Altered Liver Enzyme Markers in Patients with Asymptomatic, and Mild Omicron Infection: A Retrospective Study.

Purpose: The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections. Patients and Methods: A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0. Results: Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels. Conclusion: Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.

Knowledge graph confidence-aware embedding for recommendation.

Knowledge graphs (KG) are vital for extracting and storing knowledge from large datasets. Current research favors knowledge graph-based recommendation methods, but they often overlook the features learning of relations between entities and focus excessively on entity-level details. Moreover, they ignore a crucial fact: the aggregation process of entity and relation features in KG is complex, diverse, and imbalanced. To address this, we propose a recommendation-oriented KG confidence-aware embedding technique. It introduces an information aggregation graph and a confidence feature aggregation mechanism to overcome these challenges. Additionally, we quantify entity confidence at the feature and category levels, improving the precision of embeddings during information propagation and aggregation. Our approach achieves significant improvements over state-of-the-art KG embedding-based recommendation methods, with up to 6.20% increase in AUC and 8.46% increase in GAUC, as demonstrated on four public KG datasets2.

Proteomic Characterization of Transfusable Blood Components: Fresh Frozen Plasma, Cryoprecipitate, and Derived Extracellular Vesicles via Data-Independent Mass Spectrometry.

Extracellular vesicles (EVs) are a heterogeneous collection of particles that play a crucial role in cell-to-cell communication, primarily due to their ability to transport molecules, such as proteins. Thus, profiling EV-associated proteins offers insight into their biological effects. EVs can be isolated from various biological fluids, including donor blood components such as cryoprecipitate and fresh frozen plasma (FFP). In this study, we conducted a proteomic analysis of five single donor units of cryoprecipitate, FFP, and EVs derived from these blood components using a quantitative mass spectrometry approach. EVs were successfully isolated from both cryoprecipitate and FFP based on community guidelines. We identified and quantified approximately 360 proteins across all sample groups. Principal component analysis and heatmaps revealed that both cryoprecipitate and FFP are similar. Similarly, EVs derived from cryoprecipitate and FFP are comparable. However, they differ between the originating fluids and their derived EVs. Using the R-package MS-DAP, differentially expressed proteins (DEPs) were identified. The DEPs for all comparisons, when submitted for gene enrichment analysis, are involved in the complement and coagulation pathways. The protein profile generated from this study will have important clinical implications in increasing our knowledge of the proteins that are associated with EVs derived from blood components.

Deep Single Image Defocus Deblurring via Gaussian Kernel Mixture Learning.

This paper proposes an end-to-end deep learning approach for removing defocus blur from a single defocused image. Defocus blur is a common issue in digital photography that poses a challenge due to its spatially-varying and large blurring effect. The proposed approach addresses this challenge by employing a pixel-wise Gaussian kernel mixture (GKM) model to accurately yet compactly parameterize spatially-varying defocus point spread functions (PSFs), which is motivated by the isotropy in defocus PSFs. We further propose a grouped GKM (GGKM) model that decouples the coefficients in GKM, so as to improve the modeling accuracy with an economic manner. Afterward, a deep neural network called GGKMNet is then developed by unrolling a fixed-point iteration process of GGKM-based image deblurring, which avoids the efficiency issues in existing unrolling DNNs. Using a lightweight scale-recurrent architecture with a coarse-to-fine estimation scheme to predict the coefficients in GGKM, the GGKMNet can efficiently recover an all-in-focus image from a defocused one. Such advantages are demonstrated with extensive experiments on five benchmark datasets, where the GGKMNet outperforms existing defocus deblurring methods in restoration quality, as well as showing advantages in terms of model complexity and computational efficiency.

[Effects of different genotypes soybean and maize intercropping on soil phosphorus fractions and crop phosphorus uptake]. / ä¸åŒåŸºå› åž‹å¤§è±†ä¸ŽçŽ‰ç±³é—´ä½œå¯¹åœŸå£¤ç£·ç»„åˆ†ä¸Žä½œç‰©ç£·å¸æ”¶çš„å½±å“.

Reasonable soybean-maize intercropping mode can effectively promote soil phosphorus turnover and crop phosphorus absorption, and reduce phosphorus fertilizer input. To optimize phosphorus (P)-use efficiency in soybean/maize intercropping system, we intercropped two genotypes of soybean with maize to investigate the rhizosphere processes and mechanisms underlying soil biological P fractions and crop P uptake. The results showed that intercropping significantly depleted the rhizosphere soluble inorganic P (CaCl2-P) content in soybean genotype Yuechun 03-3, without impact on the P fractions in the rhizosphere of soybean Essex. Similarly, intercropping significantly increased biomass and P uptake of soybean genotype Yuechun 03-3 by 42.2% and 46.9%, respectively, compared to monoculture. However, it did not affect P uptake and biomass of soybean Essex and maize. Intercropping significantly increased both the total root length and the quantity of root exudates in Yuechun 03-3 by 19.7% and 138.1%, respectively. There was a significant positive correlation between P uptake and total root length in Yuechun 03-3, while a significant negative correlation between soluble inorganic P content and P uptake. In summary, intercropping of soybean and maize exhibited noticeable genotype differences in its impact on soil P fractions and crop P uptake. Intercropping has the potential to improve soybean P uptake and rhizosphere P turnover, mainly by increasing root length and root exudates of P-efficient genotype. The study would provide scientific evidence for optimizing the pairing of soybean and maize varieties in intercropping systems, thereby enhancing phosphorus utilization efficiency and reducing fertilizer inputs.

Advances in Cyclodextrins and Their Derivatives in Nano-Delivery Systems.

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.

Important yet Overlooked HONO Source from Aqueous-phase Photochemical Oxidation of Nitrophenols.

Nitrites (NO2-/HONO), as the primary source of hydroxyl radicals (•OH) in the atmosphere, play a key role in atmospheric chemistry. However, the current understanding of the source of NO2-/HONO is insufficient and therefore hinders the accurate quantification of atmospheric oxidation capacity. Herein, we highlighted an overlooked HONO source by the reaction between nitrophenols (NPs) and •OH in the aqueous phase and provided kinetic data to better evaluate the contribution of this process to atmospheric HONO. Three typical NPs, including 4-nitrophenol (4NP), 2-nitrophenol (2NP), and 4-nitrocatechol (4NC), underwent a denitration process to form aqueous NO2- and gaseous HONO through the •OH oxidation, with the yield of NO2-/HONO varied from 15.0 to 33.5%. According to chemical composition and structure analysis, the reaction pathway, where the ipso addition of •OH to the NO2 group on 4NP generated hydroquinone, can contribute to more than 61.9% of the NO2-/HONO formation. The aqueous photooxidation of NPs may account for HONO in the atmosphere, depending on the specific conditions. The results clearly suggest that the photooxidation of NPs should be considered in the field observation and calculation to better evaluate the HONO budget in the atmosphere.

[Dobutamine Enhances the Targeted Inhibitory Effect of Quizartinib on FLT3-ITD Mutant Acute Myeloid Leukemia].

OBJECTIVE: To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia (AML) cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML. METHODS: FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group, dobutamine treatment group, quizartinib treatment group, and dobutamine combined with quizartinib treatment group. Cell viability, ROS levels, and apoptosis rate were detected by CCK-8, Flow cytometry, respectively, as well as the expression of YAP1 protein by Western blot. RESULTS: Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines. Compared with the control group, the dobutamine group exhibited a significant increase in ROS levels (P < 0.01), an increase in apoptosis rates (P < 0.05), and a decrease in YAP1 protein expression (P < 0.01), and decreased YAP1 expression (P < 0.05). CONCLUSION: Dobutamine as a monotherapy can inhibit theproliferation of FLT3-ITD mutated AML cells, inducing apoptosis. Additionally, the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML. The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type, leading to an increase in ROS levels and exerting its anti-tumor effects.

Accelerating the calculation of electron-phonon coupling strength with machine learning.

The calculation of electron-phonon couplings (EPCs) is essential for understanding various fundamental physical properties, including electrical transport, optical and superconducting behaviors in materials. However, obtaining EPCs through fully first-principles methods is notably challenging, particularly for large systems or when employing advanced functionals. Here we introduce a machine learning framework to accelerate EPC calculations by utilizing atomic orbital-based Hamiltonian matrices and gradients predicted by an equivariant graph neural network. We demonstrate that our method not only yields EPC values in close agreement with first-principles results but also enhances calculation efficiency by several orders of magnitude. Application to GaAs using the Heyd-Scuseria-Ernzerhof functional reveals the necessity of advanced functionals for accurate carrier mobility predictions, while for the large Kagome crystal CsV3Sb5, our framework reproduces the experimentally observed double domes in pressure-induced superconducting phase diagrams. This machine learning framework offers a powerful and efficient tool for the investigation of diverse EPC-related phenomena in complex materials.

The complete chloroplast genome of Rhododendronambiguum and comparative genomics of related species.

Rhododendron Linnaeus, 1753, the largest genus of woody plants in the Northern Hemisphere, includes some of the most significant species in horticulture. Rhododendronambiguum Hemsl, 1911, a member of subsection Triflora Sleumer 1947, exemplifies typical alpine Rhododendron species. The analysis of the complete chloroplast genome of R.ambiguum offers new insights into the evolution of Rhododendron species and enhances the resolution of phylogenetic relationships. This genome is composed of 207,478 base pairs, including a pair of inverted repeats (IRs) of 47,249 bp each, separated by a large single-copy (LSC) region of 110,367 bp and a small single-copy (SSC) region of 2,613 bp. It contains 110 genes: 77 protein-coding genes, 29 tRNAs, four unique rRNAs (4.5S, 5S, 16S, and 23S), with 16 genes duplicated in the IRs. Comparative analyses reveal substantial diversity in the Rhododendron chloroplast genome structures, identifying a fourth variant pattern. Specifically, four highly divergent regions (trnI-rpoB, ndhE-psaC, rpl32-ndhF, rrn16S-trnI) were noted in the intergenic spacers. Additionally, 76 simple sequence repeats were identified. Positive selection signals were detected in four genes (cemA, rps4, rpl16, and rpl14), evidenced by high Ka/Ks ratios. Phylogenetic reconstruction based on two datasets (shared protein-coding genes and complete chloroplast genomes) suggests that R.ambiguum is closely related to R.concinnum Hemsley, 1889. However, the phylogenetic positions of subsection Triflora Pojarkova, 1952 species remain unresolved, indicating that the use of complete chloroplast genomes for phylogenetic research in Rhododendron requires careful consideration. Overall, our findings provide valuable genetic information that will enhance understanding of the evolution, molecular biology, and genetic improvement of Rhododendron spieces.

Different endometrial preparation protocols on first frozen-thawed embryo transfer outcomes after hysteroscopic polypectomy: A retrospective cohort study.

OBJECTIVE: To evaluate the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) following hysteroscopic polypectomy. METHODS: This was a retrospective clinical cohort study involving 464 patients who underwent their first FET after polyp resection between January 2021 and July 2023. The cohorts were categorized into three groups: the natural cycle (NC) group (n = 139), the ovarian induction (OI) group (n = 117), and the hormone replacement therapy (HRT) group (n = 208). RESULTS: In the initial unadjusted analysis, both NC and OI cycles exhibited similar pregnancy rates but were associated with significantly higher implantation rate (56.5%, 57.1% vs 42.0%, P < 0.001), clinical pregnancy rate (73.4%, 74.4% vs 57.2%, P = 0.001), and ongoing pregnancy rate (OPR; 67.6%, 63.2% vs 51.0%, P = 0.005) compared to the HRT group. Additionally, the three groups demonstrated comparable abortion rate (7.8%, 14.9% vs 10.9%, P = 0.299). After adjusting for potential confounders in the multiple logistic regression model, the HRT protocol resulted in a 54% significantly lower OPR compared to the NC protocol (adjusted odds ratio [aOR] = 0.46, 95% confidence interval [CI]: 0.28-0.77; P = 0.003). Meanwhile, the OPR difference between the OI protocol and the NC protocol remained insignificant (OI vs NC: aOR = 0.62, 95% CI: 0.35-1.12; P = 0.112). CONCLUSION: The ovulatory-FET scheme (NC and OI) following hysteroscopic polyp resection displayed promising clinical outcomes compared with HRT-FET scheme. The regimen without exogenous estrogen administration should be prioritized for endometrial preparation protocol after polypectomy.

Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis. METHODS: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT. RESULTS: The expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells. CONCLUSIONS: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.

Extracellular vesicles in fresh frozen plasma and cryoprecipitate: Impact on in vitro endothelial cell viability.

BACKGROUND: Transfusion-related acute lung injury (TRALI) remains a major contributor to transfusion-associated mortality. While the pathogenesis of TRALI remains unclear, there is evidence of a role for blood components. We therefore investigated the potential effects of fresh frozen plasma (FFP), cryoprecipitate, and extracellular vesicles (EVs) derived from these blood components, on the viability of human lung microvascular endothelial cells (HLMVECs) in vitro. METHODS: EVs were isolated from FFP and cryoprecipitate using size-exclusion chromatography and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscopy. The potential effects of these blood components and their EVs on HLMVEC viability (determined by trypan blue exclusion) were examined in the presence and absence of neutrophils, either with or without prior treatment of HLMVECs with LPS. RESULTS: EVs isolated from FFP and cryoprecipitate displayed morphological and biochemical properties conforming to latest international criteria. While FFP, cryoprecipitate, and EVs derived from FFP, each reduced HLMVEC viability, no effect was observed for EVs derived from cryoprecipitate. CONCLUSION: Our findings demonstrate clear differences in the effects of FFP, cryoprecipitate, and their respective EVs on HLMVEC viability in vitro. Examination of the mechanisms underlying these differences may lead to an improved understanding of the factors that promote development of TRALI.

[Clinical efficacy of nusinersen sodium in the treatment of children with spinal muscular atrophy]. / è¯ºè¥¿é‚£ç”Ÿé’ æ²»ç–—è„Šé«“æ€§è‚ŒèŽç¼©ç—‡å„¿ç«¥çš„ä¸´åºŠåˆ†æž.

OBJECTIVES: To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024. RESULTS: Compared with the baseline data, 67% (8/12), 74% (35/47), and 74% (35/47) of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module, respectively, and the distance of 6-minute walking test increased from 207.00 (179.00, 281.50) meters to 233.00 (205.25, 287.50) meters (P<0.05) after nusinersen sodium treatment. Of all 50 children with SMA, 24 (48%) showed good tolerability after administration, with no significant or persistent abnormalities observed in 2 034 laboratory test results, and furthermore, there were no serious or immunological adverse events related to the treatment. After treatment, there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction, as well as a significant change in the level of 25-(OH) vitamin D in 15 children with vitamin D deficiency (P<0.05). CONCLUSIONS: For children with SMA, treatment with nusinersen sodium can continuously improve the response rates of motor function scales, with good tolerability and safety.

A Comprehensive Clinical Outcome Analysis of Endoscopic Vessel Harvesting for Coronary Artery Bypass Surgery.

Background: The long saphenous vein is routinely used for coronary bypass graft (CABG) surgery, and two primary techniques are commonly utilized: endoscopic vessel harvesting (EVH) and open vessel harvesting (OVH). The aim of this study was to compare the clinical outcomes of the EVH and OVH techniques used for CABG within the confines of a tertiary hospital. Methods: The clinical data of all patients subjected to either EVH or OVH for CABG surgery between 2014 and 2018 were retrospectively analyzed. Statistical analysis was performed to discern variations in the rates of postoperative complications between EVH and OVH. Results: A cohort of 1884 individuals were included in this study, 75.3% of whom underwent EVH. Notably, the incidence of postoperative leg wound complications was significantly different between the patients who underwent OVH and the patients who underwent EVH, with incidence rates of 18.6% and 32%, respectively (p < 0.001). Leg wound complications (p < 0.001; OR 1.946; 95% CI 1.528-2.477) and leg wound infections (p = 0.050, OR 1.517, 95% CI 0.999-2.303) were significantly associated with OVH. Moreover, leg wound hematoma (p = 0.039, OR = 0.402, 95% CI = 0.169-0.957) and EVH were strongly associated. Conclusions: The large sample of patients and the inclusion of a range of Asian ethnic groups provided notable insights into postoperative complications related to different modalities. EVH was associated with a lower incidence of postoperative leg wound complications, which suggests that EVH is a better modality for those undergoing CABG surgery.

Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-ß1/Smad3 pathways.

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.

Ketogenic Diets Alter the Gut Microbiome, Resulting in Decreased Susceptibility to and Cognitive Impairment in Rats with Pilocarpine-Induced Status Epilepticus.

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

Er-Dong-Xiao-Ke decoction regulates lipid metabolism via PPARG-mediated UCP2/AMPK signaling to alleviate diabetic meibomian gland dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Meibomian gland dysfunction (MGD), complicated by type 2 diabetes, is associated with a high incidence of ocular surface disease, and no effective drug treatment exists. Diabetes mellitus (DM) MGD shows a notable disturbance in lipid metabolism. Er-Dong-Xiao-Ke decoction (EDXKD) has important functions in nourishing yin, clearing heat, and removing blood stasis, which are effective in the treatment of DM MGD. AIM OF THE STUDY: To observe the therapeutic effect of EDXKD on DM MGD and its underlying molecular mechanism. MATERIALS AND METHODS: After establishing a type 2 DM (T2DM)-induced MGD rat model, different doses of EDXKD and T0070907 were administered. The chemical constituents of EDXKD were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the molecular mechanism of EDXKD in treating DM MGD was predicted using network pharmacology. Lipid metabolism in DM meibomian glands (MGs) was analyzed using LC-MS/MS, and lipid biomarkers were screened and identified. Histological changes and lipid accumulation in MGs were detected by staining, and Peroxisome proliferator-activated receptor gamma (PPARG) expression in MG acinar cells was detected by immunofluorescence. The expression of lipid metabolism-related factors was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blotting. RESULTS: EDXKD reduced lipid accumulation in the MGs and improved the ocular surface index in DM MGD rats. The main active components of EDXKD had advantages in lipid regulation. Additionally, the PPARG signaling pathway was the key pathway of EDXKD in the treatment of DM MGD. Twelve lipid metabolites were biomarkers of EDXKD in the treatment of DM MGD, and glycerophospholipid metabolism was the main pathway of lipid regulation. Moreover, EDXKD improved lipid deposition in the acini and upregulated the expression of PPARG. Further, EDXKD regulated the PPARG-mediated UCP2/AMPK signaling network, inhibited lipid production, and promoted lipid transport. CONCLUSION: EDXKD is an effective treatment for MGD in patients with T2DM. EDXKD can regulate lipids by regulating the PPARG-mediated UCP2/AMPK signaling network, as it reduced lipid accumulation in the MGs of DM MGD rats, promoted lipid metabolism, and improved MG function and ocular surface indices.

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

miR-423-5p Regulates Skeletal Muscle Growth and Development by Negatively Inhibiting Target Gene SRF.

The process of muscle growth directly affects the yield and quality of pork food products. Muscle fibers are created during the embryonic stage, grow following birth, and regenerate during adulthood; these are all considered to be phases of muscle development. A multilevel network of transcriptional, post-transcriptional, and pathway levels controls this process. An integrated toolbox of genetics and genomics as well as the use of genomics techniques has been used in the past to attempt to understand the molecular processes behind skeletal muscle growth and development in pigs under divergent selection processes. A class of endogenous noncoding RNAs have a major regulatory function in myogenesis. But the precise function of miRNA-423-5p in muscle development and the related molecular pathways remain largely unknown. Using target prediction software, initially, the potential target genes of miR-423-5p in the Guangxi Bama miniature pig line were identified using various selection criteria for skeletal muscle growth and development. The serum response factor (SRF) was found to be one of the potential target genes, and the two are negatively correlated, suggesting that there may be targeted interactions. In addition to being strongly expressed in swine skeletal muscle, miR-423-5p was also up-regulated during C2C12 cell development. Furthermore, real-time PCR analysis showed that the overexpression of miR-423-5p significantly reduced the expression of myogenin and the myogenic differentiation antigen (p < 0.05). Moreover, the results of the enzyme-linked immunosorbent assay (ELISA) demonstrated that the overexpression of miR-423-5p led to a significant reduction in SRF expression (p < 0.05). Furthermore, miR-423-5p down-regulated the luciferase activities of report vectors carrying the 3' UTR of porcine SRF, confirming that SRF is a target gene of miR-423-5p. Taken together, miR-423-5p's involvement in skeletal muscle differentiation may be through the regulation of SRF.