Evaluation of deep eutectic solvents chiral selectors based on lactobionic acid in capillary electrophoresis.

Recently, deep eutectic solvents (DESs) have attracted considerable interest in analytical chemistry. This work described the enantioseparations of twenty amino alcohol drugs with several DESs based on lactobionic acid (LA) as the sole chiral selector in capillary electrophoresis (CE) firstly. Compared to the single LA system and the ionic liquid/LA synergistic system, the DES system exhibited considerably improved separations. The influences of some key parameters on separations were investigated in detail. This work also experimentally demonstrated that the carboxyl group was indispensable in the process of chiral recognition. The mechanisms of the improvements of DESs on enantioseparations were studied via ultraviolet spectroscopy. Furthermore, the proposed method was used to determine the enantiomeric purity of propranolol hydrochloride successfully. This is the first time that chiral DESs were utilized as the sole chiral selectors in CE, and this strategy has opened up a new prospect for the use of DESs in enantioseparation.

Amino acids-based deep eutectic solvents as additives for improved enantioseparation in capillary electrophoresis.

In this study, several amino acids deep eutectic solvents were prepared using L-valine and L-leucine as hydrogen bond acceptors, and L-lactic acid and glycerol as hydrogen bond donors. These amino acids' deep eutectic solvents were first used as buffer additives to construct several synergistic systems along with maltodextrin in capillary electrophoresis for the enantioseparations of four racemic drugs. Compared with single maltodextrin system, the separations of model drugs in the synergistic systems were significantly improved. Some key parameters affecting chiral separation such as maltodextrin concentration, deep eutectic solvent concentration, buffer pH, and applied voltage were optimized. In order to further understand the specific mechanism of the amino acids deep eutectic solvents in improving chiral separation, we first calculated the binding constants of maltodextrin with enantiomers using the capillary electrophoresis method in the two separation modes, respectively. We also used molecular simulation to calculate the binding free energy of maltodextrin with enantiomers. It is the first time that amino acids deep eutectic solvents were used for enantioseparation in capillary electrophoresis, which will greatly promote the development of deep eutectic solvents in the field of chiral separation.

Investigation on improvement of enantioseparation based on clindamycin phosphate by chiral deep eutectic solvents in capillary electrophoresis.

In this work, the potential synergetic effect between deep eutectic solvents and an antibiotic chiral selector (clindamycin phosphate) for enantioseparation was investigated in capillary electrophoresis. We synthesized a series of deep eutectic solvents with choline chloride as hydrogen bond acceptor and three α-hydroxyl acids (l-lactic acid, l-malic acid, and l-tartaric acid) as hydrogen bond donors. Compared to the single clindamycin phosphate separation system, significantly improved separations of model drugs were observed in several synergetic systems. Compared to deep eutectic solvents with a single hydrogen bond donor, deep eutectic solvents with mixed-type hydrogen bond donors were superior. The influences of several key parameters including the type and proportion of organic modifier, clindamycin phosphate concentrations, deep eutectic solvents concentrations, and buffer pH were investigated in detail. The mechanism of the enhanced separations in deep eutectic solvents systems was investigated by means of electroosmotic flow analysis, nuclear magnetic resonance analysis, and molecular modeling. It was the first time that the synergetic systems between deep eutectic solvents and antibiotic chiral selector were established in capillary electrophoresis, and these deep eutectic solvents were demonstrated to have a good synergetic effect with clindamycin phosphate for enantioseparation.

The MADS-box transcription factor GmFULc promotes GmZTL4 gene transcription to modulate maturity in soybean.

Flowering time and maturity are crucial agronomic traits that affect the regional adaptability of soybean plants. The development of soybean cultivars with early maturity adapted to longer days and colder climates of high latitudes is very important for ensuring normal ripening before frost begins. FUL belongs to the MADS-box transcription factor family and has several duplicated members in soybeans. In this study, we observed that overexpression of GmFULc in the Dongnong 50 cultivar promoted soybean maturity, while GmFULc knockout mutants exhibited late maturity. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that GmFULc could bind to the CArG, bHLH and homeobox motifs. Further investigation revealed that GmFULc could directly bind to the CArG motif in the promoters of the GmZTL3 and GmZTL4 genes. Overexpression of GmZTL4 promoted soybean maturity, whereas the ztl4 mutants exhibited delayed maturity. Moreover, we found that the cis element box 4 motif of the GmZTL4 promoter, a motif of light response elements, played an important role in controlling the growth period. Deletion of this motif shortened the growth period by increasing the expression levels of GmZTL4. Functional investigations revealed that short-day treatment promoted the binding of GmFULc to the promoter of GmZTL4 and inhibited the expression of E1 and E1Lb, ultimately resulting in the promotion of flowering and early maturation. Taken together, these findings suggest a novel photoperiod regulatory pathway in which GmFULc directly activates GmZTL4 to promote earlier maturity in soybean.

PWSC: a novel clustering method based on polynomial weight-adjusted sparse clustering for sparse biomedical data and its application in cancer subtyping.

BACKGROUND: Clustering analysis is widely used to interpret biomedical data and uncover new knowledge and patterns. However, conventional clustering methods are not effective when dealing with sparse biomedical data. To overcome this limitation, we propose a hierarchical clustering method called polynomial weight-adjusted sparse clustering (PWSC). RESULTS: The PWSC algorithm adjusts feature weights using a polynomial function, redefines the distances between samples, and performs hierarchical clustering analysis based on these adjusted distances. Additionally, we incorporate a consensus clustering approach to determine the optimal number of classifications. This consensus approach utilizes relative change in the cumulative distribution function to identify the best number of clusters, resulting in more stable clustering results. Leveraging the PWSC algorithm, we successfully classified a cohort of gastric cancer patients, enabling categorization of patients carrying different types of altered genes. Further evaluation using Entropy showed a significant improvement (p = 2.905e-05), while using the Calinski-Harabasz index demonstrates a remarkable 100% improvement in the quality of the best classification compared to conventional algorithms. Similarly, significantly increased entropy (p = 0.0336) and comparable CHI, were observed when classifying another colorectal cancer cohort with microbial abundance. The above attempts in cancer subtyping demonstrate that PWSC is highly applicable to different types of biomedical data. To facilitate its application, we have developed a user-friendly tool that implements the PWSC algorithm, which canbe accessed at http://pwsc.aiyimed.com/ . CONCLUSIONS: PWSC addresses the limitations of conventional approaches when clustering sparse biomedical data. By adjusting feature weights and employing consensus clustering, we achieve improved clustering results compared to conventional methods. The PWSC algorithm provides a valuable tool for researchers in the field, enabling more accurate and stable clustering analysis. Its application can enhance our understanding of complex biological systems and contribute to advancements in various biomedical disciplines.

Rigidity-Dependent Emission: Inspired Selection of an ATP-Specific Polyvalent Hydrogen Binding-Lighted Fluorophore for Intracellular Amplified Imaging.

ATP, a small molecule with high intracellular concentration (mM level), provides a fuel to power signal amplification, which is meaningful for biosensing. However, traditional ATP-powered amplification is based on ATP/aptamer recognition, which is susceptible to the complex biological microenvironment (e.g., nuclease). In this work, we communicate a signaling manner termed as ATP-specific polyvalent hydrogen binding (APHB), which is mimetic to ATP/aptamer binding but can avoid interference from biomolecules. The key in APHB is a functional fluorophore that can selectively bind with ATP via polyvalent hydrogen, and the fluorescence was lighted with the changes of the molecular structure from flexibility to rigidity. By designing, synthesizing, and screening a series of compounds, we successfully obtained an ATP-specific binding-lighted fluorophore (ABF). Experimental verification and a complex analogue demonstrated that two melamine brackets in the ABF dominate the polyvalent hydrogen binding between the ABF and ATP. Then, to achieve amplification biosensing, fibroblast activation protein (FAP) in activated hepatic stellate cells was taken as a model target, and a nanobeacon consisting of an ABF, a quencher, and an FAP-activated polymer shell was constructed. Benefiting from the ATP-powered amplification, the FAP was sensitively detected and imaged, and the potential relationship between differentiation of hepatocytes and FAP concentration was first revealed, highlighting the great potential of APHB-mediated signaling for intracellular sensing.

A novel TF molecular switch-mechanism found in two contrasting ecotypes of a psammophyte, Agriophyllum squarrosum, in regulating transcriptional drought memory.

BACKGROUND: Prior drought stress may change plants response patterns and subsequently increase their tolerance to the same condition, which can be referred to as "drought memory" and proved essential for plants well-being. However, the mechanism of transcriptional drought memory in psammophytes remains unclear. Agriophyllum squarrosum, a pioneer species on mobile dunes, is widely spread in Northern China's vast desert areas with outstanding ability of water use efficiency. Here we conducted dehydration-rehydration treatment on A. squarrosum semi-arid land ecotype AEX and arid land ecotype WW to dissect the drought memory mechanism of A. squarrosum, and to determine the discrepancy in drought memory of two contrasting ecotypes that had long adapted to water heterogeneity. RESULT: Physiological traits monitoring unveiled the stronger ability and longer duration in drought memory of WW than that of AEX. A total of 1,642 and 1,339 drought memory genes (DMGs) were identified in ecotype AEX and WW, respectively. Furthermore, shared DMGs among A. squarrosum and the previously studied species depicted that drought memory commonalities in higher plants embraced pathways like primary and secondary metabolisms; while drought memory characteristics in A. squarrosum were mainly related to response to heat, high light intensity, hydrogen peroxide, and dehydration, which might be due to local adaptation to desert circumstances. Heat shock proteins (HSPs) occupied the center of the protein-protein interaction (PPI) network in drought memory transcription factors (TF), thus playing a key regulatory role in A. squarrosum drought memory. Co-expression analysis of drought memory TFs and DMGs uncovered a novel regulating module, whereby pairs of TFs might function as molecular switches in regulating DMG transforming between high and low expression levels, thus promoting drought memory reset. CONCLUSION: Based on the co-expression analysis, protein-protein interaction prediction, and drought memory metabolic network construction, a novel regulatory module of transcriptional drought memory in A. squarrosum was hypothesized here, whereby recurrent drought signal is activated by primary TF switches, then amplified by secondary amplifiers, and thus regulates downstream complicated metabolic networks. The present research provided valuable molecular resources on plants' stress-resistance basis and shed light on drought memory in A. squarrosum.

Evaluation of kasugamycin as a chiral selector in capillary electrophoresis.

The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in capillary electrophoresis (CE) for six pairs of stereoisomers, including ephedrine and pseudoephedrine, quinine and quinidine, cinchonine and cinchonidine, and amlodipine, promethazine and ofloxacin enantiomers. Kasugamycin, an aminoglycoside antibiotic in agriculture, shows significant biological activity against rice blast with low toxicity. As it turns out, this new chiral selector possesses good CE compatibility and stereoselectivity towards model analytes. In this work, we systematically investigated several separation parameters including kasugamycin concentration, buffer pH, separation voltage and the composition of the buffer solution. A detailed discussion about the chiral recognition mechanism was made based on Statistical Product and Service Solution (SPSS) analysis, NMR experiments (1D and 2D) and molecular modeling. This is the first time that kasugamycin is utilized as a chiral selector in CE, and the development of new chiral selectors from agricultural or veterinary antibiotics deserves more attention.

Investigation of the chiral recognition role of cyclodextrin hydroxyl moieties via high performance liquid chromatography.

Cyclodextrin (CD) is known to afford excellent enantioselectivities due to its hydrophobic cavity and external H-bonding sites from hydroxyl moieties. However, there is still a lack of direct and comprehensive evidence clearly illustrating the origin of the important H-bonding effect. Regarding this issue, herein, four allylimidazole CD derivatives by selective substitution of the primary (6-position) and/or secondary (2,3-position) CD were synthesized and clicked onto silica surfaces to afford the corresponding chiral stationary phases (CSPs). The chiral chromatographic performances were systematically evaluated by separating 35 racemic analytes including isoxazolines, dansyl-amino acids, flavonoids and other racemates under reversed-phase HPLC. The chiral selection factors (α) and retention times (k) of the analytes on the as-prepared CSPs were comprehensively compared and it reveals that the enantioseparation ability was significantly altered due to the selective substituents of CD hydroxyl groups. The natural allylimidazole CD CSP (AICDCSP) was superior to the 6-O-tert-butyldimethylsilyl AICDCSP (6-TBDMAICDCSP) for most analytes. Dansyl amino acids and Ar-Pys were well separated on AICDCSP and 6-TBDMAICDCSP, where dansyl amino leucine gained the highest resolution up to 4.72 on AICDCSP, and flavonoids and Ar-Oprs were only separated on AICDCSP. These interesting separation results demonstrate that the secondary hydroxyl groups play a pivotal role in the separation of chiral compounds. In addition, the size of the CD cavity and the choice of solute also have an effect on the separation of substances. The mechanism involved in enantioselective discrimination of the selectively substituted CDs was further investigated by the molecular docking simulation.

Differentially expressed platelet activation-related genes in dogs with stage B2 myxomatous mitral valve disease.

BACKGROUND: Peripheral blood carries a reservoir of mRNAs that regulate cardiac structure and function potential. Although it is well recognized that the typical symptoms of Myxomatous Mitral Valve Disease (MMVD) stage B2 are long-standing hemodynamic disorder and cardiac structure remodeling caused by mitral regurgitation, the transcriptomic alterations in blood from such dogs are not understood. RESULTS: In the present study, comparative high-throughput transcriptomic profiling of blood was performed from normal control (NC) and naturally-occurring MMVD stage B2 (MMVD) dogs. Using Weighted Gene Co-expression Network Analyses (WGCNA), Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genomes (KEGG), we identified that the turquoise module was the most highly correlated with echocardiographic features and found 64 differentially expressed genes (DEGs) that were significantly enriched in platelet activation related pathways. Therefore, from the turquoise module, we selected five DEGs (MDM2, ROCK1, RIPK1, SNAP23, and ARHGAP35) that, according to real-time qPCR, exhibited significant enrichment in platelet activation related pathways for validation. The results showed that the blood transcriptional abundance of MDM2, ROCK1, RIPK1, and SNAP23 differed significantly (P < 0.01) between NC and MMVD dogs. On the other hand, Correlation Analysis revealed that MDM2, ROCK1, RIPK1, and SNAP23 genes negatively regulated the heart structure parameters, and followed the same trend as observed in WGCNA. CONCLUSION: We screened four platelet activation related genes, MDM2, ROCK1, RIPK1, and SNAP23, which may be considered as the candidate biomarkers for the diagnosis of MMVD stage B2. These findings provided new insights into MMVD pathogenesis.

Application of three-dimensional printing individualized titanium mesh in alveolar bone defects with different Terheyden classifications: A retrospective case series study.

OBJECTIVE: To present the results of guided bone regeneration (GBR) with three-dimensional printing individualized titanium mesh (3D-PITM) applied to alveolar bone defects with different Terheyden classifications and the factors affecting the osteogenic outcome. MATERIALS AND METHODS: Fifty-nine patients, presenting with 61 defect sites, were enrolled between 2018 and 2021. GBR+3D-PITM was obtained with simultaneous or second stage implant placement. The complication rate, the success rate of the bone grafting procedure and the survival rate of the implant were documented. Bone gain, thickness of pseudo-periosteum and peri-implant marginal bone loss (MBL) were measured through digital methods by imaging data (CBCT and X-ray). RESULTS: Out of 61 sites, 20 were exposed (exposure rate: 32.8%). The width, height, and volume bone gain at P3 (mesh removal) were 5.22 ± 3.19 mm, 5.01 ± 2.83 mm, and 588.91 ± 361.23 mm3 , respectively. From P2 (3D-PITM+GBR) to P3 , changes in bone gain were not statistically different in the different Terheyden classifications, the occurrence of exposure (p < .001 for all dimensions) and the different type of pseudo-periosteum (p = .030 for width and p = .002 for height) were significantly correlated with the reduction of bone gain. Terheyden classification of the defect sites was significantly associated with the occurrence of exposure (p = .014) and types of the pseudo-periosteum (p = .015). CONCLUSION: The 3D-PITM can be used in alveolar bone defects with different Terheyden classification, but cases with severe vertical bone defects have a greater chance of the 3D-PITM exposure and the exposure can affect the outcome of bone augmentation.

Surface-up click access to allylimidazolium bridged cyclodextrin dimer phase for efficient enantioseparation.

In this work, a novel allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase was fabricated via a surface-up thiol-ene click chemistry reaction between 7-SH-ß-cyclodextrin and 1-allylimidazole-ß-cyclodextrin bonded on a silica surface. The structure of the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase was characterized by Fourier transform infrared spectra, 13 C nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. Its chiral chromatographic performances were systematically evaluated by separating 35 racemic analytes including isoxazolines, dansyl-amino acids, and flavanones under reversed-phase high-performance liquid chromatography. Compared with the corresponding bottom and top layer of the ß-cyclodextrin stationary phase, the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase afforded significantly accentuated chiral recognition ability due to its abundant hydrogen bond sites, electrostatic interactions, and synergistic inclusion. Furthermore, the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase showed better enantioseparation ability compared to other reported bridged cyclodextrin stationary phases. In particular, Ar-Phs and dansyl-amino acid could be completely separated by allylimidazolium-bridged bis(ß-mono-6A -deoxy-6-allylimidazolium-ß-cyclodextrin chiral stationary phase) chiral stationary phase with high resolutions of 1.14-7.20 and 3.16-5.82, respectively. Molecular docking reveals that good enantioseparation ability arises from the different interaction modes and the synergistic effect of allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase.

A meta-analysis of mRNA expression profiling studies in sheep with different FecB genotypes.

The FecB mutation in the sheep BMPRIB is strongly correlated with high ovulation traits but its mechanism remains unclear. This study explored differentially expressed genes (DEGs) and their associated molecular mechanisms that may be involved in FecB mutation-induced high ovulation from the perspective of the hypothalamic-pituitary-gonadal (HPG) axis by conducting a systematic review and meta-analysis. The PubMed, EMBASE, CNKI, WanFang, and CBM databases were searched for eligible articles published before August 2022, focusing on mRNA sequencing of different tissues in the HPG axis in sheep with different FecB genotypes. A total of 6555 DEGs were identified from the analysis of six published articles and experimental results from our laboratory. The DEGs were screened by vote-counting rank and robust rank aggregation. Among these, in the follicular phase, FKBP5, CDCA7 and CRABP1 were upregulated in the hypothalamus. INSM2 was upregulated, while LDB3 was downregulated in the pituitary. CLU, SERPINA14, PENK, INHA and STAR were upregulated, while FERMT2 and NPY1R were downregulated in the ovary. On the HPG axis, TAC1 was upregulated and NPNT was downregulated. Many DEGs were found in sheep with different FecB genotypes. The genes FKBP5, CDCA7, CRABP1, INSM2, LDB3, CLU, SERPINA14, PENK, INHA, STAR, FERMT2, NPY1R, TAC1 and NPNT, may be associated with FecB mutation-induced high ovulation in different tissues. These candidate genes will further improve the mechanism of multiple fertility traits induced by the FecB mutation from the perspective of the HPG axis.

Recent advances in anti-inflammatory active components and action mechanisms of natural medicines.

Inflammation is a series of reactions caused by the body's resistance to external biological stimuli. Inflammation affects the occurrence and development of many diseases. Anti-inflammatory drugs have been used widely to treat inflammatory diseases, but long-term use can cause toxic side-effects and affect human functions. As immunomodulators with long-term conditioning effects and no drug residues, natural products are being investigated increasingly for the treatment of inflammatory diseases. In this review, we focus on the inflammatory process and cellular mechanisms in the development of diseases such as inflammatory bowel disease, atherosclerosis, and coronavirus disease-2019. Also, we focus on three signaling pathways (Nuclear factor-kappa B, p38 mitogen-activated protein kinase, Janus kinase/signal transducer and activator of transcription-3) to explain the anti-inflammatory effect of natural products. In addition, we also classified common natural products based on secondary metabolites and explained the association between current bidirectional prediction progress of natural product targets and inflammatory diseases.

Evaluation on the inclusion behavior of ß-cyclodextrins with lycorine and its hydrochloride.

Lycorine (Lyc) and its hydrochloride (Lyc∙HCl) as effective drugs can fight against many diseases including novel coronavirus (COVID-19) based on their antiviral and antitumor mechanism. Beta-cyclodextrin (ß-CD) is considered a promising carrier in improving its efficacy while minimizing cytotoxicity due to the good spatial compatibility with Lyc. However, the detailed mechanism of inclusion interaction still remains to be further evaluated. In this paper, six inclusion complexes based on ß-CDs, Lyc and Lyc∙HCl were processed through ultrasound in the mixed solvent of ethanol and water, and their inclusion behavior was characterized after lyophilization. It was found that the inclusion complexes based on sulfobutyl-beta-cyclodextrin (SBE-ß-CD) and Lyc∙HCl had the best encapsulation effect among prepared inclusion complexes, which may be attributed to the electrostatic interaction between sulfonic group of SBE-ß-CD and quaternary amino group of Lyc∙HCl. Moreover, the complexes based on SBE-ß-CD displayed pH-sensitive drug release property, good solubilization, stability and blood compatibility, indicating their potential as suitable drug carriers for Lyc and Lyc∙HCl.

Biomimic Heterostructured Graphene Oxide Membranes via Supramolecular-Mediated Intercalation Assembly for Efficient Water Transport.

Two-dimensional (2D) lamellar membranes have attracted increasing attention for efficient water purification. However, the low water-permeability, structural failure in aqua and high production cost have significantly restricted their practical large-scale applications. Inspired by the structures of glomerular filtration barrier (GFB) and nacre, a high-performance biomimic membrane via supramolecular-mediated intercalation assembly is reported, where rod-shaped cyclodextrin (CD) functionalized attapulgite (ATP-CD) is intercalated into CD-modified graphene oxide (GO-CD) lamellar channels, followed by locking adjacent ATP-CD and GO-CD through tannic acid (TA) and CD supramolecular networks. The formed GFB-like heterostructure endows the membrane with excellent water transport capability and the bionic "brick and mortar" nacre configuration boosts its anti-swelling stability simultaneously. The heterostructured GO membranes (≈100 nm) fabricated in this way exhibit a good water permeability of 55.6 L m-2  h-1  bar-1 (≈20-fold higher than GO membrane) maintaining excellent dye rejection of >99% during 480 h immersion. Given the low-cost materials (ATP, CD, and TA) and the modification generality, this economic strategy can hopefully achieve large-scale membrane fabrication and afford high applicability, which promotes the practical engineering applications of such 2D material membranes.

Passively Q-switched single crystal fiber pulsed laser at 1.05†µm with T3C2Tx as the saturable absorber.

In this paper, Ti3C2Tx MXene prepared by LiF/HCl etching method was spin-coated on glass substrate and sapphire substrate as the saturable absorber (SA), and the MXene SA is combined with Yb: LuAG single crystal fiber (SCF) for the first time to achieve a 1.05 µm passively Q-switched pulsed laser output with the average power, pulse width, and repetition frequency of 1.989 W, 149.6 ns, and 365.44 kHz, respectively, which is the highest average power ever reported for passively Q-switched SCF pulsed lasers. This work enriches the research on SCF pulsed lasers and provides a feasible approach for achieving high-power all-solid-state pulsed lasers.

Investigation on improvement of enantioseparation in capillary electrophoresis based on maltodextrin by chiral ionic liquids.

Taking advantage of chiral ionic liquids, this study deals with the improvement of the enantioseparation performance of a traditional chiral selector (maltodextrin) in capillary electrophoresis. Herein, two polyhydroxy compound-based chiral ionic liquids, namely tetramethylammonium-D-gluconic acid and tetramethylammonium-shikimic acid were designed and utilized as additives for chiral separation for the first time. The synergistic systems provided much better enantioseparations of twelve model drugs compared to the single maltodextrin system. These model analytes contained analgesics, antidepressants, antiallergic drugs, antifungal drugs, antihypertensive drugs, and antiparkinsonian drugs. After optimizing the separation conditions, the chiral recognition mechanism was probed by means of ultraviolet spectroscopy, nuclear magnetic resonance, and molecular modeling. The results of spectroscopic and computational analyses were in good consistency with enantioseparation outcomes. Finally, the proposed method was successfully used for the determination of the enantiomeric purity of duloxetine hydrochloride.

Development and validation of a reversed-phase high-performance liquid chromatography-ultraviolet method for abemaciclib-related substance detection in bulk drugs.

Abemaciclib is an effective selective cyclin-dependent kinases 4 and 6 inhibitors for cancer therapy. The abemaciclib-related substances influence its efficacy and safety, and are important in process preparation studies and quality control. Thus, a reversed-phase high-performance liquid chromatography method was developed and validated for the detection of related substances in its bulk drug. The separation of abemaciclib and related substances was performed on a Phenomenon Gemini C18 column (4.6 × 250 mm, 5 µm) with a flow rate of 1.0 ml/min. The ultraviolet detection wavelength was 280 nm. Mobile phase A was composed of a mixed solution of aqueous solution and acetonitrile (9:1, v/v). The aqueous solution (pH 2.5) contained 0.025-mM potassium dihydrogen phosphate solution and 0.4% triethylamine. Mobile phase B was composed of acetonitrile. This novel method exhibits good system suitability, specificity, precision, stability, linearity (0.1-20 µg/ml), repeatability, and durability. Among abemaciclib and related substances, the lowest limit of detection and quantitation were 0.02 and 0.06 µg/ml, respectively, for abemaciclib. The recovery rates for related substances were above 95%. In addition, a novel degradation product was found during the process. In summary, a reliable reversed-phase high-performance liquid chromatography method was developed for abemaciclib-related substance detection in bulk drugs.

Correlation between intervertebral disc degeneration and bone mineral density difference: a retrospective study of postmenopausal women using an eight-level MRI-based disc degeneration grading system.

PURPOSE: To explore the correlation between intervertebral disc degeneration (IDD) and bone mineral density (BMD) difference between adjacent vertebrae. METHODS: A retrospective analysis of 114 postmenopausal women who were treated in our hospital from January 2021 to December 2021. The degree of lumbar(L)1-5 IDD was scored according to an 8-grade scoring system. The lumbar vertebrae BMD was detected, and the BMD difference was calculated. The subjects were grouped according to age and whether the disc was severe IDD. Data were collected for statistical analysis. RESULTS: The prevalence of osteoporosis in the 51-60-year-old group was lower than that in the other groups, while the prevalence of modic changes in the 71-80-year-old group was higher than that in the 51-70-year-old group (P < 0.05). At the L1/2 level, the prevalence of severe IDD in the 81-90y group was higher than that in the 51-70y group (P < 0.05). At the L2/3 level, the prevalence of severe IDD in the 71-90y group was higher than that in the 51-60y group, and the prevalence of severe IDD in the 71-80y group was higher than that in the 61-70y group (P < 0.05). The L2/3 disc score was positively correlated with the L3-L2 BMD difference (P < 0.05). At the level of L1-2, the BMD difference in the non-severe IDD group was smaller than that in the severe IDD group (P < 0.05). CONCLUSION: For postmenopausal women, an increase in BMD difference is correlated with IDD. Osteoporosis is more common in people over 60 years old, and the possibility of modic change in 71-80y is higher than in other age groups. The incidence of severe IDD also increases with aging, especially for the L1/2 and L2/3 discs.