Preoperative prediction power of radiomics and non-radiomics methods based on MRI for early recurrence in hepatocellular carcinoma: a systemic review and meta-analysis.

OBJECTIVE: To compare radiomics and non-radiomics in predicting early recurrence (ER) in patients with hepatocellular carcinoma (HCC) after curative surgery. METHODS: We systematically searched PubMed and Embase databases. Studies with clear reference criteria were selected. Data were extracted and assessed for quality using the quality in prognosis studies tool (QUIPS) by two independent authors. All included radiomics studies underwent radiomics quality score (RQS) assessment. We calculated sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using random or fixed models with a 95%CI. Forest maps visualized the data, and summary receiver operating characteristic (sROC) curves with the area under the curve (AUC) were generated. Meta-regression and subgroup analyses explored sources of heterogeneity. We compared sensitivity, specificity, PLR, and NLR using the z-test and compared AUC values using the Delong test. RESULTS: Our meta-analysis included 10 studies comprising 1857 patients. For radiomics, the pooled sensitivity, specificity, AUC of sROC, PLR and NLR were 0.84(95%CI: 0.78-0.89), 0.80(95%CI: 0.75-0.85), 0.89(95%CI: 0.86-0.91), 4.28(95%CI: 3.48-5.27) and 0.20(95%CI: 0.14-0.27), respectively, but with significant heterogeneity (I2 = 60.78% for sensitivity, I2 = 55.79% for specificity) and potential publication bias (P = 0.04). The pooled sensitivity, specificity, AUC of sROC, PLR, NLR for non-radiomics were 0.75(95%CI:0.68-0.81), 0.78(95%CI:0.72-0.83), 0.83(95%CI: 0.80-0.86), 3.45(95%CI: 2.68-4.44) and 0.32(95%CI: 0.24-0.41), respectively. There was no significant heterogeneity in this group (I2 = 0% for sensitivity, I2 = 17.27% for specificity). Radiomics showed higher diagnostic accuracy (AUC: 0.89 vs. 0.83, P = 0.0456), higher sensitivity (0.84 vs. 0.75, P = 0.0385) and lower NLR (0.20 vs. 0.32, P = 0.0287). CONCLUSION: The radiomics from preoperative MRI effectively predicts ER of HCC and has higher diagnostic accuracy than non-radiomics. Due to potential publication bias and suboptimal RQS scores in radiomics, these results should be interpreted cautiously.

Curcumin-primed olfactory mucosa-derived mesenchymal stem cells mitigate cerebral ischemia/reperfusion injury-induced neuronal PANoptosis by modulating microglial polarization.

BACKGROUND: Cerebral ischemia-reperfusion (I/R) injury often leads to neuronal death through persistent neuroinflammatory responses. Recent research has unveiled a unique inflammatory programmed cell death mode known as PANoptosis. However, direct evidence for PANoptosis in ischemic stroke-induced neuronal death has not been established. Although it is widely thought that modulating the balance of microglial phenotypic polarization in cerebral I/R could mitigate neuroinflammation-mediated neuronal death, it remains unknown whether microglial polarization influences PANoptotic neuronal death triggered by cerebral I/R. Our prior study demonstrated that curcumin (CUR) preconditioning could boost the neuroprotective properties of olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) in intracerebral hemorrhage. Yet, the potential neuroprotective capacity of curcumin-pretreated OM-MSCs (CUR-OM-MSCs) on reducing PANoptotic neuronal death during cerebral I/R injury through modulating microglial polarization is uncertain. METHODS: To mimic cerebral I/R injury, We established in vivo models of reversible middle cerebral artery occlusion (MCAO) in C57BL/6 mice and in vitro models of oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 neurons and BV2 microglia. RESULTS: Our findings indicated that cerebral I/R injury caused PANoptotic neuronal death and triggered microglia to adopt an M1 (pro-inflammatory) phenotype both in vivo and in vitro. Curcumin pretreatment enhanced the proliferation and anti-inflammatory capacity of OM-MSCs. The CUR-OM-MSCs group experienced a more pronounced reduction in PANoptotic neuronal death and a better recovery of neurological function than the OM-MSCs group. Bioinformatic analysis revealed that microRNA-423-5p (miRNA-423-5p) expression was obviously upregulated in CUR-OM-MSCs compared to OM-MSCs. CUR-OM-MSCs treatment induced the switch to an M2 (anti-inflammatory) phenotype in microglia by releasing miRNA-423-5p, which targeted nucleotide-binding oligomerization domain 2 (NOD2), an upstream regulator of NF-kappaB (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, to attenuate PANoptotic neuronal death resulting from cerebral I/R. CONCLUSION: This results provide the first demonstration of the existence of PANoptotic neuronal death in cerebral I/R conditions. Curcumin preconditioning enhanced the ameliorating effect of OM-MSCs on neuroinflammation mediated by microglia polarization via upregulating the abundance of miRNA-423-5p. This intervention effectively alleviates PANoptotic neuronal death resulting from cerebral I/R. The combination of curcumin with OM-MSCs holds promise as a potentially efficacious treatment for cerebral ischemic stroke in the future.

Ten-year observation of corneal densitometry and associated factors following small incision lenticule extraction.

AIM: To investigate the long-term changes of corneal densitometry (CD) and its contributing elements after small incision lenticule extraction (SMILE). METHODS: Totally 31 eyes of 31 patients with mean spherical equivalent of -6.46±1.50 D and mean age 28.23±7.38y were enrolled. Full-scale examinations were conducted on all patients preoperatively and during follow-up. Visual acuity, manifest refraction, axial length, corneal thickness, corneal higher-order aberrations, and CD were evaluated. RESULTS: All surgeries were completed successfully without complications or adverse events. Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28. CD value of 0-6 mm zones in central layer was statistically significantly lower 10y postoperatively, compared with preoperative values (0-2 mmΔ=-1.62, 2-6 mmΔ=-1.24, P<0.01). There were no correlations between CD values and factors evaluated. CONCLUSION: SMILE is a safe and efficient procedure for myopia on a long-term basis. CD values get lower 10y postoperatively, whose mechanism is to be further discussed.

The Diagnostic Accuracy Between Radiomics Model and Non-radiomics Model for Preoperative of Microvascular Invasion of Solitary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: Microvascular invasion (MVI) is a key prognostic factor for hepatocellular carcinoma (HCC). The predictive models for solitary HCC could potentially integrate more comprehensive tumor information. Owing to the diverse findings across studies, we aimed to compare radiomic and non-radiomic methods for preoperative MVI detection in solitary HCC. MATERIALS AND METHODS: Articles were reviewed from databases including PubMed, Embase, Web of Science, and the Cochrane Library until April 7, 2023. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model within a 95% confidence interval (CI). Diagnostic accuracy was assessed using summary receiver-operating characteristic curves and the area under the curve (AUC). Meta-regression and Z-tests identified heterogeneity and compared the predictive accuracy. Subgroup analyses were performed to compare the AUC of two methods according to study type, study design, tumor size, modeling methods, and imaging modality. RESULTS: The analysis incorporated 26 studies involving 3539 patients with solitary HCC. The radiomics models showed a pooled sensitivity and specificity of 0.79 (95%CI: 0.72-0.85) and 0.78 (95%CI: 0.73-0.82), with an AUC at 0.85 (95%CI: 0.82-0.88). Conversely, the non-radiomics models had sensitivity and specificity of 0.74 (95%CI: 0.65-0.81) and 0.88 (95%CI: 0.82-0.92) and an AUC of 0.88 (95%CI: 0.85-0.91). Subgroups with preoperative MRI, larger tumors, and functional imaging had higher accuracy than those using preoperative CT, smaller tumors, and conventional imaging. CONCLUSION: Non-radiomic methods outperformed radiomic methods, but high heterogeneity calls across studies for cautious interpretation.

Efficient Electrochemical Microsensor for the Simultaneous Measurement of Hydrogen Peroxide and Ascorbic Acid in Living Brains.

Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 µM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.

Lung-specific exosomes for doxorubicin delivery in lung adenocarcinoma therapy.

Doxorubicin (DOX) could be utilized to treat lung adenocarcinoma (LUAD), while dose-limiting cardiotoxicity limits its clinical utilization. MDA-MB-231 cell-derived exosomes show lung-specific organotropism features. In this study, we aimed to explore the potential of MDA-MB-231 cell-derived exosomes in DOX specific delivery to the lung. MDA-MB-231 cell-derived exosomes were coincubated with to construct for the doxorubicin delivery system (D-EXO). Exosomes labeled with fluorescein isothiocyanate were incubated with A549 cells or 293T cells, and the engulf and the mean intensity of the fluorescence were detected with immunofluorescence and flow cytometry assay. Cell viability was detected with cell counting kit-8 (CCK-8), and cell migration was determined by scratch test. The protein expression was detected by Western blot assay. A549 cell line-derived xenograft mouse model was constructed to examine the treatment effect of D-EXO. MDA-MB-231 cell-derived exosomes could be specially taken up by A549 cells with diminished cell viability but not engulfed by 293T cells. D-EXO inhibited A549 cell migration, and upregulated the protein expression of caspase 3 and cleaved caspase 3 expression, while did not show any inhibition on 293T cells. In vivo orthotopic xenotransplantation model indicated that D-EXO inhibited tumor growth characterized by diminished tumor weight and improved survival rate. No significant change in body weight was observed after the D-EXO treatment. In conclusion, D-EXO proposed in this study could be utilized to treat LUAD with lung-specific delivery effects to improve the survival rate.

Three stilbenes from pigeon pea with promising anti-methicillin-resistant Staphylococcus aureus biofilm formation activity.

Cajaninstilbene acid (CSA), longistylin A (LLA), and longistylin C (LLC) are three characteristic stilbenes isolated from pigeon pea. The objective of this study was to evaluate the antibacterial activity of these stilbenes against Staphylococcus aureus and even methicillin-resistant Staphylococcus aureus (MRSA) and test the possibility of inhibiting biofilm formation. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these stilbenes were evaluated. And the results showed that LLA was most effective against tested strains with MIC and MBC values of 1.56 µg/mL followed by LLC with MIC and MBC values of 3.12 µg/mL and 6.25 µg/mL as well as CSA with MIC and MBC values of 6.25 µg/mL and 6.25-12.5 µg/mL. Through growth curve and cytotoxicity analysis, the concentrations of these stilbenes were determined to be set at their respective 1/4 MIC in the follow-up research. In an anti-biofilm formation assay, these stilbenes were found to be effectively inhibited bacterial proliferation, biofilm formation, and key gene expressions related to the adhesion and virulence of MRSA. It is the first time that the anti-S. aureus and MRSA activities of the three stilbenes have been systematically reported. Conclusively, these findings provide insight into the anti-MRSA mechanism of stilbenes from pigeon pea, indicating these compounds may be used as antimicrobial agents or additives for food with health functions, and contribute to the development as well as application of pigeon pea in food science.

Transgenerational hormesis and sublethal effects of five key insecticides for controlling Spodoptera frugiperda on its endoparasitoid Cotesia marginiventris.

BACKGROUND: The endoparasitoid Cotesia marginiventris (Cresson) is a promising biological control agent of the fall armyworm (FAW) Spodoptera frugiperda (Smith). Because the application of insecticides is one of the prime choices in pest management, we evaluated the sublethal and transgenerational effects of the five key insecticides-chlorantraniliprole, emamectin benzoate, spinetoram, Bacillus thuringiensis (Bt), and Mamestra brassicae nucleopolyhedrovirus (MbNPV)-on the parasitoid. RESULTS: Exposure to five insecticides at a concentration causing 10% mortality (LC10 ) caused hormetic effects in the parent generation (F0 ) by increasing the parasitism and reducing the immature duration. Interestingly, the hormetic response was also observed in the offspring generation indirectly exposed to the insecticides. Furthermore, insecticides increased the parasitism rate by 6.32-14.73% in the F1 generation, which was similar to that of the F0 generation (3.96-11.81%) compared with the control. No significant adverse effect was observed on the number of emerged parasitoids of the F1 and F2 generations. However, insecticides had a detrimental impact on body size and fecundity in the F1 and F2 generations, which showed a small body size with shorter hind tibiae and a significant reduction in the female ratio compared with the control; the exception was that chlorantraniliprole significantly improved the female ratio in the F2 generation. CONCLUSIONS: Five insecticides at LC10 induced transgenerational hormetic and sublethal effects on C. marginiventris. Our results provide a scientific basis for a better understanding of the long-term impacts of insecticides at sublethal doses on parasitoids, facilitating the development of improved integrated pest management programs for FAW control. © 2023 Society of Chemical Industry.

Genetic correlation, shared loci, but no causality between bipolar disorder and inflammatory bowel disease: A genome-wide pleiotropic analysis.

BACKGROUND AND AIMS: The comorbidity between bipolar disorder (BD) and inflammatory bowel disease (IBD) has been widely reported in observational studies. However, unclear whether this comorbidity reflects a shared genetic architecture. METHODS: Leveraging large-scale genome-wide association study (GWAS) summary statistics of BD, IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), we performed a genome-wide pleiotropic analysis to estimate heritability and genetic correlation, identify pleiotropy loci/genes, and explore the shared biological pathway. Mendelian randomization (MR) studies were subsequently employed to infer whether the potential causal relationship is present. RESULTS: We found a positive significant genetic correlation between BD and IBD (rg = 0.10, P = 7.00 × 10-4), UC (rg = 0.09, P = 2.90 × 10-3), CD (rg = 0.08, P = 6.10 × 10-3). In cross-trait meta-analysis, a total of 29, 24, and 23 independent SNPs passed the threshold for significant association between BD and IBD, UC, and CD, respectively. We identified five novel pleiotropy genes including ZDHHC2, SCRN1, INPP4B, C1orf123, and BRD3 in both BD and IBD, as well as in its subtypes UC and CD. Pathway enrichment analyses revealed that those pleiotropy genes were mainly enriched in several immune-related signal transduction pathways and cerebral disease-related pathways. MR analyses provided no evidence for a causal relationship between BD and IBD. CONCLUSION: Our findings corroborated that shared genetic basis and common biological pathways may explain the comorbidity of BD and IBD. These findings further our understanding of shared genetic mechanisms underlying BD and IBD, and potentially provide points of intervention that may allow the development of new therapies for these co-occurrent disorders.

Three new glycosides from the stems of Eurya chinensis R. Br.

Two new phenolic glycosides (1 and 2), one known analogue (3), along with a new diterpene glucoside (4) were obtained from ethanolic extract of the stems of Eurya chinensis R. Br. The structures of these isolated compounds were identified by extensive analysis of HRESIMS and NMR spectroscopic data. The cytotoxicities of these compounds were evaluated on MCF-7, A549, HepG2, CaCo2 and 5-8 F cell lines by MTT method, but no obvious activities were observed.

Soil microorganisms and methane emissions in response to short-term warming field incubation in Svalbard.

Introduction: Global warming is caused by greenhouse gases (GHGs). It has been found that the release of methane (CH4) from Arctic permafrost, soil, ocean, and sediment is closely related to microbial composition and soil factors resulting from warming over several months or years. However, it is unclear for how long continuous warming due to global warming affects the microbial composition and GHG release from soils along Arctic glacial meltwater rivers. Methods: In this study, the soil upstream of the glacial meltwater river (GR) and the estuary (GR-0) in Svalbard, with strong soil heterogeneity, was subjected to short-term field incubation at 2°C (in situ temperature), 10°C, and 20°C. The incubation was carried out under anoxic conditions and lasted for few days. Bacterial composition and CH4 production potential were determined based on high-throughput sequencing and physiochemical property measurements. Results: Our results showed no significant differences in bacterial 16S rRNA gene copy number, bacterial composition, and methanogenic potential, as measured by mcrA gene copy number and CH4 concentration, during a 7- and 13-day warming field incubation with increasing temperatures, respectively. The CH4 concentration at the GR site was higher than that at the GR-0 site, while the mcrA gene was lower at the GR site than that at the GR-0 site. Discussion: Based on the warming field incubation, our results indicate that short-term warming, which is measured in days, affects soil microbial composition and CH4 concentration less than the spatial scale, highlighting the importance of warming time in influencing CH4 release from soil. In summary, our research implied that microbial composition and CH4 emissions in soil warming do not increase in the first several days, but site specificity is more important. However, emissions will gradually increase first and then decrease as warming time increases over the long term. These results are important for understanding and exploring the GHG emission fluxes of high-latitude ecosystems under global warming.

Temperature explains intraspecific functional trait variation in Phragmites australis more effectively than soil properties.

Common reed (Phragmites australis) is a widespread grass species that exhibits a high degree of intraspecific variation for functional traits along environmental gradients. However, the mechanisms underlying intraspecific variation and adaptation strategies in response to environmental gradients on a regional scale remain poorly understood. In this study, we measured leaf, stem, and root traits of common reed in the lakeshore wetlands of the arid and semi-arid regions of the Inner Mongolia Plateau aiming to reveal the regional-scale variation for functional traits in this species, and the corresponding potentially influencing factors. Additionally, we aimed to reveal the ecological adaptation strategies of common reed in different regions using the plant economics spectrum (PES) theory. The results showed that functional-trait variation followed significant latitudinal and longitudinal patterns. Furthermore, we found that these variations are primarily driven by temperature-mediated climatic differences, such as aridity, induced by geographical distance. In contrast, soil properties and the combined effects of climate and soil had relatively minor effects on such properties. In the case of common reed, the PES theory applies to the functional traits at the organ, as well as at the whole-plant level, and different ecological adaptation strategies across arid and semi-arid regions were confirmed. The extent of utilization and assimilation of resources by this species in arid regions was a conservative one, whereas in semi-arid regions, an acquisition strategy prevailed. This study provides new insights into intraspecific variations for functional traits in common reed on a regional scale, the driving factors involved, and the ecological adaptation strategies used by the species. Moreover, it provided a theoretical foundation for wetland biodiversity conservation and ecological restoration.

Temporal and spatial patterns of habitat of Nipponia nippon in China under the background of climate change.

Crested ibis (Nipponia nippon) is one of the endangered species in the International Union for Conservation of Nature. It is of great significance to pay attention to the changes of its suitable habitat in the context of climate change. Based on the geographical distribution data of crested ibis, the MaxEnt model was used to predict the suitable habitat of crested ibis under current scenario and future climate change. The results showed that the prediction accuracy of MaxEnt model was high, with an AUC value of 0.989. The minimum temperature of the coldest month, the mean temperature of the coldest quarter, and the mean annual rainfall were the dominant environmental factors affecting the habitat of crested ibis. Under current climate scenario, the area of moderately and highly suitable area of Chinese crested ibis was 10.65×104 km2, mainly distributed in Shaanxi, Sichuan, Hubei, Henan, and Gansu. In the future, the suitable habitat area of crested ibis would increase significantly under climate change, mainly distributed in Anhui, Chongqing, Guizhou, Jiangsu, Hunan, Shandong, Shaanxi, Jiangxi, Taiwan, Yunnan, Liaoning, and Fujian. In the SSP126 scenario from 2041 to 2060, the suitable habitat area of crested ibis would reach the maximum, being 139.53×104 km2 higher than that of the current climate scenario, accounting for 19.6% of the land area. This study could provide a basis for policy making on the conservation of crested ibis under global climate change.

SLC1A5 is a novel biomarker associated with ferroptosis and the tumor microenvironment: a pancancer analysis.

Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues. Then, the relationship between SLC1A5 expression and the tumor immune microenvironment was analyzed by single-cell analysis, gene set enrichment analysis (GSEA), and Tumor Immune Estimation Resource (TIMER). Next, the correlations of the SLC1A5 expression level with immunotherapy response, immunomodulator expression, tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. Finally, in vitro experiments verified that SLC1A5 participates in ferroptosis of glioma cells to regulate tumor progression. Our results indicated that SLC1A5 is aberrantly expressed in most cancer types and closely associated with prognosis. The GSEA results showed that SLC1A5 is involved in immune activation processes and closely related to the infiltration levels of different immune cells in different cancer types. Upon further investigation, we found that SLC1A5 is a suppressor of ferroptosis in glioma, and SLC1A5 knockdown inhibited the proliferation and migration of glioma cells in vitro. In conclusion, we conducted a pancancer analysis of SLC1A5, demonstrated its role as a prognostic biomarker in cancer patients and explored its potential biological functions.

Growth of Scenedesmus obliquus on anaerobic soybean wastewater using different wasted organics for high biomass production and nutrients recycling.

The microalgae culture in mixing sewage with different characteristics may significantly improve biomass production and nutrients recycling efficiency. In this study, three waste organic wastewater including molasses, alcohol and glycerol wastewater were mixed with anaerobic soybean wastewater as mediums for microalgae culture. The optimal mixture of molasses, alcohol and glycerol wastewater was at an initial carbon-nitrogen ratio of 7:1, 5:1 and 10:1, improving biomass production by 60.4%, 31.3% and 68.7%, respectively. The removal efficiencies of organics, ammonia nitrogen and phosphorus at optimal mixture were 54.8-62.4%, 79.5-99.1% and 49.3-61.5%, and the removal rates increased by 340-630%, 27.5-66.3% and 36.3-70.2% compared to the blank culture. In addition, the culture in mixed wastewater increased lipids contrast by 0.7-1.3 times, while achieving higher saturation in fatty acids. The results suggested that microalgae culture using mixed wastewater was a strategy for high biomass production and nutrients recycling efficiency.

Four new stilbenes and one new flavonoid with potential antibacterial and anti-SARS-CoV-2 activity from Cajanus cajan.

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity.

The sesquiterpenes with the COVID-19 Mpro inhibitory activity from the Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded four new sesquiterpenes including a novel skeleton (claroguaiane A, 1), two guaianolides (claroguaianes B-C, 2-3), and one eudesmanolide (claroeudesmane A, 4), together with three known sesquiterpenoids (5-7). The structures of the new compounds were elucidated by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitive activity of COVID-19 Mpro. As a result, compound 5 showed moderate activity with an IC50 value of 36.81 µM and compound 6 exhibited a potent inhibitory effect with an IC50 value of 16.58 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

SiO2/hyaluronic acid nanoparticles carry CaO2, DOX and p53 plasmid to effectively achieve ion interference/chemical/gene multimodal therapy of lung cancer.

Monotherapy of lung cancer shows limited therapeutic effects due to its poorly targeted enrichment and low bioavailability. Using nanomaterials as carriers to form drug delivery systems has become a popular method to improve the targeting of anticancer drug therapy and patients' safety. However, the uniformity of the loaded drugs and the unsatisfactory effects are still the bottleneck in this field up to now. This study aims to construct a novel nanocomposite carrying 3 different types of anticancer drugs to enhance treatment efficacy. Herein, mesoporous silica (MSN) with high loading rate was constructed by dilute sulfuric acid thermal etching as the framework. Hyaluronic acid (HA) was loaded with CaO2, p53 and DOX to construct nanoparticle complexes-SiO2@CaO2@DOX@P53-HA. First, MSN was proved to be a porous sorbent with a mesoporous structure through BET analysis. The images obtained from the uptake experiment clearly show the gradual enrichment of the DOX and Ca2+ within the target cell. For in vitro experiments, the pro-apoptotic effects of SiO2@CaO2@DOX@P53-HA significantly increased compared to that of the single-agent group at different time points. Furthermore, in the tumor-bearing mouse experiment, the tumor volume was remarkably inhibited in the SiO2@CaO2@DOX@P53-HA group compared to that in the single-agent group. By observing the pathological sections of the euthanized mice, it is obvious that the tissues of the mice treated with the nanoparticles were more intact. Based on these beneficial results, it is believed that multimodal therapy is a meaningful treatment strategy for lung cancer.