Achieving Tunable Mechanoluminescence in CaZnOS:Tb3+, Sm3+ for Multicolor Stress Sensing.

Mechanoluminescent (ML) materials can exhibit visible-to-near-infrared mechanoluminescence when responding to the fracture or deformation of a solid under mechanical stimulation. Transforming mechanical energy into light demonstrates promising applications in terms of visual mechanical sensing. In this work, we synthesized the phosphor CaZnOS:Tb3+, Sm3+, which exhibited intense and tunable multicolor mechanoluminescence without pre-irradiation. Intense green ML materials were obtained by doping Tb3+ with different concentrations. Tunable multicolor mechanoluminescence (such as green, yellow-green, and orange-red) could be realized by combining green emission (about 542 nm), attributed to Tb3+, and red emission (about 600 nm) generated from the Sm3+ in the CaZnOS substrate. The tunable multicolor ML materials CaZnOS:Tb3+, Sm3+ exhibited intense luminance and recoverable mechanoluminescence when responding to mechanical stimulation. Benefiting from the excellent ML performance and multicolor tunability in CaZnOS:Tb3+, Sm3+, we mixed the phosphor with PDMS and a curing agent to explore its practical application. An application for visual mechanical sensing was designed for handwriting identification. By taking a time-lapsed shot while writing, we easily obtained images of the writer's handwriting. The images of the ML intensity were acquired by using specific software to transform the shooting data. We could easily distinguish people's handwriting through analyzing the different ML performances.

Circadian rhythm sleep loss impairs motor inhibition more than motor execution in continuous action.

Under total sleep deprivation, both inhibitory and motor control are impaired. However, how circadian rhythm sleep loss caused by irregular sleep pattern affects motor inhibition and execution in continuous actions remains unknown. This study utilized a pointing task to investigate the question over 30 days. During regular trials, participants were instructed to tap on a specified location, while in countermanding trials, they were required to countermand their current action. Additionally, there was a control group performed the same task following a normal 24-h rhythm. The results indicated that the decrease in accuracy and the increase in movement time in countermanding trials were more prominent in the shift work group. In contrast, there was no significant difference in reaction time between the two groups. Notably, the shift work group outperformed the control group in terms of movement time in regular trials and radial displacement in countermanding trials. Overall, these results show that circadian rhythm sleep loss predominantly affects inhibitory control, rather than motor control, underscoring the nuanced impacts of sleep disruption on differential aspects of cognitive and motor functions.

Air-Stable Wafer-Scale Ferromagnetic Metallo-Carbon Nitride Monolayer.

The pursuit of robust, long-range magnetic ordering in two-dimensional (2D) materials holds immense promise for driving technological advances. However, achieving this goal remains a grand challenge due to enhanced quantum and thermal fluctuations as well as chemical instability in the 2D limit. While magnetic ordering has been realized in atomically thin flakes of transition metal chalcogenides and metal halides, these materials often suffer from air instability. In contrast, 2D carbon-based materials are stable enough, yet the challenge lies in creating a high density of local magnetic moments and controlling their long-range magnetic ordering. Here, we report a novel wafer-scale synthesis of an air-stable metallo-carbon nitride monolayer (MCN, denoted as MN4/CNx), featuring ultradense single magnetic atoms and exhibiting robust room-temperature ferromagnetism. Under low-pressure chemical vapor deposition conditions, thermal dehydrogenation and polymerization of metal phthalocyanine (MPc) on copper foil at elevated temperature generate a substantial number of nitrogen coordination sites for anchoring magnetic single atoms in monolayer MN4/CNx (where M = Fe, Co, and Ni). The incorporation of densely populating MN4 sites into monolayer MCN networks leads to robust ferromagnetism up to room temperature, enabling the observation of anomalous Hall effects with excellent chemical stability. Detailed electronic structure calculations indicate that the presence of high-density metal sites results in the emergence of spin-split d-bands near the Fermi level, causing a favorable long-range ferromagnetic exchange coupling through direct exchange interactions. Our work demonstrates a novel synthesis approach for wafer-scale MCN monolayers with robust room-temperature ferromagnetism and may shed light on practical electronic and spintronic applications.

Lysosomal-Associated Protein Transmembrane 5, Tubular Senescence, and Progression of CKD.

BACKGROUND: Tubular senescence is a major determinant of chronic kidney disease (CKD) and identification of potential therapeutic targets involved in senescent tubular epithelial cells has clinical importance. Lysosomal-associated protein transmembrane 5 (LAPTM5) is a key molecule related to T and B cell receptor expression and inflammation. However, the expression pattern of LAPTM5 in the kidney and the contribution of LAPTM5 to the development of CKD keep unknown. METHODS: LAPTM5-/- mice and tubule specific-LAPTM5 knockout mice were used to examine the role of LAPTM5 in tubular senescence by establishing different experimental mouse CKD models. RESULTS: LAPTM5 expression was significantly induced in the kidney, especially in proximal tubules and distal convoluted tubules, from mice with aristolochic acid nephropathy, bilateral ischemia/reperfusion injury (IRI)-induced CKD or unilateral ureter obstruction (UUO). Tubule-specific deletion of LAPTM5 inhibited senescence of tubular epithelial cells and alleviated tubulointerstitial fibrosis in aged mice. Moreover, LAPTM5 deficiency ameliorated kidney injury and tubular senescence in mice with CKD. Mechanistically, LAPTM5 inhibited ubiquitination of NICD1 by mediating WWP2 lysosomal degradation, then leading to cellular senescence in tubular epithelial cells. Notably, we also observed a higher expression of LAPTM5 in tubules from individuals with CKD and the level of LAPTM5 was correlated with kidney fibrosis and tubular senescence in people with CKD. CONCLUSIONS: LAPTM5 contributed to tubular senescence by regulating WWP2/NICD1 signaling pathway and exacerbated kidney injury during the progression of CKD.

Functionalized xanthohumol nanoemulsion: fabrication, characterization and bioavailability enhancement of bioactive compounds.

BACKGROUND: Xanthohumol is an isopentadienyl flavonoid in hops, which have several pharmacological effects. However, due to the poor bioavailability of xanthohumol, it cannot be widely used. RESULT: In this study, solvent extraction combined with preparative liquid chromatography was used to separate and purify xanthohumol in hop residue. And the purity, yield and recovery of xanthohumol was 983.0 ± 2.1 g kg-1, 921.61 ± 5.65 g kg-1, and 5.41 ± 0.07 g kg-1, respectively. Response surface methodology optimization revealed that 216.75 g kg-1 ethyl oleate, 574.1 g kg-1 polyoxyl-35 castor oil (EL35) and 209.15 g kg-1 polyethylene glycol 200 (PEG200) produced the xanthohumol nanoemulsion with a loading capacity of 85.40 ± 0.33 g kg-1, mean droplet diameter of 42.35 ± 0.06 nm, and zeta potential of -21.78 ± 0.18 mV. CONCLUSION: Xanthohumol nanoemulsion has better relative stability. The relative oral bioavailability of xanthohumol nanoemulsion was increased by 1.76 times. These results provide a theoretical basis for the application of nanoemulsion containing xanthohumol in food and pharmaceutical industry. © 2024 Society of Chemical Industry.

Exploring the effects of environmentally relevant concentrations of tris(2-chloroethyl) phosphate on tadpole health: A comprehensive analysis of intestinal microbiota and hepatic transcriptome.

Tris(2-chloroethyl) phosphate (TCEP), a chlorinated organophosphate ester, is commonly found in aquatic environments. Due to its various toxic effects, it may pose a risk to the health of aquatic organisms. However, the potential impacts of TCEP exposure on the intestinal microbiota and hepatic function in amphibians have not been reported. This study investigated the impact of long-term exposure to environmentally relevant concentrations of TCEP (0, 3, and 90 µg/L) on the intestinal microbiota and hepatic transcriptome of Polypedates megacephalus tadpoles. The results showed that the body size of the tadpoles decreased significantly with an increase in TCEP concentration. Additionally, TCEP exposure affected the diversity and composition of the intestinal microbiota in tadpoles, leading to significant changes in the relative abundance of certain bacterial groups (the genera Aeromonas decreased and Citrobacter increased) and potentially promoting a more even distribution of microbial species, as indicated by a significant increase in the Simpson index. Moreover, the impact of TCEP on hepatic gene expression profiles in tadpoles was significant, with the majority of differentially expressed genes (DEGs) (709 out of 906 total DEGs in 3 µg/L of TCEP versus control, and 344 out of 387 DEGs in 90 µg/L of TCEP versus control) being significantly down-regulated, which were primarily related to immune response and immune system process. Notably, exposure to TCEP significantly reduced the relative abundance of the genera Aeromonas and Cetobacterium in the tadpole intestine. This reduction was positively correlated with the down-regulated expression of immune-related genes in the liver of corresponding tadpoles. In summary, these findings provide empirical evidence of the potential health risks to tadpoles exposed to TCEP at environmentally relevant concentrations.

Structural insights into the binding of nanobodies to the Staphylococcal enterotoxin B.

Staphylococcal Enterotoxin Type B (SEB), produced by Staphylococcus aureus bacteria, is notorious for inducing severe food poisoning and toxic shock syndrome. While nanobody-based treatments hold promises for combating SEB-induced diseases, the lack of structural information between SEB and nanobodies has hindered the development of nanobody-based therapeutics. Here, we present crystal structures of SEB-Nb3, SEB-Nb6, SEB-Nb8, SEB-Nb11, and SEB-Nb20 at resolutions ranging from 1.59 Å to 2.33 Å. Crystallographic analysis revealed that Nb3, Nb8, Nb11, and Nb20 bind to SEB at the T-cell receptor (TCR) interface, while Nb6 binds at the major histocompatibility complex (MHC) interface, suggesting their potential to inhibit SEB function by disrupting interactions with TCR or MHC molecules. Molecular biological analyses confirmed the thermodynamic and kinetic parameters of Nb3, Nb5, Nb6, Nb8, Nb11, Nb15, Nb18, and Nb20 to SEB. The competitive inhibition was further confirmed by cell-based experiments demonstrating nanobody neutralization. These findings elucidate the structural basis for developing specific nanobodies to neutralize SEB threats, providing crucial insights into the underlying mechanisms and offering significant assistance for further optimization towards future therapeutic strategies.

Integrated biomarker-based ecological risks assessment of tadpole responses to tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, and their combined environmental exposure.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCPP) are common chlorinated organophosphorus flame retardants (OPFRs) used in industry. They have been frequently detected together in aquatic environments and associated with various hazardous effects. However, the ecological risks of prolonged exposure to these OPFRs at environmentally relevant concentrations in non-model aquatic organisms remain unexplored. This study investigated the effects of long-term exposure (up to 25 days) to TCEP and TCPP on metamorphosis, hepatic antioxidants, and endocrine function in Polypedates megacephalus tadpoles. Exposure concentrations were set at 3, 30, and 90 µg/L for each substance, conducted independently and in equal-concentration combinations, with a control group included for comparison. The integrated biomarker response (IBR) method developed an optimal linear model for predicting the overall ecological risks of TCEP and TCPP to tadpoles in potential distribution areas of Polypedates species. Results showed that: (1) Exposure to environmentally relevant concentrations of TCEP and TCPP elicited variable adverse effects on tadpole metamorphosis time, hepatic antioxidant enzyme activity and related gene expression, and endocrine-related gene expression, with their combined exposure exacerbating these effects. (2) The IBR value of TCEP was consistently greater than that of TCPP at each concentration, with an additive effect observed under their combined exposure. (3) The ecological risk of tadpoles exposed to the combined presence of TCEP and TCPP was highest in China's Taihu Lake and Vietnam's Hanoi than in other distribution locations. In summary, prolonged exposure to environmentally relevant concentrations of TCEP and TCPP presents potential ecological risks to amphibian tadpoles, offering insights for the development of policies and strategies to control TCEP and TCPP pollution in aquatic ecosystems. Furthermore, the methodology employed in establishing the IBR prediction model provides a methodological framework for assessing the overall ecological risks of multiple OPFRs.

Distinct fungal communities affecting opposite galanthamine accumulation patterns in two Lycoris species.

Lycoris radiata is the main source of galanthamine, a clinical drug used in Alzheimer's disease; however, the galanthamine content in L. radiata is low. Lycoris aurea is another Lycoris species with high galanthamine content. Fungal endophytes can enhance plant secondary metabolite accumulation; thus, we compared the fungal communities in these two Lycoris species to identify certain fungal taxa in L. aurea capable of enhancing galanthamine accumulation. Several fungal endophytes, which were enriched in, exclusively isolated from L. aurea, or showed significant correlations with galanthamine, were demonstrated to enhance the accumulation of only galanthamine but no other Amaryllidaceae alkaloids (AAs) in L. radiata. These fungal endophytes mainly upregulated the downstream genes in the biosynthesis pathways of AAs in L. radiata, suggesting that they may allocate more precursors for galanthamine biosynthesis. This study demonstrated that fungal endophytes from L. aurea with higher galanthamine content can specifically enhance the accumulation of this medicinal alkaloid in other Lycoris species, thereby increasing the galanthamine source and reducing galanthamine separation and purification costs. This study broadens our understanding of the complex interactions between plant secondary metabolites and fungal endophytes.

A Cross Talking between the Gut Microbiota and Metabolites of Participants in a Confined Environment.

Certain workplaces, like deep-sea voyages, subject workers to chronic psychological stress and circadian rhythm disorders due to confined environments and frequent shifts. In this study, participants lived in a strictly controlled confined environment, and we analyzed the effects of a confined environment on gut microbiota and metabolites. The results showed that living in confined environments can significantly alter both the gut microbiota and the gut metabolome, particularly affecting lipid metabolism pathways like glycerophospholipid metabolism. There was a significant reduction in the abundance of Faecalibacterium and Bacteroides, while Blautia, Bifidobacterium, and Collinsella showed significant increases. An association analysis revealed a strong correlation between changes in the gut microbiota and the metabolome. Four upregulated lipid metabolites may serve as biomarkers for damage induced by confined environments, and certain gut microbiota alterations, such as those involving Faecalibacterium and Bacteroides, could be potential psychobiotics or therapeutic targets for enhancing mental health in a confined environment.

Parallel degradome-seq and DMS-MaPseq substantially revise the miRNA biogenesis atlas in Arabidopsis.

MicroRNAs (miRNAs) are produced from highly structured primary transcripts (pri-miRNAs) and regulate numerous biological processes in eukaryotes. Due to the extreme heterogeneity of these structures, the initial processing sites of plant pri-miRNAs and the structural rules that determine their processing have been predicted for many miRNAs but remain elusive for others. Here we used semi-active DCL1 mutants and advanced degradome-sequencing strategies to accurately identify the initial processing sites for 147 of 326 previously annotated Arabidopsis miRNAs and to illustrate their associated pri-miRNA cleavage patterns. Elucidating the in vivo RNA secondary structures of 73 pri-miRNAs revealed that about 95% of them differ from in silico predictions, and that the revised structures offer clearer interpretation of the processing sites and patterns. Finally, DCL1 partners Serrate and HYL1 could synergistically and independently impact processing patterns and in vivo RNA secondary structures of pri-miRNAs. Together, our work sheds light on the precise processing mechanisms of plant pri-miRNAs.

Toxicity comparison and risk assessment of two chlorinated organophosphate flame retardants (TCEP and TCPP) on Polypedates megacephalus tadpoles.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1­chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 µg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments.

[Determination of fatty acid composition after saponification of common oil pharmaceutical excipients by supercritical fluid-evaporative light scattering method and its application in oil identification].

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.

On-site analysis and rapid identification of citrus herbs by miniature mass spectrometry and machine learning.

BACKGROUND: Natural medicines present a considerable analytical challenge due to their diverse botanical origins and complex multi-species composition. This inherent complexity complicates their rapid identification and analysis. Tangerine peel, a product of the Citrus species from the Rutaceae family, is widely used both as a culinary ingredient and in traditional Chinese medicine. It is classified into two primary types in China: Citri Reticulatae Pericarpium (CP) and Citri Reticulatae Pericarpium Viride (QP), differentiated by harvest time. A notable price disparity exists between CP and another variety, Citri reticulatae "Chachi" (GCP), with differences being based on the original variety. METHODS: This study introduces an innovative method using portable miniature mass spectrometry for swift on-site analysis of QP, CP, and GCP, requiring less than a minute per sample. And combined with machine learning to differentiate the three types on site, the method was used to try to distinguish GCP from different storage years. RESULTS: This novel method using portable miniature mass spectrometry for swift on-site analysis of tangerine peels enabled the characterization of 22 compounds in less than one minute per sample. The method simplifies sample processing and integrates machine learning to distinguish between the CP, QP, and GCP varieties. Moreover, a multiple-perceptron neural network model is further employed to specifically differentiate between CP and GCP, addressing the significant price gap between them. CONCLUSIONS: The entire analytical time of the method is about 1 minute, and samples can be analyzed on site, greatly reducing the cost of testing. Besides, this approach is versatile, operates independently of location and environmental conditions, and offers a valuable tool for assessing the quality of natural medicines.

Effects of aeolian deposition on soil properties and microbial carbon metabolism function in farmland of Songnen Plain, China.

The effects of wind erosion, one of the crucial causes of soil desertification in the world, on the terrestrial ecosystem are well known. However, ecosystem responses regarding soil microbial carbon metabolism to sand deposition caused by wind erosion, a crucial driver of biogeochemical cycles, remain largely unclear. In this study, we collected soil samples from typical aeolian deposition farmland in the Songnen Plain of China to evaluate the effects of sand deposition on soil properties, microbial communities, and carbon metabolism function. We also determined the reads number of carbon metabolism-related genes by high-throughput sequencing technologies and evaluated the association between sand deposition and them. The results showed that long-term sand deposition resulted in soil infertile, roughness, and dryness. The impacts of sand deposition on topsoil were more severe than on deep soil. The diversity of soil microbial communities was significantly reduced due to sand deposition. The relative abundances of Nitrobacteraceae, Burkholderiaceae, and Rhodanobacteraceae belonging to α-Proteobacteria significantly decreased, while the relative abundances of Streptomycetaceae and Geodermatophilaceae belonging to Actinobacteria increased. The results of the metagenomic analysis showed that the gene abundances of carbohydrate metabolism and carbohydrate-activity enzyme (GH and CBM) significantly decreased with the increase of sand deposition amount. The changes in soil microbial community structure and carbon metabolism decreased soil carbon emissions and carbon cycling in aeolian deposition farmland, which may be the essential reasons for land degradation in aeolian deposition farmland.

Borneol acts as an adjuvant agent to enhance the oral absorption of Panax notoginseng saponins in rats: Effect of optical configuration and compatibility ratios.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng, shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. AIM OF THE STUDY: This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. MATERIALS AND METHODS: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. RESULTS: The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d-borneol (DB), l-borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. CONCLUSIONS: This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO.

A versatile economic strategy by HPLC-CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations.

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

Nomogram model for predicting cancer-specific mortality in patients with early-onset colorectal cancer: a competing risk analysis insight from the SEER database and an external validation cohort.

Background: Early-onset colorectal cancer (EOCRC) is increasing in incidence and poses a growing threat. Urgent research is needed, especially in survival analysis, to enhance comprehension and treatment strategies. This study aimed to explore the risk factors associated with cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with EOCRC. Additionally, the study aimed to develop a nomogram predicting CSM using a competitive risk model and validate its accuracy through the use of training, using internal and external cohorts. Methods: Data from EOCRC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017). EOCRC patients who were treated at a tertiary hospital in northeast China between 2014 and 2020 were also included in the study. The SEER data were divided into the training and validation sets at a 7:3 ratio. A univariate Cox regression model was employed to identify prognostic factors. Subsequently, multivariate Cox regression models were applied to ascertain the presence of independent risk factors. A nomogram was generated to visualize the results, which were evaluated using the concordance index (C-index), area under the curve (AUC), and calibration curves. The clinical utility was assessed via decision curve analysis (DCA). Results: Multivariable Cox regression analysis demonstrated that factors such as race, tumor differentiation, levels of carcinoembryonic antigen (CEA), marital status, histological type, American Joint Committee on Cancer (AJCC) stage, and surgical status were independent risk factors for CSM in EOCRC patients. In addition, age, gender, chemotherapy details, CEA levels, marital status, and AJCC stage were established as independent risk factors for OCM in individuals diagnosed with EOCRC. A nomogram was developed using the identified independent risk factors, demonstrating excellent performance with a C-index of 0.806, 0.801, and 0.810 for the training, internal validation, and external validation cohorts, respectively. The calibration curves and AUC further confirmed the accuracy and discriminative ability of the nomogram. Furthermore, the DCA results indicated that the model had good clinical value. Conclusions: In this study, a competing risk model for CSM was developed in EOCRC patients. The model demonstrates a high level of predictive accuracy, providing valuable insights into the treatment decision-making process.

P53 upregulation by USP7-engaging molecular glues.

Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53. P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases, whereas deubiquitinases (DUBs) remove polyubiquitination conjugates to counteract these E3 ligases. Thus, small-molecular glues that enhance P53 anchoring to DUBs may stabilize P53 through deubiquitination. Here, using small-molecule microarray-based technology and unbiased screening, we identified three potential molecular glues that may tether P53 to the DUB, USP7, and elevate the P53 level. Among the molecular glues, bromocriptine (BC) is an FDA-approved drug with the most robust effects. BC was further verified to increase P53 stability via the predicted molecular glue mechanism engaging USP7. Consistent with P53 upregulation in cancer cells, BC was shown to inhibit the proliferation of cancer cells in vitro and suppress tumor growth in a xenograft model. In summary, we established a potential screening platform and identified potential molecular glues upregulating P53. Similar strategies could be applied to the identification of other types of molecular glues that may benefit drug discovery and chemical biology studies.

Biological and physiological effects in Bemisia tabaci feeding on tomatoes endophytically colonized by Beauveria bassiana.

BACKGROUND: Entomopathogenic fungi (EPF) treatment of plants may affect the survival and feeding preferences of herbivorous pests. However, comprehensive studies on the fitness across their entire life cycle, feeding behavior, and physiological changes in herbivores consuming EPF-treated plants within the tripartite interactions of EPF, plants, and pests are still limited. In this study, we utilized life tables, electrical penetration graph (EPG), and metabolomics to uncover the biological and physiological characteristics of Bemisia tabaci on tomato plants inoculated with Beauveria bassiana through root irrigation. RESULTS: Our study indicated that Beauveria bassiana Bb252 can penetrate the entire tissue from the point of inoculation, primarily colonizing the intercellular spaces and vascular tissue. However, this colonization is temporary, lasting no more than 35 days. Moreover, the population fitness and feeding behavior of Bemisia tabaci on tomato plants treated with Beauveria bassiana via root irrigation were significantly affected, showing a substantial 41.4% decrease in net reproductive rate (R0), a notable reduction in watery salivation, and shortened phloem ingestion. Lastly, we observed a significant decrease in hormones and amino acids of whiteflies that fed on Beauveria bassiana-treated tomato plants by root irrigation. CONCLUSIONS: Our results indicated that the endophyte, Beauveria bassiana Bb252, reduced demographic fitness of Bemisia tabaci by altering its hormones and amino acids levels. These findings enhance our understanding of multitrophic interactions in integrated pest management. © 2024 Society of Chemical Industry.