Chirality Supramolecular Systems: Helical Assemblies, Structure Designs, and Functions.

Chirality, as one of the most striking characteristics, exists at various scales in nature. Originating from the interactions of host and guest molecules, supramolecular chirality possesses huge potential in the design of functional materials. Here, an overview of the recent progress in structure designs and functions of chiral supramolecular materials is present. First, three design routes of the chiral supramolecular structure are summarized. Compared with the template-induced and chemical synthesis strategies that depend on accurate molecular identification, the twisted-assembly technique creates chiral materials through the ordered stacking of the nanowire or films. Next, chirality inversion and amplification are reviewed to explain the chirality transfer from the molecular level to the macroscopic scale, where the available external stimuli on the chirality inversion are also given. Lastly, owing to the optical activity and the characteristics of the layer-by-layer stacking structure, the supramolecular chirality materials display various excellent performances, including smart response, shape-memorization, superior mechanical performance, and applications in biomedical fields. To sum up, this work provides a systematic review of the helical assemblies, structure design, and applications of supramolecular chirality systems.

Uncovering the Recent Progress of CNC-Derived Chirality Nanomaterials: Structure and Functions.

Cellulose nanocrystal (CNC), as a renewable resource, with excellent mechanical performance, low thermal expansion coefficient, and unique optical performance, is becoming a novel candidate for the development of smart material. Herein, the recent progress of CNC-based chirality nanomaterials is uncovered, mainly covering structure regulations and function design. Undergoing a simple evaporation process, the cellulose nanorods can spontaneously assemble into chiral nematic films, accompanied by a vivid structural color. Various film structure-controlling strategies, including assembly means, physical modulation, additive engineering, surface modification, geometric structure regulation, and external field optimization, are summarized in this work. The intrinsic correlation between structure and performance is emphasized. Next, the applications of CNC-based nanomaterials is systematically reviewed. Layer-by-layer stacking structure and unique optical activity endow the nanomaterials with wide applications in the mineralization, bone regeneration, and synthesis of mesoporous materials. Besides, the vivid structural color broadens the functions in anti-counterfeiting engineering, synthesis of the shape-memory and self-healing materials. Finally, the challenges for the CNC-based nanomaterials are proposed.

Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.

BACKGROUND: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. METHODS: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. RESULTS: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. CONCLUSIONS: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.

Synthesis of Oil-Soluble Polymer-Grafted Carbon Dots with Outstanding Colloidal Stability and Tribological Properties in Polyalphaolefin.

Herein, a series of polylauryl methacrylate-grafted CDs (CDs-PLMA-m, m denotes the reaction time in hours) with core-shell structure were synthesized via surface-initiated atom-transfer radical polymerization (SI-ATRP). Due to the good solubility of PLMA in hydrocarbons, all of the CDs-PLMA-m can be facilely dispersed in polyalphaolefin (PAO) to form pellucid colloidal dispersions. The reciprocating ball-on-plate sliding friction tests proved that the addition of 3.0 wt % CDs-PLMA-1 markedly lessened the wear and friction of PAO by 53.0 and 40.0%, respectively. The tribological performances of the CDs-PLMA-1 (3.0 wt %)/PAO dispersion did not attenuate sharply when the friction duration extended from 20 to 200 min or the applied load increased from 20 to 100 N, revealing the long lifetime and desirable load-carrying effect of CDs-PLMA-1. Based on the friction tests, the antifriction behavior of CDs-PLMA-1 was related to the synergies between the molecular lubrication of PLMA-1 brushes and the nanolubrication of CDs. Furthermore, the wear analyses disclosed the deposition of tribofilm composed of a lot of CDs-PLMA-1 and a spot of iron oxides, which provided oxidation resistance and an antiwear function. This study established a reliable route to the synthesis of oil-soluble polymer-grafted CDs, enabling high-efficiency lubrication of CDs in PAO.

How health risk factors affect inpatient costs among adults with stroke in China: the mediating role of length of stay.

BACKGROUND: As stroke has become the leading cause of death and disability in China, it has induced a heavy disease burden on society, families, and patients. Despite much attention within the literature, the effect of multiple risk factors on length of stay (LOS) and inpatient costs in China is still not fully understood. AIM: To analyse the association between the number of risk factors combined and inpatient costs among adults with stroke and explore the mediating effect of LOS on inpatient costs. METHODS: A retrospective cross-sectional study was conducted among stroke patients in a tertiary hospital in Nantong City from January 2018 to December 2019. Lifestyle factors (smoking status, exercise), personal disease history (overweight, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation), family history of stroke, and demographic characteristics were interviewed by trained nurses. Inpatient costs and LOS were extracted from electronic medical records. Hierarchical multiple linear regression models and mediation analysis were used to examine the direct and indirect effects of the number of risk factors combined for stroke on inpatient costs. RESULTS: A total of 620 individuals were included, comprising 391 ischaemic stroke patients and 229 haemorrhagic stroke patients, and the mean age was 63.2 years, with 60.32% being male. The overall mean cost for stroke inpatients was 30730.78 CNY ($ 4444.91), and the average length of stay (LOS) was 12.50 days. Mediation analysis indicated that the greater number of risk factors was not only directly related to higher inpatient costs (direct effect = 0.16, 95%CI:[0.11,0.22]), but also indirectly associated with inpatient cost through longer LOS (indirect effect = 0.08, 95% CI: [0.04,0.11]). Furthermore, patients with high risk of stroke had longer LOS than those in low-risk patients, which in turn led to heavier hospitalization expenses. CONCLUSIONS: Both the greater number of risk factors and high-risk rating among stroke patients increased the length of stay and inpatient costs. Preventing and controlling risk behaviors of stroke should be strengthened.

Bifunctional Chiral Agent Enables One-pot Spontaneous Deracemization of Racemic Compounds.

A novel one-pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α-diphenyl-2-pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)-enantiomer and (2S,3S)-enantiomer in solution, achieving a one-pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)-carprofen, (R,S)-indoprofen, and (R,S)-indobufen. The one-pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization-induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.

Photo-Amplified Plasma Membrane Rupture by Membrane-Anchoring NIR-II Small Molecule Design for Improved Cancer Photoimmunotherapy.

Immunotherapy is a promising cancer treatment method for eradicating tumor cells by enhancing the immune response. However, there are several major obstacles to conventional phototherapy-mediated immune responses, including inadequate immunogenicity and immunosuppressive environment. Here, we present a novel photoimmunotherapy modality-the development of membrane-anchoring small molecule inducing plasma membrane rupture (PMR) by NIR-II photo-stimulation, thus evoking cell necrotic death and enhancing antitumor immunotherapy. Our top-performing membrane-anchoring small molecule (CBT-3) exhibits temperature-tunable PMR efficiency, allowing rapid necrotic death in cancer cells at 50 µM dose by using exogenous NIR-II light-mediated mild photothermal effect (1064 nm, 0.6 W cm-2). Further evidence indicated that this gentle therapeutic approach activated inflammatory signaling pathways in cells, enhanced immunogenic cell death, and reshaped the immunosuppressive tumor microenvironment, ultimately promoting systemic antitumor immune responses in vivo. This study represents the first instance of utilizing NIR-II photo-amplified PMR effect based on membrane-anchoring small molecule, providing a novel avenue for advancing cancer photoimmunotherapy.

Authentication of Single Herbal Powders Enabled by Microscopy-Guided In Situ Auto-sampling Combined with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.

In the long history of investigation of herbal products, microscopic examination has greatly contributed to the authentication of herbs in a powder form. However, it cannot provide the chemical profiles of herbal powders and thus is limited to morphological identification. In this work, we present a label-free and automatic approach for the characterization and identification of single herbal powders and their adulterants, enabled through the combination of microscopy-guided auto-sampling and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). To meet the demand for automatic and highly efficient in situ extraction, the glass slide was coated with gelatin to immobilize dried herbal powders that cannot stick to the glass slide like fresh and hydrated cells. The gelatin coating also facilitated the pump-out of chemical components and prevented diffusion across the interface enabled by the formation of a tight contact at the probe tip and surface. Optical microscopy was applied to acquire the microstructure and position of the herbal powders immobilized on the gelatin-coated slide. The candidate single herbal powders were picked out by a software for subsequent auto-sampling and MALDI MS identification. The combination of microstructure features and chemical profiles significantly improved the authentication capability of microscopic examination.

Development of an Efficient On-Tissue Epoxidation Reaction Mediated by Urea Hydrogen Peroxide for MALDI MS/MS Imaging of Lipid C═C Location Isomers.

Unsaturated lipids containing different numbers and locations of C═C bonds are significantly associated with a variety of cellular and metabolic functions. Although matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has been used to visualize the spatial distribution patterns of various lipids in biological tissues, in situ identification, discrimination, and visualization of lipid C═C location isomers remain challenging. Herein, an efficient and fast on-tissue chemical derivatization (OTCD) approach was developed to pinpoint the locations of C═C bonds in complex lipids in situ via methyltrioxorhenium (MTO)-catalyzed epoxidation of C═C with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. The efficiency of OTCD could reach 100% via one-step spray deposition of the solution mixture of MTO/UHP/HFIP at room temperature. The developed OTCD method provided rich structural information on lipid C═C location isomers, and their accurate spatial distribution patterns were resolved in mouse brain tissues. Tissue-specific distributions and changes of lipid C═C location isomers in the liver sections of obese ob/ob and diabetic db/db mice were further investigated, and their correlation in two animal models was revealed. The simplicity and high efficiency of the OTCD method developed for MALDI tandem MSI of lipid C═C location isomers possess great potential for functional spatial lipidomics.

Evaluation of Intestinal Drug Absorption and Interaction Using Quadruple Single-Pass Intestinal Perfusion Coupled with Mass Spectrometry Imaging.

Visualization and characterization of the intestinal membrane transporter-mediated drug absorption and interaction are challenging due to the complex physical and chemical environment. In this work, an integrated strategy was developed for in situ visualization and assessment of the drug absorption and interaction in rat intestines using quadruple single-pass intestinal perfusion (Q-SPIP) technique coupled with matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). Compared with the traditional SPIP only available for perfusion of one single intestinal segment, the Q-SPIP model can simultaneously perfuse four individual segments of each rat intestine (duodenum, jejunum, ileum, and colon), enabling to obtain rich data from one rat. Subsequently, the drug distribution and absorption in rat intestinal tissue were accurately visualized by using an optimized MALDI MSI approach. The utility and versatility of this strategy were demonstrated via the examination of P-glycoprotein (P-gp)-mediated intestinal absorption of berberine (BBR) and its combination with natural products possessing inhibitory potency against P-gp. The change in the spatial distribution of BBR was resolved, and MALDI results showed that the signal intensity of BBR in defined regions was enhanced following coperfusion with P-gp inhibitors. However, enhanced absorption of BBR after coperfusion with the P-gp inhibitor was not observed in the ulcerative colitis rat model, which may be due to the damage to the intestinal barrier. This study exemplifies the availability and utility of Q-SPIP coupled with MALDI MSI in the examination of transporter-mediated intestinal drug absorption and interaction for fundamental inquiries into the preclinical prediction of oral absorption and drug interaction potential.

Overexpression of ClWRKY48 from Cunninghamia lanceolata improves Arabidopsis phosphate uptake.

MAIN CONCLUSION: Our findings suggested that ClWRKY48 promoted the expression level of Arabidopsis phosphate transporter genes, enhanced phosphate uptake, and delayed the transition from the vegetative stage to the reproductive phase in Arabidopsis. Phosphorus (P) is an essential mineral for plants that influences their growth and development. ClWRKY48, one of the most highly expressed genes in the leaf, was identified by RT-PCR from Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] (C. lanceolata). Furthermore, when treating C. lanceolata with increasing phosphate (Pi) concentration, the expression level of ClWRKY48 rose in leaves, the trends followed the increasing phosphate concentration treatment. ClWRKY48 is a transcription factor in C. lanceolata, according to the results of a yeast one hybridization experiment. Based on subcellular localization studies, ClWRKY48 is a nuclear-localized protein. Under Pi deficiency conditions, the phosphorus concentration of ClWRKY48 overexpressing Arabidopsis increased by 43.2-51.1% compared to the wild-type. Moreover, under Pi limiting conditions, the phosphate transporter genes AtPHT1;1 (Arabidopsis Phosphate transporter 1;1), AtPHT1;4, and AtPHO1 (Arabidopsis PHOSPHATE 1) were expressed 2.1-2.5, 2.2-2.7, and 6.7-7.3-fold greater than the wild-type in ClWRKY48 transgenic Arabidopsis, respectively. Under Pi-sufficient conditions, the phosphorus concentration and phosphate transporter genes of ClWRKY48 overexpression in Arabidopsis are not significantly different from the wild type. These findings indicated that ClWRKY48 increased phosphate absorption in transgenic Arabidopsis. Furthermore, compared to the wild type, the ClWRKY48 transgenic Arabidopsis not only had a delayed flowering time characteristic but also had lower expression of flowering-related genes AtFT (FLOWERING LOCUS T), AtFUL (FRUITFUL), and AtTSF (TWIN SISTER OF FT). Our findings show that ClWRKY48 enhances phosphate absorption and slows the transition from the vegetative to the reproductive stage in ClWRKY48 transgenic Arabidopsis.

Ginsenoside Rh1, a novel casein kinase II subunit alpha (CK2α) inhibitor, retards metastasis via disrupting HHEX/CCL20 signaling cascade involved in tumor cell extravasation across endothelial barrier.

Tumor cell extravasation across endothelial barrier has been recognized as a pivotal event in orchestrating metastasis formation. This event is initiated by the interactions of extravasating tumor cells with endothelial cells (ECs). Therefore, targeting the crosstalk between tumor cells and ECs might be a promising therapeutic strategy to prevent metastasis. In this study, we demonstrated that Rh1, one of the main ingredients of ginseng, hindered the invasion of breast cancer (BC) cells as well as diminished the permeability of ECs both in vitro and in vivo, which was responsible for the attenuated tumor cell extravasation across endothelium. Noteworthily, we showed that ECs were capable of inducing the epithelial-mesenchymal transition (EMT) and invadopodia of BC cells that are essential for tumor cell migration and invasion through limiting the nuclear translocation of hematopoietically expressed homeobox (HHEX). The decreased nuclear HHEX paved the way for initiating the CCL20/CCR6 signaling axis, which in turn contributed to damaged endothelial junctions, uncovering a new crosstalk mode between tumor cells and ECs. Intriguingly, Rh1 inhibited the kinase activity of casein kinase II subunit alpha (CK2α) and further promoted the nuclear translocation of HHEX in the BC cells, which resulted in the disrupted crosstalk between chemokine (C-C motif) ligand 20 (CCL20) in the BC cells and chemokine (C-C motif) receptor 6 (CCR6) in the ECs. The prohibited CCL20-CCR6 axis by Rh1 enhanced vascular integrity and diminished tumor cell motility. Taken together, our data suggest that Rh1 serves as an effective natural CK2α inhibitor that can be further optimized to be a therapeutic agent for reducing tumor cell extravasation.

An Interview Study of College Students' Health Emergency Literacy in the Context of COVID-19 Normalized Prevention and Control.

Objective: To explore the changes in college students' awareness of health protection under the normalization of COVID-19, and to seek its connection with the epidemic management in colleges and universities, so as to provide reference information for continuous health education activities and the cultivation of college students' health emergency literacy in colleges and universities. Methods: Qualitative interviews were used to understand the extent of health emergency literacy among college students enrolled in the context of a normalized epidemic and the factors associated with it that cause changes around a question outline. Results: The interviewees generally had a lax mentality in the late stage of the interview, the importance they attached to epidemic prevention and control decreased significantly, and the way to know about epidemic protection measures and other knowledge was mainly through the mass news media. All respondents affirm the importance of social software for outbreak prevention and control. All 17 interviewees were able to mention basic outbreak protection methods, but 15 of them showed inconsistent behavior in words and actions later. Conclusion: The vast majority of respondents' health emergency literacy appears to weaken in the late stages of epidemic normalization, and the effect of traditional approaches used by universities to improve college students' health emergency literacy is weak.

Visible Near-Infrared Photodetection Based on Ta2NiSe5/WSe2 van der Waals Heterostructures.

The increasing interest in two-dimensional materials with unique crystal structures and novel band characteristics has provided numerous new strategies and paradigms in the field of photodetection. However, as the demand for wide-spectrum detection increases, the size of integrated systems and the limitations of mission modules pose significant challenges to existing devices. In this paper, we present a van der Waals heterostructure photodetector based on Ta2NiSe5/WSe2, leveraging the inherent characteristics of heterostructures. Our results demonstrate that this detector exhibits excellent broad-spectrum detection ability from the visible to the infrared bands at room temperature, achieving an extremely high on/off ratio, without the need for an external bias voltage. Furthermore, compared to a pure material detector, it exhibits a fast response and low dark currents (~3.6 pA), with rise and fall times of 278 µs and 283 µs for the response rate, respectively. Our findings provide a promising method for wide-spectrum detection and enrich the diversity of room-temperature photoelectric detection.

Polysaccharides from sea buckthorn (Hippophae rhamnoides L.) berries ameliorate cognitive dysfunction in AD mice induced by a combination of d-gal and AlCl3 by suppressing oxidative stress and inflammation reaction.

BACKGROUND: The therapeutic properties of Hippophae rhamnoides L. were known in Ancient Greece and in Tibetan and Mongolian medicine, which commonly used it for the treatment of heart ailments, rheumatism, and brain disorders. Modern studies have indicated that Hippophae rhamnoides L. polysaccharide (HRP) can improve cognitive impairment in mice with Alzheimer's disease (AD) but the specific mechanisms of the protective effect of HRP have not been elucidated fully. RESULTS: Our results showed that Hippophae rhamnoides L. polysaccharide I (HRPI) improved pathological behaviors related to memory and cognition, and reduced 1 Beta-amyloid (Aß) peptide deposition and neuronal cell necrosis. Pretreatment with Hippophae rhamnoides L. polysaccharide I (HRPI) also decreased the level of Toll-like receptor 4 (TLR4) and Myeloid differentiation factor 88 (MyD88), and reduced the release of inflammatory factors Tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in the brains of mice with AD. Treatment with HRPI also suppressed the expression level of Recombinant Kelch Like ECH Associated Protein 1 (KEAP1), and increased the levels of Nuclear factor erythroid 2-Related Factor 2 (Nrf2), antioxidant enzymes Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in the brains of AD mice. CONCLUSIONS: On the whole, these findings revealed that HRPI could improve the learning and memory ability and attenuate pathologic impairment in AD mice, and the underlying mechanisms may involve mediating oxidative stress and inflammation, possibly through the regulation of the Keap1/Nrf2 and TLR4/MyD88 signaling pathways. © 2023 Society of Chemical Industry.

[Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses].

Objective: To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. Methods: A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Results: Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). Conclusions: As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

MALDI Imaging Assisted Discovery of a Di-O-glycosyltransferase from Platycodon grandiflorum Root.

A matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) assisted genome mining strategy was developed for the discovery of glycosyltransferase (GT) from the root of Platycodon grandiflorum. A di-O-glycosyltransferase PgGT1 was discovered and characterized that is capable of catalyzing platycoside E (PE) synthesis through the attachment of two ß-1,6-linked glucosyl residues sequentially to the glucosyl residue at the C3 position of platycodin D (PD). Although UDP-glucose is the preferred sugar donor for PgGT1, it could also utilize UDP-xylose and UDP-N-acetylglucosamine as weak donors. Residues S273, E274, and H350 played important roles in stabilizing the glucose donor and positioning the glucose in the optimal orientation for the glycosylation reaction. This study clarified two key steps involved in the biosynthetic pathway of PE and could greatly contribute to improving its industrial biotransformation.

Engineered exosomes for co-delivery of PGM5-AS1 and oxaliplatin to reverse drug resistance in colon cancer.

Oxaliplatin resistance inevitably occurs in almost all cases of metastatic colorectal cancer (CRC), and it is important to study the roles of lncRNAs and their specific regulatory mechanisms in oxaliplatin resistance. Exosomes are increasingly designed for drug or functional nucleic acid delivery due to their properties, thereby improving the effectiveness of cancer therapy. The results of this study show that the low expression of PGM5 antisense RNA 1 (PGM5-AS1) in colon cancer is induced by transcription inhibitor, GFI1B. PGM5-AS1 prevents proliferation, migration, and acquired oxaliplatin tolerance of colon cancer cells. Exosomes encapsulating oxaliplatin and PGM5-AS1 can reverse drug resistance. For identifying differentially expressed target genes regarding PGM5-AS1, RNA transcriptome sequencing was performed. The mechanism by which PGM5-AS1 regulates its target genes was explored by performing experiments such as fluorescent in situ hybridization assay, dual-luciferase reporter gene assay, and RNA immunoprecipitation. The results show that by recruiting SRSF3, PGM5-AS1 activates alternate splicing to downregulate PAEP expression. For hsa-miR-423-5p, PGM5-AS1 can also act as a sponge to upregulate the NME1 expression.

SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance.

BACKGROUND: Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance. METHODS: We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER+)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER+ BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression. RESULTS: RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER+ BC patients. CONCLUSIONS: This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.

Kinetic Retraction at the Onset of Concomitant Crystallization and Implication on Polymorphic Formation.

The four-quadrant regimes of attainable polymorph crystallization (FQR-APC) plot was recently developed through numerical simulations of crystallization kinetics of a dipolymorphic system. Retraction in the polymorphic composition of the most stable form in crystallized samples was unveiled a characteristic indication of concomitant polymorphism. Comparisons were made with a recently developed concept, the Ostwald ratio (OR), in light of characterization of polymorphic formation. It was shown that both schemes display a good agreement in describing polymorphic outcomes, despite their distinct theoretical origins.