Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma.

Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP3) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.

Assessing food availability and healthier options in an urban Chinese university: a case study using the Chinese Nutrition Environment Measurement Survey for Stores (C-NEMS-S).

Young adults (18-24 years) in universities are frequently exposed to an environment that promotes unhealthy eating behaviors. Using a validated tool, the Chinese Nutrition Environment Measurement Survey for Stores (C-NEMS-S), we assess the food availability and healthier options in a large, urban Chinese university. We employed C-NEMS-S for scoring criteria and weighting. A total of 52 on-campus canteen outlets were audited in an urban university located in Shijiazhuang City, China. General food outlets (n 43) and self-served food outlets (n 7) were further categorized into eight subtypes. Beverage outlets (n 2) were discussed separately from food outlets. C-NEMS-S scores were significantly different across food outlet types (P = 0.0024), especially between noodle and rice outlets (P = 0.0415). Food availability scores for starchy tubers (P < 0.001), dry beans (P < 0.001), vegetables (P = 0.0225), and fruits (P < 0.001) were significantly different across food outlet subtypes. Healthier options were scarce and only appeared in "grains" (n 2) and "meat and poultry" (n 2) categories. Further research on improving the accustomed audit tool and assessing university student diet quality is warranted.

A disintegrin and metalloproteinase 22 activates integrin ß1 through its disintegrin domain to promote the progression of pituitary adenoma.

BACKGROUND: Approximately 35% of pituitary adenoma (PA) display an aggressive profile, resulting in low surgical total resection rates, high recurrence rates, and worse prognosis. However, the molecular mechanism of PA invasion remains poorly understood. Although "a disintegrin and metalloproteinases" (ADAMs) are associated with the progression of many tumors, there are no reports on ADAM22 in PA. METHODS: PA transcriptomics databases and clinical specimens were used to analyze the expression of ADAM22. PA cell lines overexpressing wild-type ADAM22, the point mutation ADAM22, the mutated ADAM22 without disintegrin domain, and knocking down ADAM22 were generated. Cell proliferation/invasion assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, mass spectrometry, Reverse transcription-quantitative real-time PCR, phos-tag SDS-PAGE, and Western blot were performed for function and mechanism research. Nude mice xenograft models and rat prolactinoma orthotopic models were used to validate in vitro findings. RESULTS: ADAM22 was significantly overexpressed in PA and could promote the proliferation, migration, and invasion of PA cells. ADAM22 interacted with integrin ß1 (ITGB1) and activated FAK/PI3K and FAK/ERK signaling pathways through its disintegrin domain to promote PA progression. ADAM22 was phosphorylated by PKA and recruited 14-3-3, thereby delaying its degradation. ITGB1-targeted inhibitor (anti-itgb1) exerted antitumor effects and synergistic effects in combination with somatostatin analogs or dopamine agonists in treating PA. CONCLUSIONS: ADAM22 was upregulated in PA and was able to promote PA proliferation, migration, and invasion by activating ITGB1 signaling. PKA may regulate the degradation of ADAM22 through post-transcriptional modification levels. ITGB1 may be a potential therapeutic target for PA.

Corn peptides attenuate non-alcoholic fatty liver disease via PINK1/Parkin-mediated mitochondrial autophagy.

Background: Corn peptides, a novel food prepared from corn gluten meal (CGM) by enzymatic hydrolysis or microbial fermentation, have attracted considerable interest owing to their various bioactive properties. However, the underlying mechanism of corn peptides attenuate non-alcoholic fatty liver disease (NAFLD) remains unclear. Objective: This study aimed to investigate the effect of corn peptides in NAFLD and to decipher the underlying mechanisms. Design: NAFLD was induced by a high-fat diet (HFD) for 10 weeks. Corn peptides were administered during the period. Human hepatocellular carcinomas (HepG2) cells induced by free fatty acids were used for this mechanism study. Results: Corn peptides alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, corn peptides blocked mitophagy suppression by HFD based on the increased LC3, ATG7 expressions, as well as decreased P62 levels. Corn peptides increased the expression of proteins involved in fatty acid ß-oxidation, such as PPARα and PGC-1α. Corn peptides also improved the Ser/Thr kinase PINK1 (PINK1) and the E3 ubiquitin ligase Parkin (Parkin) translocation to mitochondria, which is confirmed by immunofluorescence. Furthermore, stable knockdown of PINK1 by PINK1 SiRNA in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Conclusion: Corn peptides improved cell injury and ameliorated mitochondrial dysfunction and lipid accumulation via PINK1/Parkin-mediated autophagy in NAFLD. Thus, corn peptides could be a promising nutritional molecule with natural functions for preventing NAFLD.

Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway.

TAF participated in the progression of various cancers, including PA via the release of soluble factors. Exosomes belonged to extracellular vesicles, which were revealed as a crucial participator in intercellular communication. However, the expression pattern and effect of TAF-derived exosomes remained largely unknown in PA. In the present study, we performed in silico analysis based on public RNA-seq datasets to generate the circRNA/miRNA regulatory network. The qRT-PCR, Western blotting, RNA pull-down, and luciferase assay were performed to investigate the effect of TAF-derived exosomes. TAF-derived exosomal circDennd1b was significantly upregulated in PA and promoted the proliferation, migration, and invasion of PA cells via sponging miR-145-5p in PA cells. In addition, miR-145-5p directly regulated One Cut homeobox 2 (ONECUT2/OC2) expression and inhibited the promoting effect of ONECUT2 on PA. We further demonstrated that ONECUT2 transcriptionally increased fibroblast growth factor receptor 3 (FGFR3) expression, which further activates the mitogen-activated protein kinases (MAPK) pathway, thus promoting PA progression. Moreover, the suppression of TAFs by ABT-263 and ONECUT2 by CSRM617 inhibited the growth of PA. In conclusion, our study illustrated that TAF-derived exosomal circDennd1b affected PA progression via regulating ONECUT2 expression, which provides a potential therapeutic strategy against aggressive PA.

Nutritional support for perioperative patients in China: progress with ERAS.

The prevalence of malnutrition in surgical patients is high, particularly in elderly, oncologic, critically ill and morbidly obese patients. In recent years, as the concept of enhanced recovery after surgery (ERAS) has gained in popularity, the concept and strategy of nutritional care for surgical patients has also evolved. The concept of nutritional management is relatively new in surgical patient management, which promotes integrating the "nutritional screening-assessment-diagnosis-treatment" (NSADT) scheme into the preoperative, intraoperative, postoperative, and post-discharge processes of disease treatment and rehabilitation. This article will review the practice of perioperative nutrition management in surgical patients in China.

PKCθ Regulates Pituitary Adenoma Bone Invasion by Activating Osteoclast in NF-κB/IL-1ß-Dependent Manner.

BACKGROUND: Pituitary adenoma (PA) bone invasion results in adverse outcomes, such as reduced rates of complete surgical resection and biochemical remission as well as increased recurrence rates, though few studies have been conducted. METHODS: We collected clinical specimens of PAs for staining and statistical analysis. Evaluation of the ability of PA cells to induce monocyte-osteoclast differentiation by coculturing PA cells with RAW264.7 in vitro. An in vivo model of bone invasion was used to simulate the process of bone erosion and evaluate the effect of different interventions in alleviating bone invasion. RESULTS: We found an overactivation of osteoclasts in bone-invasive PAs and concomitant aggregation of inflammatory factors. Furthermore, activation of PKCθ in PAs was established as a central signaling promoting PA bone invasion through the PKCθ/NF-κB/IL-1ß pathway. By inhibiting PKCθ and blocking IL1ß, we were able to significantly reverse bone invasion in an in vivo study. Meanwhile, we also found that celastrol, as a natural product, can obviously reduce the secretion of IL-1ß as well as alleviate the progression of bone invasion. CONCLUSIONS: By activating the PKCθ/NF-κB/IL-1ß pathway, pituitary tumors are able to induce monocyte-osteoclast differentiation in a paracrine manner and promote bone invasion, which can be alleviated by celastrol.

Effect of unicompartmental knee arthroplasty combined with arthroscopic debridement on knee osteoarthritis and analysis of risk factors of deep venous thrombosis.

OBJECTIVE: To analyze the clinical effect of unicompartmental knee arthroplasty combined with arthroscopic debridement on knee osteoarthritis and the risk factors leading to deep venous thrombosis (DVT). METHODS: Data of 110 patients with knee osteoarthritis admitted to The People's Hospital of Wenjiang Chengdu for surgical treatment from February 2019 to June 2021 were retrospectively analyzed. According to the surgical treatment methods, 58 patients treated with unicompartmental knee arthroplasty were included in the control group. The remaining 52 patients with combined treatment of unicompartmental knee arthroplasty and arthroscopic knee debridement were included in the observation group. The therapeutic effect, knee joint function score, Visual Analogue Scale (VAS) score, time required for knee flexion of 90°, length of hospital stay, and incidence of postoperative DVT were compared between the two groups 1 month after the operation. Risk factors leading to the development of DVT were analyzed. RESULTS: One month after the operation, the overall response rate, knee joint function score, and VAS score in the observation group were significantly better than those in the control group. The time required for knee flexion of 90° and length of hospital stay were shorter and the incidence of DVT was lower in the observation group than those in the control group. According to the occurrence of DVT, patients were divided into a DVT group and a non-DVT group. The univariate analysis revealed that age, body mass index, history of diabetes, coagulation parameters, and surgical methods were related to the occurrence of DVT. The logistics regression analysis revealed that age, body mass index, coagulation parameters, and surgical methods were independent risk factors affecting the occurrence of postoperative DVT. CONCLUSION: The combined treatment of unicompartmental knee arthroplasty and arthroscopic debridement can significantly improve knee joint function and bone metabolism and reduce the incidence of postoperative DVT of patients with knee osteoarthritis, achieving a more satisfactory therapeutic effect.

How Does the University Food Environment Impact Student Dietary Behaviors? A Systematic Review.

The food environment has been implicated in creating an obesogenic generation; and while previous research has focused on population-wide initiatives, the university population resides in a research gap. To explore detailed components of the university food environment and what shaped dietary behaviors, we retrieved literature from the following databases: ScienceDirect, Scopus, PubMed, Medline, and EMBASE. Eleven studies were identified for qualitative content analysis and study quality assessment identified most of the studies as of good quality (n 8) and some as of fair quality (n 3). The certainty of evidence remained at a low level for all (n 11) studies due to the cross-sectional, observational nature of studies. Three major themes emerged: (1) food environment, (2) student perceptions (SPs), and (3) dietary outcome (DO). In a university food environment, the taste of food was paramount for the food choices of students, followed by the availability of food and the price of food. When university students perceive and choose foods and beverages, they sometimes regard unhealthy foods and beverages as healthy options. The diet quality of university students is more susceptible to living arrangements and socioeconomic status, but higher salt, fat, and added sugar consumption generally resulted in poorer quality of diet on campus. Future research could use novel methods to explore a wider range and deeper level of students' dietary behavior determinants in university food environments. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021283562.

PltDB: a blood platelets-based gene expression database for disease investigation.

MOTIVATION: Molecular profiling of blood-based liquid biopsies is a promising disease detection method, which overcomes the limitations of invasive diagnostic strategies. Recently, gene expression profiling of platelets reportedly provides valuable resource for developing new biomarkers for the detection of diseases, including cancer. However, there is no database containing RNAs in platelets. RESULTS: In this study, we constructed PltDB (http://www.pltdb-hust.com), a blood platelets-based gene expression database featuring integration and visualization of RNA expression profiles based on RNA-seq and microarray data spanning both normal individuals and patients with different diseases. PltDB currently contains the expression landscape of mRNAs, lncRNAs, circRNAs and miRNAs in platelets from patients with different disease types and healthy controls. Moreover, PltDB provides users with the tools for visualizing results of comparison and correlation analysis and for downloading expression profiles and analysis results. A submission interface for the scientific community is also embraced for uploading novel RNA expression profiles derived from platelet samples. PltDB will offer a comprehensive review of the clinical use of platelets, overcome technical problems when analyzing data from diverse studies and serve as a powerful platform for developing new blood biomarkers. AVAILABILITY AND IMPLEMENTATION: PltDB is accessible at http://www.pltdb-hust.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Current landscape of tumor-derived exosomal ncRNAs in glioma progression, detection, and drug resistance.

Glioma is the most common and fatal tumor of the central nervous system in humans. Despite advances in surgery, radiotherapy, and chemotherapeutic agents, glioma still has a poor prognosis. The tumor microenvironment (TME) of glioma is of highly complex heterogeneity, which relies on a network-based communication between glioma cells and other stromal cell types. Exosomes are the most common type of naturally occurring extracellular vesicles, ranging in size from 40 to 160 nm, and can serve as carriers for proteins, RNAs, and other biologically active molecules. Recent evidence has shown that glioma-derived exosomes (GDEs) can be integrally detected in the local tissue and circulatory blood samples, and also can be transferred to recipient cells to mediate transmission of genetic information. Non-coding RNAs (ncRNAs) mainly including microRNA, long non-coding RNA, and circular RNA, account for a large portion of the human transcriptome. A broad range of ncRNAs encapsulated in GDEs is reported to exert regulatory functions in various pathophysiological processes of glioma. Herein, this review summarizes the latest findings on the fundamental roles of GDE ncRNAs that have been implicated in glioma behaviors, immunological regulation, diagnosis potential, and treatment resistance, as well as the current limitations and perspectives. Undoubtedly, a thorough understanding of this area will provide comprehensive insights into GDE-based clinical applications for combating gliomas.

The regulators of BCR signaling during B cell activation.

B lymphocytes produce antibodies under the stimulation of specific antigens, thereby exerting an immune effect. B cells identify antigens by their surface B cell receptor (BCR), which upon stimulation, directs the cell to activate and differentiate into antibody generating plasma cells. Activation of B cells via their BCRs involves signaling pathways that are tightly controlled by various regulators. In this review, we will discuss three major BCR mediated signaling pathways (the PLC-γ2 pathway, PI3K pathway and MAPK pathway) and related regulators, which were roughly divided into positive, negative and mutual-balanced regulators, and the specific regulators of the specific signaling pathway based on regulatory effects.

The Role of Mst1 in Lymphocyte Homeostasis and Function.

The Hippo pathway is an evolutionarily conserved pathway crucial for regulating tissue size and for limiting cancer development. However, recent work has also uncovered key roles for the mammalian Hippo kinases, Mst1/2, in driving appropriate immune responses by directing T cell migration, morphology, survival, differentiation, and activation. In this review, we discuss the classical signaling pathways orchestrated by the Hippo signaling pathway, and describe how Mst1/2 direct T cell function by mechanisms not seeming to involve the classical Hippo pathway. We also discuss why Mst1/2 might have different functions within organ systems and the immune system. Overall, understanding how Mst1/2 transmit signals to discrete biological processes in different cell types might allow for the development of better drug therapies for the treatments of cancers and immune-related diseases.

The Coordination Between B Cell Receptor Signaling and the Actin Cytoskeleton During B Cell Activation.

B-cell activation plays a crucial part in the immune system and is initiated via interaction between the B cell receptor (BCR) and specific antigens. In recent years with the help of modern imaging techniques, it was found that the cortical actin cytoskeleton changes dramatically during B-cell activation. In this review, we discuss how actin-cytoskeleton reorganization regulates BCR signaling in different stages of B-cell activation, specifically when stimulated by antigens, and also how this reorganization is mediated by BCR signaling molecules. Abnormal BCR signaling is associated with the progression of lymphoma and immunological diseases including autoimmune disorders, and recent studies have proved that impaired actin cytoskeleton can devastate the normal activation of B cells. Therefore, to figure out the coordination between the actin cytoskeleton and BCR signaling may reveal an underlying mechanism of B-cell activation, which has potential for new treatments for B-cell associated diseases.

A superhydrophobic sponge with excellent absorbency and flame retardancy.

Frequent oil spillages and the industrial discharge of organic solvents have not only caused severe environmental and ecological damage, but also create a risk of fire and explosion. Therefore, it is imperative, but also challenging, to find high-performance absorbent materials that are both effective and less flammable. Here we present a superior superhydrophobic sponge that exhibits excellent absorption performance through a combination of its superhydrophobicity, high porosity, and robust stability. More importantly, it inherits the intrinsic flame-retardant nature of the raw melamine sponge, and is thus expected to reduce the risk of fire and explosion when being used as an absorbent for flammable oils and organic compounds. Moreover, the fabrication of this sponge is easy to scale up, since it does not use a complicated process or sophisticated equipment. These characteristics make the sponge a much more competitive product than the commercial absorbent, nonwoven polypropylene fabric.

[Chemical constituents of Conioselinum vaginatum].

Sixteen compounds were isolated from Conioselinum vaginatum by silica column chromatography over silica gel and Sephadex LH-20, as well as recrystallization. On the basis of their physical and chemical properties and spectral data, their structures were identified as ligustilide (1), 1,3-dilinolein (2), coniferaldehyde (3), myristicin (4), stigmasterol (5), beta-sitosterol (6), vanillin (7), pregnenolone (8), bergapten (9), xanthotoxin (10), methyl indole-3-carboxylate (11), ferulic acid (12), (E)-3-methoxy-4,5-methylenedioxy-cinnamic alcohol (13), p-hydroxybenzaldehyde (14), 3-methoxy-4,5-methylenedioxy-acetophenone (15), and alpha-(ethoxymethyl)-4-hydroxy- benzenemethanol (16). Among them, compound 15 was a new natural product, and compounds 2, 3, 10, 11, 14, and 16 were obtained from this genus for the first time.

[Chemical constituents of petroleum ether extract of fruits of Schisandra sphenanthera].

OBJECTIVE: To study the chemical constituents in the fruits of Schisandra sphenanthera. METHOD: The constituents were isolated by their silica gel column, Sephadex LH-20 gel column, and their structures were elucidated by their chemical properties and spectroscopic analyses. RESULT: Twelve compounds were isolated and identified as (+)-anwulignan (1), deoxyschizandrin (2), interiotherin A (3), schisantherin A (4), beta-sitosterol (5), schisantherin D (6), 4-hydroxybenzaldehyde (7), 6-O-benzoylgomisin O (8), schizandronic acid (9), schisanlactone D (10), schisanlactone B (11), kadsulactone A (12). CONCLUSION: Compounds 3, 7, 10-12 were obtained from this plant for the first time.

Facile synthesis and up-conversion properties of monodisperse rare earth fluoride nanocrystals.

Monodisperse rare earth (RE) fluoride colloidal nanocrystals (NCs) including REF(3) (RE = La, Pr, Nd), NaREF(4) (RE = Sm-Ho, Y) and Na(5)RE(9)F(32) (RE = Er, Yb, Lu) have been successfully synthesized by a facile one-step method using oleic acid as surfactant and 1-octadecene as solvent. The phase, morphology, size, and photoluminescence properties of as-synthesized NCs were well investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FT-IR), and photoluminescence (PL) spectra. The results reveal that the as-synthesized NCs consist of monodisperse colloidal NCs with narrow size distribution, which can easily disperse in non-polar cyclohexane solvent. The as-prepared NCs exhibit a rich variety of morphologies and different crystal phases (hexagonal or cubic), which may be related to the inherent natures of different rare earth ions. The possible formation mechanism of NCs with diverse architectures has been presented. In addition, representative Yb/Er, Yb/Tm, or Yb/Ho co-doped NaGdF(4) and Na(5)Lu(9)F(32) NCs exhibit intensive multicolor up-conversion (UC) luminescence under a single 980 nm NIR excitation, displaying potential applications in bioimaging and therapy. Moreover, transparent and UC fluorescent NCs-polydimethylsiloxane (PDMS) composites with regular dimensions were also prepared by an in situ polymerization route.

Chemical analysis of twelve lignans in the fruit of Schisandra sphenanthera by HPLC-PAD-MS.

The fruit of S. sphenanthera, known as "Nanwuweizi", has been widely used as traditional Chinese medicine for several thousand years. However, the current determination methods are not sufficient to evaluate its quality. An accurate, sensitive and reliable high performance liquid chromatography coupled with photodiode array detection and mass spectrum (HPLC-PAD-MS) was developed for quantitative analysis of twelve lignans (schisandrol A, schisandrol B, gomisin G, schisantherin A, schisantherin D, schisanhenol, (+)-anwulignan, deoxyschisandrin, schisandrin B, schisandrin C, 6-O-benzoylgomisin O, and interiotherin A) in the fruit of S. sphenanthera. The chromatographic conditions and extraction procedures were optimized during the study. The identity of chromatographic peaks in the sample HPLC profiles was confirmed by comparing the retention time, ultraviolet (UV) spectra and MS data with reference compounds. The validated method was successfully used to determine the twelve lignans in the samples collected from different localities in China. The hierarchical clustering analysis (HCA) and principal components analysis (PCA) were successfully applied to the data of twelve lignans from the HPLC profiles in sixteen batches of the fruit of S. sphenanthera to discriminate the samples with different sources. Moreover, the results of the loading plot of the PCA indicated that schisantherin A, (+)-anwulignan, and deoxyshisandrin were found to be the main constituents in the fruit of S. sphenanthera, and which could be chosen as the chemical markers for evaluate the quality of the fruit of S. sphenanthera. The results indicated that the developed method was readily utilized as a quality evaluation method for the fruit of S. sphenanthera.

[Microscopic authentication method of traditional Chinese medicine Gusuibu].

OBJECTIVE: To provide practical method for microscopic authentication of traditional Chinese medicine Gusuibu and its adulterants. METHOD: By means of light microscope, scanning electron microscopy and tissue section techniques, the morphology, the size of the rhizome scales and their bearing position in the original plants of Gusuibu and its adulterants, i. e. Drynaria roosii, D. delavayi, D. quercifolia and Pseudodrynaria coronans were analyzed. RESULT: There were significant differences between scales length of D. roosii, D. delavayi and P. coronans, while there was no significant difference between that of D. roosii and D. quercifolia. The scale teeth of D. delavayi were usually curved, bifid and uneven distributed at the scale fringe, which was different from that of the other three species. The base of the scales sinks in epidermis in D. roosii, D. quercifolia, and P. coronans, while it bore at the raised part of epidermis in D. delavayi. CONCLUSION: [corrected] Morphology, size and bearing position of the rhizome scales have significant differences in the several species. Therefore, these characteristics can be applied to the identification of Gusuibu and its adulterants.