Liposomes in the cosmetics: present and outlook.

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation.

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling.

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.

The landscape of allelic expression and DNA methylation at the bovine SGCE/PEG10 locus.

Genomic imprinting is an epigenetic regulation in mammals in which a small subset of genes is monoallelically expressed dependent on their parental origin. A large imprinted domain, SGCE/PEG10 locus, is located on human chromosome 7q21s and mouse proximal chromosome 6. However, genomic imprinting of bovine SGCE/PEG10 cluster has not been systematically studied. In this study, we investigated allele expression of 14 genes of the SGCE/PEG10 locus in bovine somatic tissues and term placenta using a single nucleotide polymorphism (SNP)-based sequencing method. In addition to SGCE and PEG10, two conserved paternally expressed genes in human and mice, five other genes (TFPI2, GNG11, ASB4, PON1, and PON3) were paternally expressed. Three genes, BET1, COL1A2, and CASD1, exhibited tissue-specific monoallelic expression. CALCR showed monoallelic expression in tissues but biallelic expression in the placenta. Three genes, GNGT1, PPP1R9A, and PON2, showed biallelic expression in cattle. Five differentially methylated regions (DMRs) were found to be associated with the allelic expression of TFPI2, COL1A2, SGCE/PEG10, PON3, and ASB4 genes, respectively. The SGCE/PEG10 DMR is a maternally hypermethylated germline DMR, but TFPI2, COL1A2, PON3, and ASB4 DMRs are secondary DMRs. In summary, we identified five novel bovine imprinted genes (GNG11, BET1, COL1A2, CASD1, and PON1) and four secondary DMRs at the SGCE/PEG10 locus.

CT Quantification of Interstitial Lung Abnormalities and Changes of Agerelated Pathomorphology.

BACKGROUND: Interstitial lung abnormalities (ILA) are associated with further disease progression, increased mortality risk, and decline in lung function in the elderly, which deserves enough attention. OBJECTIVE: The objective of this study was to quantify the extent of interstitial lung abnormalities (ILA) in a non-smoking asymptomatic urban cohort in China using low-dose CT (LDCT) and to analyze the age-related pathological changes. METHODS: We retrospectively analyzed clinical data and chest LDCT images from a cohort of 733 subjects who were categorized into 3 groups: 18-39, 40-59, and ≥60 years old according to age. Furthermore, we selected 40 cases of wax-embedded lung tissue blocks archived after pulmonary bullectomy and the same age groups were categorized. Four representative CT signs of ILA, including interlobular septal thickening (ILST), intralobular interstitial thickening (ILIT), ground-glass opacity (GGO), and reticular shadow (RS), were semi-quantified based on the percentage of the affected area. The scores and distribution of four CT signs of ILA were compared between different sex and age groups. The age-related pathological changes were analyzed. RESULTS: The ILA findings were found predominantly in the lower lobes and the subpleural region. The semi-quantitative scores of four CT signs in all subjects under 40 were 0. However, in subjects over 40 years old, the scores gradually increased with age, although most of them remained low. The size of the alveoli increased, the number of alveoli decreased, the alveolar septum became thinner, and the number of ATII cells increased with age. A statistically significant difference was observed among the different age groups (χ2=50.624, P=0.033; χ2=80.000, P=0.043; χ2=33.833, P=0.000; χ2=13.525, P=0.031). The macrophage population and the percentage of collagen fibers in the alveolar septum increased, while the percentage of elastic fibers decreased with age. There was no significant difference among the different age groups (χ2=19.817, P=0.506; χ2=52.419, P=0. 682; χ2=54.868, P=0.518). CONCLUSION: When the four CT signs mentioned above are in the upper central area, and the score has a medium or high score, it is crucial to determine the underlying pathological causes. ILA may be the result of chronic lung injury.

A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1.

Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18.

A matched case-control study of early cervical spondylotic myelopathy based on diffusion magnetic resonance imaging.

BACKGROUND: Early cervical spondylotic myelopathy (CSM) is challenging to diagnose and easily missed. Diffusion MRI (dMRI) has the potential to identify early CSM. METHODS: Using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI), a 1:1 matched case-control study was conducted to evaluate the potential of dMRI in identifying early CSM and assessing uncompressed segments of CSM patients. CSM patients and volunteers were matched by age and spinal location. The differences in dMRI parameters between groups were assessed by the paired t-test, the multicollinearity of the dMRI parameters was evaluated by the variance inflation factor (VIF), and the value of dMRI parameters in distinguishing controls from CSM patients was determined by logistic regression. The univariate t-test was used to analyse differences between CSM patients and volunteers in adjacent uncompressed areas. RESULTS: In total, 56 CSM patients and 56 control volunteers were included. Paired t-tests revealed significant differences in nine dMRI parameters between groups. Multicollinearity calculated through VIF and combined with logistic regression showed that the orientation division index (ODI) was significantly positively correlated (r = 2.12, p = 0.035), and the anisotropic water fraction (AWF) was significantly negatively correlated (r = -0.98, p = 0.015). The fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (ISOVF), ODI, and AWF were significantly different in the upper and lower uncompressed areas at all ages. CONCLUSION: dMRI can noninvasively identify early CSM patients and potentially identify the extent of CSM lesions involving the cervical spinal cord. CRITICAL RELEVANCE STATEMENT: Diffusion MRI (dMRI) can identify early cervical spondylotic myelopathy (CSM) and has the potential to help determine the extent of CSM involvement. The application of dMRI can help screen for early CSM and develop clinical surgical and rehabilitation treatment plans. KEY POINTS: • Diffusion MRI can differentiate between normal and early-stage cervical spondylotic myelopathy patients. • Diffusion MRI has the ability to identify the extent of spinal cord involvement in cervical spondylotic myelopathy. • Diffusion MRI enables the early screening of cervical spondylotic myelopathy and helps guide clinical treatment.

Urine albumin-to-creatinine ratio diurnal variation rate predicts outcomes in idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN. METHODS: Patients' baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone. RESULTS: The formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = - 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone. CONCLUSION: UACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment.

Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway.

The key circadian genes, Period1(Per1), Period2(Per2), and Period3(Per3), constitute the mammalian Period gene family. The abnormal expression of Per1 and Per2 is closely related to tumor development, but there are few reports on Per3 and tumorigenesis. This study was conducted to determine whether the abnormal expression of Per3 could influence the progression of astroblastoma. The results indicated that the expression level of Per3 was increased in astroblastoma cells, and the high expression of Per3 was correlated with the poor overall survival time of glioma patients. The role of Per3 in astroblastoma cells was then investigated using two approaches: interference and overexpression. The interference of Per3 inhibited astroblastoma cell proliferation by inducing the cell cycle at the S phase. The interference of Per3 inhibited the migration and invasion of astroblastoma cells, while promoted the astroblastoma cell apoptosis and the expression of the apoptosis genes Cleaved-CASP3, P53, and BAX. The overexpression of Per3 promoted proliferation by affecting the S phase distribution of the astroblastoma cell cycle. The overexpression of Per3 promoted the migration and invasion of astroblastoma cells, while inhibited the astroblastoma cell apoptosis and the expression of apoptosis genes Cleaved-CASP3, P53, and BAX. RNA-seq analysis showed that the interference of Per3 in astrocytoma cells resulted in significant changes in the expression levels of 764 genes. Among the differentially expressed genes enriched in apoptosis-related pathways, the interference of Per3 resulted in significant upregulation of MARCKSL1 expression, in contrast to significant downregulation of SFRP4, EPB41L3, and GPC5 expression. Taken together, our results suggest that Per3 appears to be a pro-cancer gene by altering the proliferation, migration, invasion, and apoptosis of astroblastoma cells. As a result, the Per3 gene may be a promising therapeutic target in the treatment of astroblastoma.

Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Autophagy inhibition mediated by trillin promotes apoptosis in hepatocellular carcinoma cells via activation of mTOR/STAT3 signaling.

Apoptosis and autophagy have been shown to act cooperatively and antagonistically in self-elimination process. On the one side, apoptosis and autophagy can act as partners to induce cell death in a coordinated or cooperative manner; on the flip side, autophagy acts as an antagonist to block apoptotic cell death by promoting cell survival. Our previous research indicated that trillin could induce apoptosis of PLC/PRF/5 cells, but the effects of trillin on autophagy as well as its functional relationship to apoptosis have not been elucidated. Here, the running study aims to investigate the function and molecular mechanism of trillin on autophagy with hepatocellular carcinoma (HCC) cells. The objective of this study is to investigate the molecular mechanism of trillin on autophagy in HCC cells. Protein levels of autophagy markers beclin1, LC3B, and p62 were detected by western blotting. 6-Hydroxyflavone and stattic were used to test the role of trillin regulation of autophagy via serine threonine kinase (AKT)/extracellular-regulated protein kinases (ERK) 1/2/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Flow cytometry was used to detect caspase 3 activity and apoptosis in PLC/PRF/5 cells treated with trillin for 24 h with or without rapamycin, stattic, and 6-hydroxyflavone. The protein level of autophagy marker beclin1 was decreased, whilst the protein level of p62 was significantly increased by trillin treatment, indicating trillin treatment led to inhibition of autophagy in HCC cells. Trillin treatment could reduce the protein levels of p-AKT and p-ERK1/2, but enhance the protein levels of mTOR and p-mTOR, suggesting that trillin could inhibit AKT/ERK rather than mTOR. The AKT/ERK activator 6-hydroxyflavone could reverse the loss of AKT and ERK1/2 phosphorylation induced by trillin, implying that trillin impairs autophagy through activated mTOR rather than AKT/ERK. STAT3 and p-STAT3 were significantly upregulated by the trillin treatment with an increase in dose from 0 to 50 µM, suggesting that autophagy inhibition is mediated by trillin via activation of STAT3 signaling. The STAT3 inhibitor stattic significantly reversed the increased STAT3 phosphorylation at tyrosine 705 induced by trillin. The mTOR signaling inhibitor rapamycin reversed the trillin-induced mTOR phosphorylation enhancement but exerted no effects on total mTOR levels, suggesting trillin treatment led to inhibition of autophagy in HCC cells through activating mTOR/STAT3 pathway. Furthermore, caspase 3 activities and the total rate of apoptosis were increased by trillin treatment, which was reversed by rapamycin, stattic, and 6-hydroxyflavone, proving that trillin promotes apoptosis via activation of mTOR/STAT3 signaling. Trillin induced autophagy inhibition and promoted apoptosis in PLC/PRF/5 cells via the activation of mTOR/STAT3 signaling. Trillin has the potential to be a viable therapeutic option for HCC treatment.

Enhanced fungicidal efficacy and improved interfacial properties with the co-delivery of prothioconazole and tebuconazole using polylactic acid microspheres.

BACKGROUND: Prothioconazole (PTC) is one of the leading fungicide products worldwide. However, excessive use of PTC facilitates the development of resistance. Pesticide compounding technology plays an important role in reducing pesticide resistance. Microspherization technology for the construction of pesticide dual-loaded systems has recently provided a new direction for researching novel and efficient pesticide formulations. In this study, prothioconazole-tebuconazole@polylactic acid microspheres (PTC-TBA@PLA MS) were constructed by combining these two technologies. RESULTS: The final PTC-TBA@PLA MS were selected by an orthogonal method, which were uniformly spherical with smooth surface. The resultant drug loading (DL) and average particle size of PTC-TBA@PLA MS were 31.34% and 22.3 µm, respectively. A PTC-TBA@PLA MS suspending agent (SC) with a high suspension rate of 94.3% was prepared according to the suspension rate, dumping ability and stability. Compared with a commercial SC, the PTC-TBA@PLA MS SC had a larger cumulative release and better interfacial properties. Biological experiments showed that PTC-TBA@PLA MS SC had an obviously improved bactericidal effect than the commercial SC. CONCLUSION: The constructed PTC-TBA@PLA MS system detailed here is expected to reduce the risk of resistance and the frequency of pesticide use while enhancing fungal control. © 2023 Society of Chemical Industry.

Adipogenic and osteogenic effects of OBS and synergistic action with PFOS via PPARγ-RXRα heterodimers.

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1-100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures.

Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma.

CONTEXT: Papillary thyroid microcarcinoma (PTMC) is the most common type of thyroid cancer. It has been shown that lymph node metastasis is associated with poor prognosis in patients with PTMC. OBJECTIVE: We aim to characterize the PTMC transcriptome landscape and identify the candidate transcripts that are associated with lateral neck lymph node metastasis of PTMC. METHODS: We performed full-length transcriptome sequencing in 64 PTMC samples. Standard bioinformatic pipelines were applied to characterize and annotate the full-length expression profiles of 2 PTMC subtypes. Functional open reading frame (ORF) annotation of the known and novel transcripts were predicted by HMMER, DeepLoc, and DeepTMHMM tools. Candidate transcripts associated with the pN1b subtype were identified after transcript quantification and differential gene expression analyses. RESULTS: We found that skipping exons accounted for the more than 27.82% of the alternative splicing events. At least 42.56% of the discovered transcripts were novel isoforms of annotated genes. A total of 39 193 ORFs in novel transcripts and 18 596 ORFs in known transcripts were identified. Distribution patterns of the characterized transcripts in functional domain, subcellular localization, and transmembrane structure were predicted. In total, 1033 and 1204 differentially expressed genes were identified in the pN0 and pN1b groups, respectively. Moreover, novel isoforms of FRMD3, NOD1, and SHROOM4 were highlighted for their association with pN1b subtype. CONCLUSION: Our data provided the global transcriptome landscape of PTMC and also revealed the novel isoforms that associated with PTMC aggressiveness.

Controlled Construction of Core-Shell Structured Prussian Blue Analogues towards Enhanced Oxygen Reduction.

Metal-organic frameworks-based electrocatalysts have been developed as highly desirable and promising candidates for catalyzing oxygen reduction reaction (ORR), which, however, usually need to be prepared at elevated temperatures and may suffer from the framework collapse in water environments, largely preventing its industrial application. Herein, this work demonstrates a facile low-temperature ion exchange method to synthesize Mn and Fe co-loaded Prussian blue analogues possessing core-shell structured frameworks and favorable water-tolerance. Among the catalysts prepared, the optimal HMPB-2.6Mn shows a high ORR electrocatalytic performance featuring a half-wave potential of 0.86 V and zinc-air battery power density of 119 mW cm-2 , as well as negligible degradation up to 60 h, which are comparable to commercial Pt/C. Such an excellent electrocatalytic performance is attributed to the special core-shell-like structure with Mn concentrated in outer shell, and the synergetic interactions between Mn and Fe, endowing HMPB-Mn with outstanding ORR activity and good stability.

Epidemiology of respiratory pathogens in patients with acute respiratory tract infection in Xiamen, China: A retrospective survey from 2020 to 2022.

Acute respiratory tract infections (ARTI) are caused by respiratory pathogens and range from asymptomatic infections to severe respiratory diseases. These diseases can be life threatening with high morbidity and mortality worldwide. Under the pandemic of coronavirus disease 2019 (COVID-19), little has been reported about the pathogen etiologies and epidemiology of patients suffering from ARTI of all age in Xiamen. Region-specific surveillance in individuals with ARTI of all ages was performed in Xiamen from January 2020 to October 2022. Here, we observed the epidemiological characteristics of thirteen pathogens within ARTI patients and further revealed the difference of that between upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In total 56.36 % (2358/4184) of the ARTI patients were positive for at least one respiratory pathogen. Rhinovirus (RVs, 29.22 %), influenza A (FluA, 19.59 %), respiratory syncytial virus (RSV, 18.36 %), metapneumovirus (MPV, 13.91 %), and adenovirus (ADV, 10.31 %) were the five leading respiratory pathogens. Respiratory pathogens displayed age- and season-specific patterns, even between URTI and LRTI. Compared with other groups, a higher proportion of FluA (52.17 % and 68.75 %, respectively) infection was found in the adult group and the elder group, while the lower proportion of RVs (14.11 % and 11.11 %) infection was also observed in them. Although ARTI cases circulated throughout the year, RVs, FluB, and BoV peaked in autumn, and FluA circulated more in summer. Besides, the co-infectious rate was 8.7 % with the most common for RVs. Logistic regression analyses revealed the correlations between respiratory pathogens and disease types. These results are essential for replenishing epidemiological characteristics of common respiratory pathogens that caused ARTI in Xiamen during the epidemic of COVID-19, and a better understanding of it might optimize the local prevention and clinical control.

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study.

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

SPOP regulates the expression profiles and alternative splicing events in human hepatocytes.

Speckle type BTB/POZ protein (SPOP) may have cancer promoting or inhibiting effects. At present, the role of SPOP in hepatocellular carcinoma (HCC) has rarely been studied. In this study, to investigate the effects of SPOP in HCC and elucidate the underlying molecular mechanisms of its relationship with genes, differentially expressed genes (DEGs) were classified through RNA sequencing. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional pathway analysis were used to further predict the function of DEGs after the overexpression of SPOP. The biological function of SPOP-regulated alternative splicing events in cells is comprehensively assessed. The Cancer Genome Atlas database and Gene Expression Omnibus dataset were performed to evaluate the correlation between SPOP and HCC progression. Due to SPOP overexpression, 56 DEGs in the HCC related pathway were further identified. The results showed that SPOP overexpression facilitated the cell proliferation and changed the gene expression profiles of human normal hepatocytes. SPOP-regulated alternative splicing events were involved in pathways associated with cellular processes, metabolism, environmental information procession, organismal systems, and so on. In conclusion, SPOP may potentially exhibit tumor-promoting effects, necessitating further investigations to unveil its molecular mechanisms comprehensively.

Paeonol ameliorates hippocampal neuronal damage by inhibiting GRM5/GABBR2/ß-arrestin2 and activating the cAMP-PKA signaling pathway in premenstrual irritability rats.

Premenstrual dysphoric disorder (PMDD) is a periodic psychiatric disorder with high prevalence in women of childbearing age, seriously affecting patients' work and life. Currently, the international first-line drugs for PMDD have low efficiency and increased side effects. Paeonol, a major component of the traditional Chinese medicine Cortex Moutan, has been applied in treating PMDD in China with satisfactory results, but the therapeutic mechanism is not fully understood. This study aims to evaluate the therapeutic effects and pharmacological mechanisms of paeonol on the main psychiatric symptoms and hippocampal damage in PMDD. We established a premenstrual irritability rat model by the resident-intruder paradigm and performed elevated plus maze and social interactions. And we employed the HE and Nissl staining techniques to observe the therapeutic effect of paeonol on hippocampal damage in PMDD rats. Subsequently, Elisa, qRT-PCR Array, Western Blotting, and cell models were utilized to elucidate the underlying molecular mechanisms through which paeonol intervenes in treating PMDD. In this study, we demonstrated the therapeutic effects of paeonol on irritability, anxiety, and social withdrawal behaviors in rats. In addition, we found that paeonol significantly reduced the serum corticosterone (CORT) level, improved hippocampal morphological structure and neuron number, and reduced hippocampal neuron apoptosis in PMDD rats. Paeonol reduced GRM5, GABBR2, ß-arrestin2, and GRK3 expression levels in hippocampal brain regions of PMDD rats and activated the cAMP/PKA signaling pathway. Inhibitor cell experiments showed that paeonol specifically ameliorated hippocampal injury by modulating the ß-arrestin2/PDE4-cAMP/PKA signaling pathway. The present study demonstrates, for the first time, that paeonol exerts a therapeutic effect on periodic psychotic symptoms and hippocampal injury in PMDD through inhibiting GRM5/GABBR2/ß-arrestin2 and activating cAMP-PKA signaling pathway. These findings enhance our understanding of the pharmacological mechanism underlying paeonol and provide a solid scientific foundation for its future clinical application.