging tasks. After receiving psychotherapy, BD patients showed increased activation in the inferior frontal gyrus (IFG) and superior temporal gyrus. While after taking drug therapy, BD patients displayed increased activation in the anterior cingulate cortex, medial frontal gyrus, IFG, and decreased activation in the posterior cingulate cortex. The regions of brain activity changes caused by psychotherapy were mostly focused on the frontal areas, while drug therapy mainly impacted on the limbic areas. Different type of tasks also affected brain regions which were activated. CONCLUSIONS: Our comprehensive meta-analysis indicates that these two treatments might have effect on BD in their own therapeutic modes. Psychotherapy might have a top-down effect, while drug therapy might have a bottom-up effect. This study may contribute to differential diagnosis of BDs and would be helpful to finding more accurate neuroimaging biomarkers for BD treatment.

Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration.

BACKGROUND: Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn't been investigated in the pathogenesis of AMD. METHODS: Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-ß-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1α expression both in vitro and in vivo. RESULTS: In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO3 in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1α expression which mainly located in the nucleus. HIF1α translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO3. CONCLUSIONS: Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD. Video Abstract.

Effect of lipid oxidation on quality attributes and control technologies in dried aquatic animal products: a critical review.

Aquatic animals are viewed as a good source of healthy lipids. Although drying is an effective method for the preservation of aquatic animal products (AAPs), the whole process is accompanied by lipid oxidation. This article reviews the main mechanism of lipid oxidation in the drying process. It also summarizes the effects of lipid oxidation on the quality of dried aquatic animal products (DAAPs), including nutrients, color, flavor, and hazard components, especially for those harmful aldehydes and heterocyclic amines. In addition, it concluded that moderate lipid oxidation contributes to improving the quality of products. Still, excessive lipid oxidation produces hazardous substances and induces health risks. Hence, to obtain high-quality DAAPs, some effective control technologies to promote/prevent lipid oxidation are introduced and deeply discussed, including salting, high-pressure processing, irradiation, non-thermal plasma technology, defatting treatments, antioxidants, and edible coating. A systematic review of the effect of lipid oxidation on quality attributes and control technologies in DAAPs is presented, and some perspectives are made for future research.

The Effect of Behavior Couples Therapy on Alcohol and Drug Use Disorder: a Systematic Review and Meta-Analysis.

AIMS: Behavior couples therapy (BCT) is widely considered to be effective in the treatment of substance use disorders. However, the effect size of BCT in different outcome measures, and at different time points requires further study to prove it. METHODS: Systematic searches were performed in various databases. Ultimately, we identified 12 studies, involving 19 randomized controlled trials. We used Hedges' g as the effect size, and all pooled analyses were performed using random-effects models. RESULTS: After treatment, BCT was superior to control conditions (either an active or inactive control group) in frequency of substance use (g = 0.17), substance use consequences (g = -0.28) and relationship satisfaction (g = 0.45). After a 12-month follow-up, BCT remained superior to control conditions in frequency of substance use (g = 0.32), substance use consequences (g = -0.34) and relationship satisfaction (g = 0.31). In addition, BCT was more effective in reducing the frequency of substance use than individual-based treatment (IBT) (g = 0.23). There was no significant relationship between the effect size of BCT and publication year (t = 0.92, P = 0.372), percentage of females (t = -0.02, P = 0.987) or the number of treatment sessions (t = -0.52, P = 0.609). CONCLUSIONS: BCT was superior to the control conditions in all three outcome measures after treatment and at follow-up, and showed a relatively large effect size for relationship satisfaction. Moreover, BCT was superior to IBT in reducing the frequency of substance use.

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis.

PURPOSE: Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. METHODS: Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle-Ottawa scale was used to assess the quality of included studies. The Mantel-Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I2 statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. RESULTS: Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05-0.55; P = 0.02; I2 = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02-0.40; P = 0.03; I2 = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62-2.55; P = 0.52; I2 = 63%). CONCLUSION: Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.

Limonene anti-TMV activity and its mode of action.

The main component of orange peel essential oil is limonene. Limonene is a natural active monoterpene with multiple functions, such as antibacterial, antiseptic and antitumor activity, and has important development value in agriculture. This study found that limonene exhibited excellent anti-tobacco mosaic virus (TMV) bioactivity, with results showing that its protection activity, inactivation activity, and curative activity at 800 µg/mL were 84.93%, 59.28%, and 58.89%, respectively-significantly higher than those of chito-oligosaccharides. A direct effect of limonene on TMV particles was not observed, but limonene triggered the hypersensitive response (HR) in tobacco. Further determination of the induction activity of limonene against TMV demonstrated that it displayed good induction activity at 800 µg/mL, with a value of 60.59%. The results of physiological and biochemical experiments showed that at different treatment days, 800 µg/mL limonene induced the enhancement of defense enzymes activity in tobacco, including of SOD, CAT, POD, and PAL, which respectively increased by 3.2, 4.67, 4.12, and 2.33 times compared with the control (POD and SOD activities reached highest on the seventh day, and PAL and CAT activities reached highest on the fifth day). Limonene also enhanced the relative expression levels of pathogenesis related (PR) genes, including NPR1, PR1, and PR5, which were upregulated 3.84-fold, 1.86-fold and 1.71-fold, respectively. Limonene induced the accumulation of salicylic acid (SA), and increased the relative expression levels of genes related to SA biosynthesis (PAL) and reactive oxygen species (ROS) burst (RBOHB), which respectively increased by 2.76 times and 4.23 times higher than the control. Systemic acquired resistance (SAR) is an important plant immune defense against pathogen infection. The observed accumulation of SA, the enhancement of defense enzymes activity and the high-level expression of defense-related genes suggested that limonene may induce resistance to TMV in tobacco by activating SAR mediated by the SA signaling pathway. Furthermore, the experimental results demonstrated that the expression level of the chlorophyll biosynthesis gene POR1 was increased 1.72-fold compared to the control in tobacco treated with 800 µg/mL limonene, indicating that limonene treatment may increase chlorophyll content in tobacco. The results of pot experiment showed that 800 µg/mL limonene induced plant resistance against Sclerotinia sclerotiorum (33.33%), Phytophthora capsici (54.55%), Botrytis cinerea (50.00%). The bioassay results indicated that limonene provided broad-spectrum and long-lasting resistance to pathogen infection. Therefore, limonene has good development and utilization value, and is expected to be developed into a new botanical-derived anti-virus agent and plant immunity activator in addition to insecticides and fungicides.

A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of head and neck, which seriously threatens human life and health. However, the mechanism of hypoxia-associated genes (HAGs) in HNSCC remains unelucidated. This study aims to establish a hypoxia-associated gene signature and the nomogram for predicting the prognosis of patients with HNSCC. METHODS: Previous literature reports provided a list of HAGs. The TCGA database provided genetic and clinical information on HNSCC patients. First, a hypoxia-associated gene risk model was constructed for predicting overall survival (OS) in HNSCC patients and externally validated in four GEO datasets (GSE27020, GSE41613, GSE42743, and GSE117973). Then, immune status and metabolic pathways were analyzed. A nomogram was constructed and assessed the predictive value. Finally, experimental validation of the core genes was performed by qRT-PCR. RESULTS: A HNSCC prognostic model was constructed based on 8 HAGs. This risk model was validated in four external datasets and exhibited high predictive value in various clinical subgroups. Significant differences in immune cell infiltration levels and metabolic pathways were found between high and low risk subgroups. The nomogram was highly accurate for predicting OS in HNSCC patients. CONCLUSIONS: The 8 hypoxia-associated gene signature can serve as novel independent prognostic indicators in HNSCC patients. The nomogram combining the risk score and clinical stage enhanced predictive performance in predicting OS compared to the risk model and clinical characteristics alone.

Coexpression network analysis identified MT3 as a hub gene that promotes the chemoresistance of oral cancer by regulating the expression of YAP1.

BACKGROUND: Oral cancer is considered one of the most malignant types of tumors and is known for its high likelihood of recurrence and metastasis. During clinical treatment, patients with oral cancer often develop resistance to chemotherapy, making the treatment process challenging. The purpose of this study was to investigate the genes related to chemotherapy resistance and their mechanisms in oral cancer patients. METHODS: The "limma" package was used to identify the differentially expressed genes between tumor and normal tissues from TCGA dataset. Subsequently, the "WGCNA" package was utilized to discover genes associated with chemoresistance. Cisplatin-resistant oral cancer cell lines were obtained through exposure to gradually increasing doses of cisplatin. SiRNA was used to knock down the MT3 and YAP1 genes to validate their functions. Finally, the therapeutic efficacy of combining a YAP1 inhibitor with cisplatin was confirmed by inoculating an oral cancer cell line in mice. RESULTS: In our study, we analyzed 43 OSCC samples and identified 724 different genes using the weighted gene coexpression network analysis (WGCNA) method. Among these genes, MT3 stood out as strongly associated with chemotherapy resistance. Patients with high MT3 expression had worse prognoses, and MT3 levels were elevated in drug-resistant patients. Knocking down MT3 reversed tumor cell chemoresistance. We also observed that MT3 increased the expression of YAP1, potentially contributing to chemotherapy resistance by inducing tumor stemness through YAP1. In animal models, using YAP1 inhibitors improved the effectiveness of cisplatin in treating chemoresistant oral cancer. CONCLUSIONS: MT3 is related to chemotherapy resistance, which may be caused by its promotion of YAP1 expression and induction of tumor cell stemness. Inhibiting the activity of MT3 and YAP1 is helpful for increasing chemotherapy sensitivity.

[Research progress in pharmacotherapy of insomnia].

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.

TCF7L2 promotes ER stress signaling in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common blindness in working-age adults. Transcription factor 7 like 2 (TCF7L2) is a susceptibility gene of DR, however, its roles in the pathogenesis of DR are still largely unknown. In this study, we found that TCF7L2 was mainly located in the cell nucleus of retinal ganglion cell layer (GCL) and inner nuclear layer (INL), while it was not expressed in the cell nucleus of retinal outer nuclear layer (ONL). Expression of TCF7L2 was significantly elevated in the retinas of db/db diabetic mice and oxygen-induced retinopathy (OIR) mice. Also, in Ad-hTCF7L2 treated hiPSCs-derived retinal progenitor cells (RPCs), activating transcription factor 6 (ATF6)-related endoplasmic reticulum (ER) stress signaling was remarkably activated. Moreover, knockdown of TCF7L2 significantly inhibited ATF6-related ER stress signaling. Furthermore, the data of endothelial permeability assay showed that RPCs pretreated with Ad-hTCF7L2 lead to enhanced monolayer permeability of human umbilical vein endothelial cells (HUVECs), and knockdown of TCF7L2 or ATF6 in RPCs could alleviate the monolayer permeability of HUVECs. Thus, our results showed that TCF7L2 could trigger ATF6-related ER stress signaling and promote vein endothelial cell permeability, which will provide important insight into the role of TCF7L2 in the pathogenesis of DR and contribute to designing potential therapies.

Synthesis of Berberine and Canagliflozin Chimera and Investigation into New Antibacterial Activity and Mechanisms.

Berberine is an isoquinoline alkaloid isolated from Chinese herbal medicines such as Coptis chinensis. It has many pharmacological actions, such as antibacterial, hypoglycemic, anti-inflammatory, and so on. However, due to the low lipophilicity of berberine, it is difficult to penetrate the bacterial cell membrane and also difficult to be absorbed orally and usually needs a relatively high dose to achieve the ideal effect. The purpose of this study is to transform the structure of berberine in order to improve the bioavailability of berberine and reduce the dosage. Moreover, we introduce a pharmacophore named Canagliflozin, a hypoglycemic drug (which was also found to have potential anti-bacterial activity) into BBR to see whether this new compound has more existed activities. We at first connected berberine with Canagliflozin, to form a new compound (BC) and see whether BC has synergic effects. We use microbroth dilution method to determine the minimum inhibitory concentration of BC, determine the bacterial growth with the enzyme labeling instrument, observe the formation of bacterial biofilm with crystal violet staining method, observe the bacterial morphology with field emission scanning electron microscope, and determine the intracellular protein with SDS-PAGE. The above indicators reflect the damage of BC to bacteria. New compound BC was successfully obtained by chemical synthesis. The minimal inhibitory concentration of compound BC on three bacteria was significantly better than that of berberine and canagliflozin alone and the combination of berberine and canagliflozin. Moreover, compound BC has obvious destructive effect on bacterial morphology and biofilm, and the compound also has destructive effect on intracellular proteins. Therefore, new compound BC has broad-spectrum antibacterial activity and the inhibitory effect of BC might play a role by destroying the integrity of biofilm and the intracellular protein of bacteria. In conclusion, we create a new molecular entity of berberine and Canagliflozin chimera and open up a new prospect for berberine derivatives in the treatment of bacterial infection.

Determinants of macular ganglion cell-inner plexiform layer thickness in normal Chinese adults.

BACKGROUND: Demographic, systemic and ocular factors may impact macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements. This study aimed to investigate the influences of multiple potential determinants of macular GCIPL thickness in normal Chinese adults. METHODS: This was a retrospective study conducted on 225 normal eyes from 225 healthy Chinese adults. GCIPL thickness were obtained using Cirrus high-definition optical coherence tomography (OCT). The age, gender, laterality, spherical equivalent (SE) refractive error, intraocular pressure (IOP), axial length (AL), central cornea thickness (CCT), circumpapillary retinal nerve fibre layer (pRNFL) thickness and OCT signal strength were recorded and their respective effect on GCIPL thickness parameters were evaluated. RESULTS: The mean (± SD) average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness was 84.56 ± 5.36, 81.32 ± 5.58, 83.08 ± 5.37, 85.70 ± 5.95, 87.15 ± 6.26, 85.07 ± 6.11, 82.46 ± 5.76, and 83.88 ± 5.59 µm, respectively. Determinants of thinner GCIPL thickness were older age (P = 0.001-0.117; effects enhanced if age over 40 years), thinner pRNFL (all P < 0.001), and weaker signal strength (all P < 0.001). No significant difference was found between males and females (P = 0.069-0.842), and between right eyes and the left eyes (P = 0.160-0.875) except that of superonasal GCIPL thickness (P < 0.001). There was no significant correlation between GCIPL thickness and SE, IOP, CCT, and AL (P = 0.135-0.968). CONCLUSIONS: Individual determinants associated with thinner GCIPL thickness were older age (particularly over 40 years of age), thinner pRNFL, and weaker OCT signal strength. This is relevant in comprehensively understanding the normative data and differentiating normal aging from abnormalities.

Canagliflozin Modulates Hypoxia-Induced Metastasis, Angiogenesis and Glycolysis by Decreasing HIF-1α Protein Synthesis via AKT/mTOR Pathway.

The microenvironment plays a vital role in tumor progression, and hypoxia is a typical microenvironment feature in nearly all solid tumors. In this study, we focused on elucidating the effect of canagliflozin (CANA), a new class of antidiabetic agents, on hepatocarcinoma (HCC) tumorigenesis under hypoxia, and demonstrated that CANA could significantly inhibit hypoxia-induced metastasis, angiogenesis, and metabolic reprogramming in HCC. At the molecular level, this was accompanied by a reduction in VEGF expression level, as well as a reduction in the epithelial-to-mesenchymal transition (EMT)-related proteins and glycolysis-related proteins. Next, we focused our study particularly on the modulation of HIF-1α by CANA, which revealed that CANA decreased HIF-1α protein level by inhibiting its synthesis without affecting its proteasomal degradation. Furthermore, the AKT/mTOR pathway, which plays an important role in HIF-1α transcription and translation, was also inhibited by CANA. Thus, it can be concluded that CANA decreased metastasis, angiogenesis, and metabolic reprogramming in HCC by inhibiting HIF-1α protein accumulation, probably by targeting the AKT/mTOR pathway. Based on our results, we propose that CANA should be evaluated as a new treatment modality for liver cancer.

Evaluation of the genetic association between early-onset primary angle-closure glaucoma and retinitis pigmentosa.

Primary angle-closure glaucoma (PACG) and retinitis pigmentosa (RP) can co-occur, but the mechanism of their association is not yet established. The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP, and to determine the association between PACG and RP. Patients with early-onset PACG (age of onset <45 years) with or without RP were selected from the glaucoma outpatient department after full ocular examinations by the same glaucoma specialist (LX). Ocular biometry parameters were statistically analyzed. Blood samples were collected from the probands, and genomic DNA was sent out for whole exome sequencing. Variants in 326 selected genes, were extracted from the whole exome sequencing data and filtered using multiple bioinformatics analysis. The 326 genes included 10 PACG-associated genes from two genome wide association studies; 45 genes associated with anterior segment dysgenesis, microcornea, and microphthalmia; and 271 RetNet genes. Potential pathogenic variants (PPV) were obtained and underwent further genotype-phenotype analysis. As a result, a total of 32 probands with early-onset PACG were collected; nine had accompanying RP. No significant differences were noted for ocular biometry parameters between patients with PACG with RP and with PACG alone. Systematic analysis of the variants revealed that 16 of 32 probands (50%) carried PPV in 15 of 326 genes, including 14 RetNet genes and one anterior segment dysgenesis-associated gene. Of these 16 probands with PPV, five (55.56%) were from the group of nine probands with both had PACG and RP and 11 (47.83%) were from the group of 23 probands with PACG alone. Of the 15 genes, five genes, CRB1, COL2A1, RHO, RP1L1, and PAX6, were reported to cause phenotypes including glaucoma. The variants in RetNet genes appeared to be associated with a significant proportion of PACG, especially in probands with both PACG and RP. These findings enrich the phenotype spectrum of RetNet genes and provide clues for genetic screening for glaucoma. Our study suggests a genetic association between PACG and RP, although the cause-effect relationship between them needs further validation.

Comprehensive genetic analysis uncovers the mutational spectrum of MFRP and its genotype-phenotype correlation in a large cohort of Chinese microphthalmia patients.

PURPOSE: Microphthalmia is a severe congenital ocular disease featured by abnormal ocular development. The aim of this study was to detail the genetic and clinical characteristics of a large cohort of Chinese patients with microphthalmia related to MFRP variants, focusing on uncovering genotype-phenotype correlations. METHODS: Fifty microphthalmia patients from 44 unrelated Chinese families were recruited. Whole-exome sequencing (WES) was conducted to analyze the coding regions and adjacent intronic regions of MFRP. Axial lengths (AL) were measured for all probands and available family members. Protein structures of mutations with high frequency in our cohort were predicted. The genotype-phenotype correlations were explored by statistical analysis. RESULTS: Sixteen MFRP variants were detected in 17 families, accounting for 38.64 % of all microphthalmia families. There were 9 novel mutations (c.427+1G>C, c.428-2A>C, c.561_575del:p.A188_E192del, c.836G>A:p.C279Y, c.1010_1021del:p.H337_E340del:p.Y479*, c.1516_1517del:p.S506Pfs*66, c.1561T>G:p.C521G, c.1616G>A:p.R539H, and c.1735C>T:p.P579S) and six previously reported variants in MFRP, with p.E496K and p.H337_E340del being highly frequent, found in eight (47.06 %) and two families (11.76 %), respectively. Seven variants (43.75 %) were located in the C-terminal cysteine-rich frizzled-related domain (CRD) (7/16, 43.75 %). Protein prediction implicated p.E496K and p.H337_E340del mutations might lead to a destabilization of the MFRP protein. The average AL of all 42 eyes was 16.02 ± 1.05 mm, and 78.36 % of eyes with AL < 16 mm harbored p.E496K variant. Twenty-six eyes with variant variant had shorter AL than that of the other 16 eyes without this variant (p = 0.006), highlighting a novel genotype-phenotype correlation. CONCLUSIONS: In this largest cohort of Chinese patients with microphthalmia, the 9 novel variants, high frequency of p.E496W, and mutation hotspots in CRD reveals unique insights into the MFRP mutation spectrum among Chinese patients, indicating ethnic variability. A new genotype-phenotype correlation that p.E496K variant associated with a shorter AL is unveiled. Our findings enhance the current knowledge of MFRP-associated microphthalmia and provide valuable information for prenatal diagnosis as well as future therapy.

Expression characteristics of lipid metabolism-related genes and correlative immune infiltration landscape in acute myocardial infarction.

Lipid metabolism is an important part of the heart's energy supply. The expression pattern and molecular mechanism of lipid metabolism-related genes (LMRGs) in acute myocardial infarction (AMI) are still unclear, and the link between lipid metabolism and immunity is far from being elucidated. In this study, 23 Common differentially expressed LMRGs were discovered in the AMI-related mRNA microarray datasets GSE61144 and GSE60993. These genes were mainly related to "leukotriene production involved in inflammatory response", "lipoxygenase pathway", "metabolic pathways", and "regulation of lipolysis in adipocytes" pathways. 12 LMRGs (ACSL1, ADCY4, ALOX5, ALOX5AP, CCL5, CEBPB, CEBPD, CREB5, GAB2, PISD, RARRES3, and ZNF467) were significantly differentially expressed in the validation dataset GSE62646 with their AUC > 0.7 except for ALOX5AP (AUC = 0.699). Immune infiltration analysis and Pearson correlation analysis explored the immune characteristics of AMI, as well as the relationship between these identified LMRGs and immune response. Lastly, the up-regulation of ACSL1, ALOX5AP, CEBPB, and GAB2 was confirmed in the mouse AMI model. Taken together, LMRGs ACSL1, ALOX5AP, CEBPB, and GAB2 are significantly upregulated in AMI patients' blood, peripheral blood of AMI mice, myocardial tissue of AMI mice, and therefore might be new potential biomarkers for AMI.