Association between neutrophil-to-lymphocyte ratio and motor subtypes in idiopathic Parkinson's disease: a prospective observational study.

BACKGROUND: Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. METHODS: This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. RESULTS: A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1ßand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1ß in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1ß plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1ß was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1ß showed better performance in identifying the AR motor subtype. CONCLUSION: NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD.

An adhesive hydrogel functionalized silica sphere for polar analytes separation and analysis.

In response to the challenges associated with the chromatographic separation of polar compounds, this study aims to devise a solution by introducing a novel stationary phase. Hydrogels, characterized by a three-dimensional network structure, have aroused wide attention owing to its functional designability, multiple interaction sites and good adhesion, etc. In this work, an adhesive hydrogel functionalized silica stationary phase (Sil@PVA/TA) was synthesized using physical coating technique. Due to the co-existence of hydroxyl and benzene ring in the hydrogel structure, the obtained composites materials exhibited excellent separation performance for various of compounds and excellent column efficiency up to 71385.6 plates/m for thymidine. Furthermore, the hydrogel functionalized silica demonstrated superior selectivity to bare silica, diol-column and NH2-column for the separation of various of polar molecules, including, nucleosides/bases, alkaloids, organic acids, antibiotics and amino acids. Notably, for alkaloids, which frequently encounter peak tailing issues, Sil@PVA/TA demonstrated superior peak shape compared with C18 column. In short, this study successfully synthesized a hydrogel functionalized silica stationary phase, offering a novel method for the separation and analysis of polar compounds.

Polyoxometalates tailoring of frustrated Lewis pairs on Ce-doped Bi2O3 for boosting photocatalytic CO2 reduction.

Constructing frustrated Lewis pairs (FLPs) on catalysts will provide catalytic sites to activate CO2 and boost photocatalytic CO2 reduction. Herein, a Ce-doped bismuth oxide (CeBiOX) with FLPs was designed by loading [(α-SbW9O33)2Cu3(H2O)3]12- (Cu3) via strong electrostatic interactions to create oxygen vacancies (OVs). Detailed experiments and measurements showed that Cu3 could regulate the FLPs and optimize the band structure of CeBiOX to boost photocatalytic CO2 reduction. In particular, the Cu3/CeBiOX composite exhibited the highest yields of CO (42.85 µmoL g-1) and CH4 (13.23 µmoL g-1), being 6.6 and 3.3 times, and 4.9 and 6.3 times higher than those of pristine Bi2O3 and CeBiOX, respectively. This work provides a significant and mild approach to obtaining advanced catalysts with tuneable FLPs for more fields.

CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.

With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4+ T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4+ T-cells in NDs. In this review, we summarize the classification and function of CD4+ T-cell subpopulations, the characteristics of CD4+ T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4+ T-cell senescence.

Adjustable chromatographic performance of silica-based mixed-mode stationary phase through the control of co-grafting amounts of imidazole and C18 chain.

In this paper, three imidazole- and C18- bifunctional silica stationary phases (Sil-Im-C18) were prepared by adjusting introduction interval of octadecyltrichlorosilane (ODS) and 3-imidazol-1-ylpropyl(trimethoxy)silane (TMPImS), which can be used for reversed-phase liquid chromatography (RPLC) and ion exchange chromatography (IEC) with adjustable performance. The successful preparation of Sil-Im-C18 were confirmed by the characterizations of elemental analysis, infrared spectroscopy (FTIR) and contact angle (CA). Chromatographic performance of Sil-Im-C18 were evaluated by the separation of Tanaka test mixture, alkylbenzenes, linear PAHs and a set of analytes with different properties (uracil, phenol, 1,2-dinitrobenzene and naphthalene), and compared with commonly used C18 column. It was found that the chromatographic performance of Sil-Im-C18 changed significantly with the difference in bonding amount of imidazole and C18. Sil-Im-C18 demonstrated the excellent separation performance towards polycyclic aromatic hydrocarbons (PAHs), phenylesters, phenylamines, phenols and inorganic anions, and notably, nucleobases and nucleosides can be separated using pure water as mobile phases. The van Deemter plot showed that the column efficiency of Sil-Im-C18-3 was 64,933 plate·m-1 for naphthalene, indicated that Sil-Im-C18 was reasonably chromatographic columns. The RSD values of retention time were 0.22 %-0.61 % for 10 needles alkylbenzenes injected continuously at 50 °C to investigate thermal stability and repeatability, all the fluctuations of k of naphthalene were less than 2.3 % for Sil-Im-C18-1 during flushing 24 h with the mobile phase at different pH values (pH = 3 and 8), the retention time of alkylbenzenes were almost same for Sil-Im-C18-1 at different time, the RSD values of retention time of alkylbenzenes were 0.45 %-2.28 % for two batches Sil-Im-C18-1, revealing the excellent repeatability, thermal stability, durability and reproducibility of Sil-Im-C18, and implying a commercial prospect.

Dispersive hierarchically porous composites based on defective MOFs as mixed-mode stationary phases for chromatographic separation.

Defective metal-organic frameworks-based composites with excellent separation properties were obtained. The mesoporous metal-organic frameworks were selected and deliberately designed to be deficient, and they were then combined with polyacrylamide to be modified on the surface of silica microspheres. The prepared composites were employed as mixed-mode stationary phase in chromatographic separation, and they were compared to both conventional microporous metal-organic framework-based columns and commercial columns. It showed improved selectivity and retention toward both hydrophilic and hydrophobic analytes, allowing for the effective separation of nine nucleosides and nucleobases, eight alkaloids, six antibiotics, and five alkylbenzenes. Additionally, the column was used to effectively separate the active ingredients in the daring substance of honeysuckle, revealing a wide range of possible applications. For the same batch of analytes, three batches of distinct materials demonstrated consistent separation effects. It also demonstrated excellent chromatographic repeatability and stability, with relative standard deviations of the retention time and/or column efficiency being found to be less than 0.8% and 0.9%, respectively. The dispersive hierarchically porous composites were demonstrated to be effective in chromatographic separation, and the results expanded the potential uses of defective MOFs with dispersed multi-level pores.

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.

Metal ions exert pivotal functions within the human body, encompassing essential roles in upholding cell structure, gene expression regulation, and catalytic enzyme activity. Additionally, they significantly influence various pathways implicated in divergent mechanisms of cell death. Among the prevailing malignant tumors of the digestive tract worldwide, gastric cancer stands prominent, exhibiting persistent high mortality rates. A compelling body of evidence reveals conspicuous ion irregularities in tumor tissues, encompassing gastric cancer. Notably, metal ions have been observed to elicit distinct contributions to the progression, drug resistance, and biological attributes of gastric cancer. This review consolidates pertinent literature on the involvement of metal ions in the etiology and advancement of gastric cancer. Particular attention is directed towards metal ions, namely, Na, K, Mg, Ca, Fe, Cu, Zn, and Mn, elucidating their roles in the initiation and progression of gastric cancer, cellular demise processes, drug resistance phenomena, and therapeutic approaches.

Ursodeoxycholic acid and 18ß-glycyrrhetinic acid alleviate ethinylestradiol-induced cholestasis via downregulating RORγt and CXCR3 signaling pathway in iNKT cells.

Estrogen-induced intrahepatic cholestasis (IHC) is a mild but potentially serious risk and urges for new therapeutic targets and effective treatment. Our previous study demonstrated that RORγt and CXCR3 signaling pathway of invariant natural killer T (iNKT) 17 cells play pathogenic roles in 17α-ethinylestradiol (EE)-induced IHC. Ursodeoxycholic acid (UDCA) and 18ß-glycyrrhetinic acid (GA) present a protective effect on IHC partially due to their immunomodulatory properties. Hence in present study, we aim to investigate the effectiveness of UDCA and 18ß-GA in vitro and verify the accessibility of the above targets. Biochemical index measurement indicated that UDCA and 18ß-GA presented efficacy to alleviate EE-induced cholestatic cytotoxicity. Both UDCA and 18ß-GA exhibited suppression on the CXCL9/10-CXCR3 axis, and significantly restrained the expression of RORγt in vitro. In conclusion, our observations provide new therapeutic targets of UDCA and 18ß-GA, and 18ß-GA as an alternative treatment for EE-induced cholestasis.

Preparation and extraction property study of corn cob-like magnetic mosaic carbon materials derived from MOF-on-MOF composites.

BACKGROUND: Large accumulations of pesticide residues in the environment eventually enter the human body with food. Based on magnetic solid-phase extraction (MSPE) technology, it is possible to achieve efficient extraction of trace pesticide residues in foodstuffs, and the construction of MSPE adsorbents with excellent magnetic properties and many active sites is still one of the main research topics. Based on this, we developed a new strategy for the preparation of "MOF-on-MOF" composites, which were carbonized and used as adsorbents for the extraction of pesticide residues in cereals. RESULTS: A novel corn cob core-shell composite Fe2O3@C@ZIF-8 was created by embedding ZIF-8 onto the surface of Fe2O3@C derived from MIL-88A(Fe), and used for the extraction of benzoylurea insecticides(BUs) from cereals. The adsorption behaviour between Fe2O3@C@ZIF-8 and BUs was investigated by static and kinetic experiments and the adsorption mechanism was elaborated. For the trace analysis of BUs, a magnetic solid-phase extraction combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) approach was also developed. Under the optimized experimental conditions, the limits of detection and quantification were 0.015-0.03 µg L-1 and 0.05-0.1 µg L-1, and the relative standard deviations for the intra-day and inter-day ranges were 1.82%-2.13 % and 3.85%-4.59 %, respectively. The spiked recoveries of the four cereals ranged from 82.72% to 104.45 %. After 10 cycles of use of Fe2O3@C@ZIF-8, the recoveries of BUs ranged from 77.90% to 96.74 %. SIGNIFICANCE: The analytical method based on Fe2O3@C@ZIF-8 as adsorbent has a low limit of detection, a wide linear range and is highly applicable to the analysis of real samples. In addition, the strategy developed in this study for the preparation of thermoplastic polymer-assisted "MOF-on-MOF" composites has promising applications.

Plasma TNF-α and phosphorylated α-syn are associated with fatigue in patients with Parkinson's disease.

BACKGROUD: Fatigue is one of the most common non-motor symptoms among patients with Parkinson's disease (PD).However, the pathogenesis keeps largely unknown. Moreover, it is lack of objective biomarker. OBJECTIVE: To investigate the relationship between plasma inflammatory cytokines and α-syn levels and fatigue in patients with PD. METHODS: A total of 63 PD patients were enrolled, including 35 patients with fatigue and 28 patients without fatigue. We compared the difference between plasma cytokines and alpha-synuclein (α-syn) in the two groups. Meanwhile, we analyzed the relationship between plasma cytokines and p-α-syn levels and fatigue. RESULTS: PD patients with fatigue had older age, longer disease duration, more severe motor scores. There were significant differences in the plasma levels of IL-1ß, IL-18, TNF-α, and phosphorylated α-syn (p-α-syn) between the two groups. The plasm inflammatory cytokine levels (IL-1ß, IL-18 and TNF-α) were positively associated with FSS scores. Moreover, the plasma p-α-syn level was significantly positively correlated with FSS scores. Furthermore, the higher PDQ-39 scores and higher plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD. The ROC curve analysis showed the AUC of TNF-α for fatigue in PD was 0.663 with a sensitivity of 65.71% and specificity of 67.86%, while the AUC of p-α-syn was 0.786 with a sensitivity of 74.29% and specificity of 64.29%. The combination of TNF-α and p-α-syn improves the AUC to 0.803 with a sensitivity of 88.57% and specificity of 64.29%. CONCLUSION: The high plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD.

A composite hydrogel modified silica stationary phase for mixed­mode liquid chromatography.

A novel composite hydrogel functionalized silica core-shell stationary phase was prepared by the surface modification of silica sphere. The successful synthesis of the new stationary phase (T-Sil@PAM/SA/UiO-66-NH2) was proven by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD), etc. Due to the coexistence of amide, hydroxyl, long carbon chain and UiO-66-NH2 in composite hydrogel shell, the obtained stationary phase can be used in hydrophilic/reversed-phase liquid chromatography with multiple retention mechanisms, such as hydrophilic, hydrophobic and π - π interactions. The chromatographic retention behavior of T-Sil@PAM/SA/UiO-66-NH2 demonstrated that the new stationary phase showed excellent separation performance for both polar analytes (such as alkaloids, saccharides, etc.) and nonpolar analytes (such as substituted benzene and polycyclic aromatic hydrocarbon (PAHs), etc.). Furthermore, compared with NH2 column and commercial C18 column, the T-Sil@PAM/SA/UiO-66-NH2 exhibited a certain superiority. Moreover, the relative standard deviation (RSD) of PAHs' retention time with eight replicates consecutive elution was found to range from 0.03% to 0.17%. Therefore, the successful use of T-Sil@PAM/SA/UiO-66-NH2 in mixed­mode liquid chromatography expanded the potential applications of hydrogels in the field of separation.

A stable core-shell metal-organic framework@covalent organic framework composite as solid-phase extraction adsorbent for selective enrichment and determination of flavonoids.

Hydrophobization and stability is crucial for the practical application of most metal-organic frameworks (MOFs) in extraction technique. In this study, a stable core-shell MOF@COF composite (NH2-MIL-101(Fe)@TAPB-FPBA-COF) was successfully prepared by Schiff base reaction and applied to solid-phase extraction (SPE) of hydrophobic flavonoids. Notably, the TAPB-FPBA-COF shell acts as a hydrophobic "shield", which not only improves the hydrophobicity and stability of hydrophilic NH2-MIL-101(Fe), but also makes the extraction efficiency of flavonoids from MOF@COF composite significantly higher than that of pure NH2-MIL-101(Fe) and TAPB-FPBA-COF. In addition, a sensitive analytical method with excellent linearities (0.1-500 ng mL-1, R2 ≥ 0.9967), low limits of detection (0.02-0.04 ng mL-1 for water; 0.04-0.07 ng mL-1 for grape juice; 0.06-0.08 ng mL-1 for honey), good repeatability (intra-day/inter-day precision are 1.86-5.37%/1.82-7.79%, respectively) and only 5 mg of adsorbent per cartridge was established by optimizing the SPE process combined with high performance liquid chromatography with ultraviolet-visible detector (HPLC-UV). Meanwhile, selectivity study and comparative experiments with the commercial C18 adsorbent showed that the MOF@COF adsorbent exhibited satisfactory extraction efficiency for flavonoids due to multiple interactions such as hydrogen bonding, hydrophobic, and π-π interactions. Finally, the good recoveries in grape juice (84.5-102.5%) and honey (87.5-104.6%) samples further validated the applicability of the proposed method in complex samples.

Novel Pickering emulsion gels stabilized solely by phenylalanine amidated pectin: Characterization, stability and curcumin bioaccessibility.

Pickering emulsion gels represent a novel class of non-toxic and biocompatible emulsions, offering extensive applications in the pharmaceutical and food additive sectors. This study delineates the synthesis of Pickering emulsion gels utilizing native and amidated pectin samples. Phenylalanine amidated pectin (AP) was procured via an ultra-low temperature enzyme method, while the control group (LP) adhered to an identical procedure without papain catalysis. Experimental outcomes revealed that the AP Pickering emulsion gel manifested superior stability compared to pectin emulsion samples (PE and LP). The Pickering emulsion gel from 5 % amidated pectin (5AP) retained stability throughout a 14-day emulsion stability assessment. Furthermore, all emulsion samples were evaluated for their capacity to deliver and sustain curcumin within an in vitro digestion simulation. Rheological properties and oil droplet size results indicated that the 5AP Pickering emulsion gel exhibited optimal cream index and emulsion stability, effectively inhibiting premature water-oil stratification within the emulsion and augmenting curcumin bioaccessibility. Within the in vitro digestion simulation, the 5AP Pickering emulsion gel demonstrated the highest curcumin bioaccessibility, measured at 17.96 %.

Effects of Aire on perforin expression in BMDCs via TLR7/8 and its therapeutic effect on type 1 diabetes.

AIMS: Type 1 diabetes, as a kind of autoimmune diseases, usually results from the broken-down of self-tolerance. Autoimmune regulator (Aire), as a transcription factor, induces peripheral tolerance by regulating Toll-like receptor (TLR) expression in dendritic cells (DCs). Several studies have recently identified a small population of perforin-expressing DCs, which is an important population of tolerogenic DCs (tolDCs) that restricts autoreactive T cells in vivo through a perforin-mediated mechanism. Thus, the present study explored the specific relationship among Aire, perforin-expressing DCs and immune tolerance, as well as their roles in type 1 diabetes. METHODS: We conducted studies based on the Aire-overexpressing bone marrow-derived dendritic cell (BMDC) model. And through in vitro and in vivo experiments to observe that Aire-overexpressing BMDCs which express perforin induce immune tolerance and treat type 1 diabetes via TLR7/8. RESULTS: Aire enhances the expression of perforin in BMDCs after treatment with the TLR7/8 ligand as well as promotes the expression of TLR7/8 and myeloid differentiation primary response gene 88 (MyD88)-dependent pathway molecules. Aire-overexpressing BMDCs mediate apoptosis of allogeneic CD8+ T cells via perforin in vitro. Moreover, Aire-overexpressing BMDCs enhance the therapeutic effect of type 1 diabetes in non-obese diabetic (NOD) mice via perforin and induce apoptosis of autoreactive CD8+ T cells in vivo. CONCLUSIONS: These results provide an experimental basis for comprehensively elucidating the role and significance of Aire expression in peripheral DCs, thereby providing new ideas for the treatment of autoimmune diseases by using Aire as a target to induce the production of perforin-expressing DCs.

One-step fabrication of hydrophobic metal-organic framework@covalent organic framework hybrid as sorbent for high-performance solid-phase extraction of flavonoids.

Metal-organic framework (MOF) and covalent organic framework (COF) exhibit excellent extraction performance in sample pretreatment, but their wider application is hindered by some inherent drawbacks. Herein, we successfully synthesized a novel MOF@COF hybrid material with large specific surface area, good chemical stability and reusability, which is suitable as a solid phase extraction (SPE) sorbent for the efficient extraction of flavonoids. Importantly, due to the synergistic effect, the obtained MOF@COF hybrid material showing a higher extraction efficiency than individual MOF and COF. This is mainly due to the obtained MOF@COF hybrid material combines the high specific surface area of MOF and multiple interactions (hydrophobic interaction, hydrogen bonding and π-π stacking interaction) with flavonoids conferred by the COF structure. Then, a sensitive analytical method for flavonoids with ideal linear range (1-500 ng mL-1), low detection limit (0.15-0.41 ng mL-1) and good repeatability (2.64-6.20%) was developed under optimized conditions. In addition, the MOF@COF hybrid sorbent has better selectivity for hydrophobic targets containing multiple hydrogen bond acceptors/donors. Finally, the established method was applied to the determination of flavonoids in different food samples, and satisfactory recoveries (81.4-102.1%) were obtained, which initially confirmed its applicability.

Extraction of benzoylurea insecticides from tea leaves based on thermoplastic polyethyleneimine embedded magnetic nanoparticle carbon materials.

A novel mosaic structured core-shell composite, Silica@C/Ni (Sil@C/Ni), has been prepared by embedding Ni nanoparticles on the surface of silica microspheres via coordination and carbonization reduction, and was used as magnetic solid-phase extraction sorbents in combination with high performance liquid chromatography (HPLC) for the extraction and determination of four benzoylurea insecticides (BUs) in tea leaves. Based on the fact that hydrogen bonding and hydrophobic interactions exist between the material and BUs, allowing BUs on the surface of the material can achieve rapid mass transfer and improved sorption performance, satisfactory extraction recoveries have been achieved in practical sample applications. Under the optimized experimental conditions, the linear ranges were 0.5-200 µg L-1 for diflubenzuron and triflumuron, 1.0-200 µg L-1 for teflubenzuron and 0.8-200 µg L-1 for flufenoxuron with the correlation coefficients R2 ≥ 0.9991. The method has limits of detection and limits of quantification of 0.2-0.4 µg L-1 and 0.5-1.0 µg L-1, respectively. The intra-day and inter-day relative standard deviations were less than 5%. The actual sample recoveries were 76.63-95.26%. In addition, Sil@C/Ni was used repeatedly for 15 times and still showed a relatively satisfactory recovery of the four BUs. Therefore, Sil@C/Ni has a high stability and can be used as an ideal magnetic solid phase extraction sorbent for the trace enrichment of BUs in tea-leaf samples.

TiO2@MOF-919(Fe-Cu) as a sorbent for the extraction of benzoylurea pesticides from irrigation water and fruit juices.

The TiO2@MOF-919(Fe-Cu) solid-phase extraction material was prepared by growing MOF-919(Fe-Cu) in situ on three-dimensional radial TiO2 microspheres by a simple solvothermal method. This combination drew on both the resources of good single dispersion and extraction rate, which made it a better extraction material. It was accompanied with high-performance liquid chromatography (SPE-HPLC) for the separation and determination of four benzoylurea pesticides (triflumuron, chlorbenzuron, teflubenzuron and diflubenzuron) in afforestation irrigation water and juice samples (grape, peach and apple juices). Under the optimal conditions, the linearity of the method ranged from 1 to 400 µg L-1 with a correlation coefficient (R2) ≥ 0.9994, while the detection limit was in the range of 0.40-0.56 µg L-1 for the four pesticides. The adopted material showed good reusability and can be used no less than 10 times. The intra-day and inter-day precision were in the range of 1.78-3.24% and 4.06-5.08%, respectively. The proposed method was then successfully applied for the detection of benzoylurea pesticides in the spiked samples with good recoveries (72.3-108.4%) and good precision (5.15%) due to π-π and hydrophobic interactions between the analytes and adsorbent. The results show that the composite had the potential to be used as a SPE adsorbent for the enrichment and extraction of benzene ring structures containing imide groups in actual samples.

STIM1 Deficiency In Intestinal Epithelium Attenuates Colonic Inflammation and Tumorigenesis by Reducing ER Stress of Goblet Cells.

BACKGROUND & AIMS: As an indispensable component of store-operated Ca2+ entry, stromal interaction molecule 1 (STIM1) is known to promote colorectal cancer and T-cell-mediated inflammatory diseases. However, whether the intestinal mucosal STIM1 is involved in inflammatory bowel diseases (IBDs) is unclear. This study aimed to investigate the role of intestinal epithelial STIM1 in IBD. METHODS: Inflammatory and matched normal intestinal tissues were collected from IBD patients to investigate the expression of STIM1. Intestinal epithelium-specific STIM1 conditional knockout mice (STIM1ΔIEC) were generated and induced to develop colitis and colitis-associated colorectal cancer. The mucosal barrier, including the epithelial barrier and mucus barrier, was analyzed. The mechanisms by which STIM1 regulate goblet cell endoplasmic reticulum stress and apoptosis were assessed. RESULTS: STIM1 could regulate intestinal epithelial homeostasis. STIM1 was augmented in the inflammatory intestinal tissues of IBD patients. In dextran sodium sulfate-induced colitis, STIM1 deficiency in intestinal epithelium reduced the loss of goblet cells through alleviating endoplasmic reticulum stress induced by disturbed Ca2+ homeostasis, resulting in the maintenance of the integrated mucus layer. These effects prevented commensal bacteria from contacting and stimulating the intestinal epithelium of STIM1ΔIEC mice and thereby rendered STIM1ΔIEC mice less susceptible to colitis and colitis-associated colorectal cancer. In addition, microbial diversity in dextran sodium sulfate-treated STIM1ΔIEC mice slightly shifted to an advantageous bacteria, which further protected the intestinal epithelium. CONCLUSIONS: Our results establish STIM1 as a crucial regulator for the maintenance of the intestinal barrier during colitis and provide a potential target for IBD treatment.

Core-shell MOFs-based composites of defect-functionalized for mixed-mode chromatographic separation.

The micropores of the metal-organic frameworks (MOFs) endow with the advantages of size selectivity and large specific surface area, etc., but they limit their applications toward the control of diffusion and transport processes. Here, we report a strategy to prepare the hierarchical porous material, functional defect, which allows incorporation of L-Cysteine in the MOF by defect-loading. Silica microspheres were modified with these materials to form core-shell composites and used as mixed-mode stationary phases for chromatographic separations. Compared with the traditional MOFs-based stationary phase, it exhibited superior efficiency and selectivity for separation of various analytes and highlighted the role of defect of MOFs and function of L-Cysteine. In addition to the rapid separation of hydrophobic compounds, the stationary phase showed great potential in the separation of hydrophilic analytes, especially for separation of ten carbohydrates and eight sulfonamides. It showed excellent chromatographic reproducibility and stability, and the repeatability of preparation was investigated by relative standard deviations of retention time and/or column efficiency of objective compounds, which was among different batches less than 1.81%. This demonstration provided deep understanding of separation mechanism between MOF-based composites with functional defect and analytes, and stimulated the wide applications of such defective MOFs complexes in separations and analysis.

The roles of transmembrane family proteins in the regulation of store-operated Ca2+ entry.

Store-operated Ca2+ entry (SOCE) is a major pathway for calcium signaling, which regulates almost every biological process, involving cell proliferation, differentiation, movement and death. Stromal interaction molecule (STIM) and ORAI calcium release-activated calcium modulator (ORAI) are the two major proteins involved in SOCE. With the deepening of studies, more and more proteins are found to be able to regulate SOCE, among which the transmembrane (TMEM) family proteins are worth paying more attention. In addition, the ORAI proteins belong to the TMEM family themselves. As the name suggests, TMEM family is a type of proteins that spans biological membranes including plasma membrane and membrane of organelles. TMEM proteins are in a large family with more than 300 proteins that have been already identified, while the functional knowledge about the proteins is preliminary. In this review, we mainly summarized the TMEM proteins that are involved in SOCE, to better describe a picture of the interaction between STIM and ORAI proteins during SOCE and its downstream signaling pathways, as well as to provide an idea for the study of the TMEM family proteins.