Bu-Shen-Ning-Xin decoction ameliorates premature ovarian insufficiency by suppressing oxidative stress through rno_circRNA_012284/rno_miR-760-3p/HBEGF pathway.

BACKGROUND: POI (premature ovarian insufficiency) refers to premature and rapid decline of ovarian reserve function in women before the age of 40, which can be manifested as menstrual disorders, endocrine abnormalities and low fertility. Bu-Shen-Ning-Xin decoction (BSNXD) has been found to have therapeutic effects on POI. Nevertheless, how it exerts therapeutic effects remains elusive. PURPOSE: This research aims to clarify the pharmacological mechanisms of BSNXD. METHODS: We applied Ultra Performance Liquid Chromatography (UPLC) to identify the main components of BSNXD.4-vinylcyclohexene diepoxide(VCD)was used to induce POI models. ELISA detected the serum level of hormones. H&E staining evaluated the morphology of ovarian tissues.CircRNA and mRNA expression profiles in the ovaries of both POI rats and those treated with BSNXD were detected. Then, dysregulated circRNAs and mRNAs that were potentially altered by BSNXD were screened. Network pharmacology analysis was performed to identify drug targets of BSNXD active ingredients. A circRNA-miRNA-mRNA network and an oxidative stress(OS)-related subnetwork were constructed. Expression of rno_circRNA_012284, rno_miR-760-3p, and HBEGF(Heparin-binding epidermal growth factor-like growth factor) was measured by RT-PCR and their binding were verified by dual-luciferase reporter assays. ROS was measured through DCFH-DA fluorescence probes. The HBEGF target was selected for molecular docking with key active ingredients.Surface plasmon resonance(SPR) was applied to verify the binding ability and affinity between components and HBEGF. RESULTS: UPLC analysis indicated that 6 chemical compounds including berberine, paeoniflorin, morroniside,gallic acid, loganin, baicalin were identified.Elevated FSH and LH levels, suppressed E2 and AMH levels in the serum, and inhibited follicles and corpus luteums in the ovarian tissues of VCD-induced rats were notably reversed by BSNXD.In total, 992 up- and 1135 down-regulated circRNAs, and 205 up- and 243 down-regulated mRNAs were found in POI rat ovaries following BSNXD administration. Furthermore, 198 drug targets of BSNXD were identified. An OS-related and BSNXD-targeted ceRNA subnetwork composed of rno_circRNA_012284/rno_miR-760-3p/HBEGF was established. rno_circRNA_012284 and HBEGF were up-regulated and rno_miR-760-3p was down-regulated in POI ovarian granulosa cells (OGCs) after BSNXD administration. rno_circRNA_012284 was a sponge of rno_miR-760-3p to elevate HBEGF expression. Moreover, rno_circRNA_012284 overexpression alleviated POI-induced excessive ROS generation in ovarian granulosa cells, while rno_circRNA_012284 inhibition exerted the opposite effect. Finally,molecular docking speculated active ingredients of each herb acted on HBEGF to reduce the OS. SPR tests showed that Berberine,Baicalein,Quercetin,Pachymic acid,Paeoniflorin exhibited satisfying affinity with HBEGF protein. CONCLUSION: This study demonstrates that BSNXD ameliorates POI partly by attenuating OS in ovarian granulosa cells via rno_circRNA_012284/rno_miR-760-3p/HBEGF axis, uncovering the pharmacological mechanisms of BSNXD in alleviating POI.

Combination of pemetrexed with bevacizumab for non-small-cell lung cancer: a meta-analysis study.

BACKGROUND: Combining pemetrexed with bevacizumab may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of pemetrexed addition to bevacizumab on treatment efficacy for NSCLC. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pemetrexed addition to bevacizumab on treatment efficacy in patients with NSCLC. Overall survival and progression-free survival were included in this meta-analysis. RESULTS: Four RCTs were finally included in the meta-analysis. Overall, compared with bevacizumab for NSCLC, pemetrexed addition showed significantly improved overall survival (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.76 to 0.99; P = 0.03), survival rate (odd ratio [OR] = 1.41; 95% CI = 1.06 to 1.86; P = 0.02), progression-free survival (HR = 0.63; 95% CI = 0.55 to 0.72; P < 0.00001) and progression-free survival rate (OR = 1.92; 95% CI = 1.38 to 2.67; P < 0.00001), but led to the increase in grade ≥ 3 adverse events (OR = 2.15; 95% CI = 1.62 to 2.84; P < 0.00001). CONCLUSIONS: Pemetrexed addition may be effective to improve treatment efficacy for NSCLC compared to bevacizumab treatment.

Total astragalus saponins attenuate primary sclerosing cholangitis in mice by upregulation of TGR5.

Total astragalus saponins (TAS) are the main active components of astragali radix, and have potent anti-hepatic fibrosis effect. However, the therapeutic efficacy of TAS and their potential mechanisms in the treatment of primary sclerosing cholangitis (PSC) remain unclear. In this study, two mouse models of PSC, including 3,5-Diethoxycarbonyl-1,4-Dihydro-2,4,6-Collidine (DDC)-induced PSC and Mdr2-/- spontaneous PSC, and the Tgr5-/- mice were used to investigate the therapeutic effect and mechanisms of TAS. Treatment with TAS, particularly with a dose of 56 mg/kg, significantly ameliorated the PSC-related liver injury, cholestasis, collagen deposition, ductular reaction (DR), and fibrosis in the DDC-induced and Mdr2-/-spontaneous PSC mice. Furthermore, treatment with TAS significantly mitigated the PSC-related inflammatory responses in vivo and HIBEpiC cells by inhibiting the expression of TNF-α, IL-6, and IL-1ß. Mechanistically, treatment with TAS rescued the PSC-decreased hepatic TGR5 expression to attenuate the NF-κB p65 phosphorylation. Notably, the therapeutic efficacy of TAS on PSC in DDC-induced mice was abrogated in Tgr5-/- mice, suggesting the anti-PSC effect of TAS may depend on enhancing TGR5 expression. In conclusion, TAS ameliorated DR, inflammation and liver fibrosis in both models of PSC mice by rescuing TGR5 expression. Our findings may aid in the design of new therapeutic strategies for the treatment of PSC.

Structure engineering with sodium doping for cobalt-free Li-rich layered oxide toward improving electrochemical stability.

Structure engineering of the Li-rich layered cathodes to overcome insufficient structural stability and the rapid decay of capacity and voltage is crucial for commercializing of the materials for the lithium-ion batteries. Alkali metal element doping at the lithium sites has proven to be a feasible approach to boost the performance of the Li-rich layered oxides. Herein, the Na+-doping strategy in the lithium slabs is introduced to modify the structure of the cobalt-free layered Li-rich oxide, Li1.2Ni0.2Mn0.6O2. It is revealed that the doped Na+ ions can promote the activation of the Li2MnO3 phase, endowing the materials with high initial discharge capacity of 284.2 mAh g-1 at 0.1C. Due to the pillaring effect of the doped Na+ ions in the lithium slabs and the induced formation of oxygen vacancies, the electrochemical stability of the material is significantly improved, providing a capacity retention of 94.0 % after 100 cycles at 0.5C. The voltage decay per cycle is only 2.0 mV, less than 3.2 mV of the Li1.2Ni0.2Mn0.6O2. The results suggest that the facile strategy of introducing Na+ ions into the lithium slabs is an efficient approach for optimizing structure design of the Li-rich layered oxides for the lithium-ion batteries.

Loureirin C improves mitochondrial function by promoting NRF2 nuclear translocation to attenuate oxidative damage caused by renal ischemia-reperfusion injury.

Acute kidney injury (AKI) is a common clinical syndrome worldwide, with no effective treatment strategy. Renal ischemia-reperfusion (IR) injury is one of the main AKI features, and the excessive reactive oxygen species (ROS) production during reperfusion causes severe oxidative damage to the kidney. Loureirin C (LC), an active ingredient in the traditional Chinese medicine Chinese dragon's blood, possesses excellent antioxidative properties, but its role in renal IR injury is not clear. In this study, we evaluated the protective effects of LC against renal IR injury in vivo and in vitro by establishing a mice renal IR injury model and a human proximal renal tubular epithelial cell (HK-2) hypoxia/reoxygenation (HR) model. We found that LC ameliorated renal function and tissue structure injury and inhibited renal oxidative stress and ferroptosis in vivo. In vitro, LC scavenged ROS and attenuated mitochondrial dysfunction in HK-2 cells, thereby inhibiting oxidative cellular injury. Furthermore, we found that LC effectively promoted nuclear factor erythroid 2-related factor 2 (NRF2) nuclear translocation and activated downstream target genes heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) to enhance cellular antioxidant function. Moreover, NRF2 knockdown and pharmacological inhibition of NRF2 partially eliminated the protective effect of LC. These results confirm that LC can effectively inhibit renal IR injury, and the mechanism may be associated with NRF2 activation by LC.

Preparation of a novel type I feline coronavirus virus-like particle vaccine and its immunogenicity in mice and cats.

Feline coronavirus (FCoV) infection is a leading cause of death in cats. In this study, we produced FCoV-I virus-like particles (VLPs) containing E, M, N, and S proteins using a baculovirus expression system and mixed VLPs with the adjuvants MF59 and CpG 55.2 to prepare an VLP/MF59/CpG vaccine. After immunization of mice with the vaccine, IgG specific antibodies titers against S and N proteins increased to 1:12,800, and IFN-γ+ and IL-4+ splenocytes were significantly increased. Following immunization of FCoV-negative cats, the S protein antibodies in immunized cats (5/5) increased significantly, with a peak of 1:12,800. Notably, after booster vaccination in FCoV-positive cats, a significant reduction in viral load was observed in the feces of partial cats (4/5), and the FCoV-I negative conversion was found in two immunized cats (2/5). Therefore, the VLP/MF59/CpG vaccine is a promising candidate vaccine to prevent the FCoV infection.

Discovery of 23,24-diols containing ergosterols with anti-neuroinflammatory activity from Penicillium citrinum TJ507.

Citristerones A-E (1-5), five new 23,24-diols containing ergosterols, along with three known analogues, were isolated from the endophytic fungus Penicillium citrinum TJ507 obtained from Hypericum wilsonii N. Robson. Their structures and absolute configurations were determined by NMR, HRESIMS, Snatzke's method, X-ray diffraction analyses and ECD calculation. Subsequently, the anti-neuroinflammatory effects of these isolates were screened using lipopolysaccharide (LPS)-induced BV-2 microglial cells, and citristerone B (2) showed outstanding anti-neuroinflammatory activity, with IC50 value of 0.60 ± 0.04 µM. Moreover, immunofluorescence and western blot analysis suggested that citristerone B not only reduced the release of nitric oxide (NO) and proinflammatory cytokines in LPS-induced BV-2 microglial cells, but also significantly inhibited the expression of TNF-α, iNOS and NF-κB, along with the production of cellular ROS.

A Comprehensive Review of the Global Epidemiology, Clinical Management, Socio-Economic Impacts, and National Responses to Long COVID with Future Research Directions.

Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID's epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management; Conclusions: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Addressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.

Identification of potential biomarkers of leprosy: A study based on GEO datasets.

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.

Construction and application of a novel WGAN-CNN-based predicting approach for dust concentration at underground coal mine working faces.

To enhance the real-time monitoring and early-warning capabilities for dust disasters in underground coal mine, this paper presents a novel WGAN-CNN-based prediction approach to predict the dust concentration at underground coal mine working faces. Dust concentration, wind speed, temperature, and methane concentration were collected as the original data due to their nonlinear relationship. The consistency between the generated and original data distributions was verified through PCA dimensionality reduction analysis. The predictive performance of this approach was assessed using five metrics (R2, EVS, MSE, RMSE, and MAE) and compared with three other algorithms (Random Forest Regressor, MLP Regressor, and LinearSVR). The findings indicate that a majority of the generated data falls within the distribution range of the real dataset, exhibiting reduced levels of volatility and dispersion. The R2 values of prediction results are all above 98%, and the MSE values are between 0.0007 and 0.0106. The proposed approach exhibits superior predictive accuracy and robust model generalization capabilities compared to alternative algorithms, thereby enhancing the real-time monitoring and early-warning level of dust disasters in underground coal mine. This will facilitate the realization of advanced prevention and control measures for dust disasters, showcasing a wide range of potential applications.

Hybrid Cas12a Variants with Relaxed PAM Requirements Expand Genome Editing Compatibility.

Cas12a is a widely used programmable nuclease for genome editing across a variety of organisms, but its application is limited by its PAM recognition restriction. To alleviate these PAM constraints, protein engineering efforts have been applied to expand the PAM recognition range. In this study, we designed and constructed 990 synthetic hybrid Cas12a chimeras through domain shuffling and screened an efficient hybrid Cas12a (ehCas12a) that could recognize a broad range PAM of 5'-TYYN-3' (Y is T or C and N is A, T, C, or G). Furthermore, we constructed an ehCas12a variant, ehCas12a RRVR (T167R/N572R/K578V/N582R), with expanded PAM preference to 5'-TNYN, TWRV-3' (W is A or T, R is A or G, and V is A, C, or G), which can efficiently recognize -2* A/G PAMs that are barely recognized by Cas12a-type proteins and their mutants. Finally, we demonstrated that the DNase-inactivated ehCas12a RRVR base editor (dehCas12a RRVR-BE) was capable of targeting noncanonical PAMs in vivo and disease-related loci for potential therapeutic applications. Overall, our findings highlight the modular design and reconfiguration of Cas proteins for enhanced functionality.

Multi-spectroscopic characterization of organic salt components in medicinal plant.

The characterization of structure of organic salts in complex mixtures has been a difficult problem in analytical chemistry. In the analysis of Scutellariae Radix (SR), the pharmacopoeia of many countries stipulates that the quality control component is baicalin (≥9% by high performance liquid chromatography (HPLC)). The component with highest response in SR was also baicalin detected by liquid chromatography-mass spectrometry (LC-MS). However, in the attenuated total reflection Fourier transform infrared spectroscopy, the carbonyl peak of glucuronic acid of baicalin did not appear in SR. The results of element analysis, time of flight secondary ion mass spectrometry, matrix assisted laser desorption ionization mass spectrometry and solid-state nuclear magnetic resonance all supported the existence of baicalin magnesium salt. Based on this, this study proposes an analysis strategy guided by infrared spectroscopy and combined with multi-spectroscopy techniques to analyze the structure of organic salt components in medicinal plant. It is meaningful for the research of mechanisms, development of new drugs, and quality control.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes.

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.

Radar Micro-Doppler Signature Generation Based on Time-Domain Digital Coding Metasurface.

Micro-Doppler effect is a vital feature of a target that reflects its oscillatory motions apart from bulk motion and provides an important evidence for target recognition with radars. However, establishing the micro-Doppler database poses a great challenge, since plenty of experiments are required to get the micro-Doppler signatures of different targets for the purpose of analyses and interpretations with radars, which are dramatically limited by high cost and time-consuming. Aiming to overcome these limits, a low-cost and powerful simulation platform of the micro-Doppler effects is proposed based on time-domain digital coding metasurface (TDCM). Owing to the outstanding capabilities of TDCM in generating and manipulating nonlinear harmonics during wave-matter interactions, it enables to supply rich and high-precision electromagnetic signals with multiple micro-Doppler frequencies to describe the micro-motions of different objects, which are especially favored for the training of artificial intelligence algorithms in automatic target recognition and benefit a host of applications like imaging and biosensing.

Sleep Duration and Risk of Periodontitis-A Systematic Review and Meta-Analysis.

Periodontitis, with a high prevalence in the whole population, is the main cause of tooth loss. Some studies have revealed that sleep duration may be related to periodontitis, however, the opinions are not consistent. This meta-analysis was carried out to study the potential relationship between sleep duration and periodontitis. A search of relevant articles was conducted on Embase, PubMed, Cochrane Library, and Web of Science. Papers published until the end of November 2022 reporting associations between sleep duration and periodontitis were considered. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated to assess the association. Software STATA 14.0 was employed to conduct this analysis. A total of 11 cross-sectional studies were included. Our study showed neither short sleep duration (SSD) nor long sleep duration (LSD) were associated with periodontitis (SSD: OR = 1.04, 95% CI: 0.83, 1.29; LSD: OR = 1.12, 95% CI: 0.94, 1.23), while higher prevalence was observed when sleep duration ≤5 h (OR = 1.41, 95% CI: 1.33, 1.51). In addition, both SSD and LSD were not associated with severe periodontitis (SSD: OR = 0.94, 95% CI: 0.75, 1.16; LSD: OR = 1.19, 95% CI: 0.80, 1.76). In conclusion, the present review indicated that too little sleep duration (≤5 h) significantly increased the risk of periodontitis. However, the evidence is limited due to cross-sectional design of most studies, Hence longitudinal studies should be conducted to support this finding.

Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer.

Bladder cancer (BCa) is one of the most common malignancies affecting men. Oncogenic transcription factors function as an important regulator in the progression of human cancer. In our study, we aimed to construct artificial circular non-coding RNAs (acircRNAs) consisting of three functional units that mimic the CRISPR-Cas system and elucidate its therapeutic role in bladder cancer. Additionally, the compare of the efficiency in regulating gene expression between acircRNA and CRISPR-dCas systems was performed. We connected the cDNA sequences of TFs aptamer and constructed a circRNA. To demonstrate the platform's practicality, ß-catenin and NF-κB were chosen as functional targets, while T24 and 5637 cell lines served as test models. Real-time Quantitative PCR (qPCR), double luciferase assay and related phenotype assay were used to detect the expression of related genes and the therapeutic effect. To elucidate the functionality of acircRNAs, luciferase vectors capable of detecting ß-catenin and NF-κB expression were employed to assess the inhibitory impact of acircRNA on ß-catenin and NF-κB. Consequently, the optimal combination involving acircRNA-3 was determined. Next, qPCR assay was employed to assess the relative expression levels of target downstream genes following acircRNA treatment. The expression of c-myc and cyclin D1 were used to determine the function of ß-catenin, while Bcl-XL and TRAF1 were used to determine that of NF-κB. The acircRNAs inhibited the ß-catenin and NF-κB related signaling in BCa cells specifically. CD63-HuR fusion protein was used to loading acircRNA into exosomes. The results showed that acircRNA could inhibit the activity of the target transcription factors, and the inhibitory effect was better than that of CRIPSR-dCas9-KRAB. Furthermore, functional experiments demonstrated that the transfection of acircRNA in bladder cells resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. In conclusion, our synthetic gene device exhibited anti-tumor regulatory capabilities and showed greater efficiency in tumor suppression compared to the CRISPR-dCas9-KRAB system. Therefore, our device provides a new strategy for cancer treatment and could be a useful strategy for cancer cells.

[Synthetic phenolic compounds perturb lipid metabolism and induce obesogenic effects].

Given continuous development in society and the economy, obesity has become a global epidemic, arousing great concern. In addition to genetic and dietary factors, exposure to environmental chemicals is associated with the occurrence and development of obesity. Current research has indicated that some chemicals with endocrine-disrupting effects can affect lipid metabolism in vivo, causing elevated lipid storage. These chemicals are called "environmental obesogens". Synthetic phenolic compounds (SPCs) are widely used in industrial and daily products, such as plastic products, disinfectants, pesticides, food additives, and so on. The exposure routes of SPCs to the human body may include food and water consumption, direct skin contact, etc. Their unintended exposure could cause harmful effects on human health. As a type of endocrine disruptor, SPCs interfere with adipogenesis and lipid metabolism, exhibiting the characteristics of environmental obesogens. Because SPCs have similar phenolic structures, gathering information on their influences on lipid metabolism would be helpful to understand their structure-related effects. In this review, three commonly used research methods for screening environmental obesogens, including in vitro testing for molecular interactions, cell adipogenic differentiation models, and in vivo studies on lipid metabolism, are summarized, and the advantages and disadvantages of these methods are compared and discussed. Based on both in vitro and in vivo data, three types of SPCs, including bisphenol A (BPA) and its analogues, alkylphenols (APs), and synthetic phenolic antioxidants (SPAs), are systematically discussed in terms of their ability to disrupt adipogenesis and lipid metabolism by focusing on adipose and hepatic tissues, among others. Common findings on the effects of these SPCs on adipocyte differentiation, lipid storage, hepatic lipid accumulation, and liver steatosis are described. The underlying toxicological mechanisms are also discussed from the aspects of nuclear receptor transactivation, inflammation and oxidative stress regulation, intestinal microenvironment alteration, epigenetic modification, and some other signaling pathways. Future research to increase public knowledge on the obesogenic effects of emerging chemicals of concern is encouraged.

Cocrystallization improves the tabletability of ligustrazine despite a reduction in plasticity.

Cocrystallization is an effective method for altering the tableting performance of crystals by modifying their mechanical properties. In this study, cocrystals of ligustrazine (LIG) with malonic acid (MA) and salicylic acid (SA) were investigated to better understand how modifying crystal structure can affect tableting properties. LIG suffered from overcompression at high pressures despite its high plasticity. Both LIG-MA and LIG-SA displayed lower plasticity than LIG, which was confirmed by both an in-die Heckel and energy framework analyses. The LIG-MA cocrystal displayed slightly worse tabletability than LIG, as expected from its lower plasticity. However, LIG-SA surprisingly showed improved tabletability despite its lower plasticity. This was explained by the higher bonding strength of LIG-SA compared with LIG. This work not only provided new examples of tabletability modulation through crystal engineering but also highlighted the risk of failed tabletability predictions based on plasticity alone. Instead, more reliable tabletability predictions of different crystal forms must consider the bonding area - bonding strength interplay.

Dual modification of phosphate toward improving electrochemical performance of LiNiO2 cathode materials.

Lithium nickel oxide (LiNiO2) cathode materials are featured with high capacity and low cost for rechargeable lithium-ion batteries but suffer from severe structure and interface instability. Bulk doping together with surface coating has been proven to be an efficient approach to improve the inner structure and interfacial stability of the LiNiO2 cathode material. Nevertheless, the role of anion doping seems to be quite different from that of cation doping, and a deep insight will be desirable for the structure design of the LiNiO2 cathode material. In this paper, PO43--doped and Li3PO4-coating of dual modification of LiNiO2 are achieved via a facile approach. It is demonstrated that the PO43- anions are doped into the tetrahedron vacant sites of the crystal structure, alleviating the phase transition and improving the reversibility of crystal structure. Besides, the Li3PO4 coating layer ameliorates the interface stability to restrain the side reactions. Therefore, the dual modification enhances overall structural stability of the material to provide excellent performance. Moreover, the consumption of the Li residues by the formation of Li3PO4 coating layer, and the enlarged interlayer spacing of the crystal structure by PO43- doping can facilitate the Li+ ions diffusion, resulting in a superior rate capability.