ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.

GPR37 promotes colorectal cancer against ferroptosis by reprogramming lipid metabolism via p38-SCD1 axis.

Colorectal cancer (CRC) is a prevalent malignant tumor worldwide, leading to significant morbidity and disease burden. Diagnostic indicators and treatment objectives for CRC are urgently needed. This study demonstrates that GPR37, a GPCR receptor, is highly expressed in CRC. Depletion of GPR37 significantly reduced CRC tumor cell growth both in vitro and in vivo. Further tests showed that GPR37 protects cancer cells from ferroptosis by upregulating SCD1 expression, thereby modulating lipid metabolism, suppressing the level of reactive oxygen species, and mitigating ferroptosis. Mechanistic studies have shown that GPR37 modulates lipid metabolism in tumor cells by promoting SCD1 transcription via the MAPK-p38 signaling pathway. Our results reveal the pro-carcinogenic effect of GPR37 in primary CRC and suggest that targeting GPR37 could be a potential therapeutic target for CRC.

Integrative bioinformatics analysis for identifying the mitochondrial-related gene signature associated with immune infiltration in premature ovarian insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of ovarian function before the age of 40. Although mitochondrial dysfunction and immune disorders are believed to contribute to ovarian damage in POI, the interplay between these factors remains understudied. METHODS: In this research, transcriptomic data related to POI were obtained from the NCBI GEO database. Hub biomarkers were identified through the construction of a protein‒protein interaction (PPI) network and further validated using RT‒qPCR and Western blot. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. A comprehensive investigation of the mitochondrial and immune profiles of POI was carried out through correlation analysis. Furthermore, potential therapeutic agents were predicted utilizing the cMap database. RESULTS: A total of 119 mitochondria-related differentially expressed genes (MitoDEGs) were identified and shown to be significantly enriched in metabolic pathways. Among these genes, Hadhb, Cpt1a, Mrpl12, and Mrps7 were confirmed both in a POI model and in human granulosa cells (GCs), where they were found to accumulate in GCs and theca cells. Immune analysis revealed variations in macrophages, monocytes, and 15 other immune cell types between the POI and control groups. Notably, strong correlations were observed between seven hub-MitoDEGs (Hadhb, Cpt1a, Cpt2, Mrpl12, Mrps7, Mrpl51, and Eci1) and various functions, such as mitochondrial respiratory complexes, dynamics, mitophagy, mitochondrial metabolism, immune-related genes, and immunocytes. Additionally, nine potential drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, and pizotifen) targeting key genes were identified. CONCLUSIONS: Our results highlight the crosstalk between mitochondrial function and the immune response in the development of POI. The identification of MitoDEGs could lead to reliable biomarkers for the early diagnosis, monitoring, and personalized treatment of POI.

m6A-modified RIPK4 facilitates proliferation and cisplatin resistance in epithelial ovarian cancer.

BACKGROUND: Cisplatin (DDP)-based chemotherapy is a common chemotherapeutic regimen for the treatment of advanced epithelial ovarian cancer (EOC). However, most patients rapidly develop chemoresistance. N6-methyladenosine (m6A) is a pervasive RNA modification, and its specific role and potential mechanism in the regulation of chemosensitivity in EOC remain unclear. METHODS: The expression of RIPK4 and its clinicopathological impact were evaluated in EOC cohorts. The biological effects of RIPK4 were investigated using in vitro and in vivo models. RNA m6A quantification was used to measure total m6A levels in epithelial ovarian cancer cells. Luciferase reporter, MeRIP-qPCR, RIP-qPCR and actinomycin-D assays were used to investigate RNA/RNA interactions and m6A modification of RIPK4 mRNA. RESULTS: We demonstrated that RIPK4, an upregulated mRNA in EOC, acts as an oncogene in EOC cells by promoting tumor cell proliferation and DDP resistance at the clinical, database, cellular, and animal model levels. Mechanistically, METTL3 facilitates m6A modification, and YTHDF1 recognizes the specific m6A-modified site to prevent RIPK4 RNA degradation and upregulate RIPK4 expression. This induces NF-κB activation, resulting in tumor growth and DDP resistance in vitro and in vivo. CONCLUSIONS: Collectively, the present findings reveal a novel mechanism underlying the induction of DDP resistance by m6A-modified RIPK4, that may contribute to overcoming chemoresistance in EOC.

Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis.

Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H2O2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO3 axis regulation, providing a possible therapeutic target for patients with POF.

Reason and control strategy for denitrification and anammox sludge flotation in nitrogen removal process: Mechanisms, strategies and perspectives.

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles.

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis.

BACKGROUND: Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated ß-gal (SA-ß-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed. RESULTS: Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition. CONCLUSION: H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.

Multiplex fluorescent amplification-refractory mutation system PCR method for the detection of 10 genetic defects in Holstein cattle and its comparison with the KASP genotyping assay.

The common deleterious genetic defects in Holstein cattle include haplotypes 1-6 (HH1-HH6), haplotypes for cholesterol deficiency (HCD), bovine leukocyte adhesion deficiency (BLAD), complex vertebral malformation (CVM) and brachyspina syndrome (BS). Recessive inheritance patterns of these genetic defects permit the carriers to function normally, but homozygous recessive genotypes cause embryo loss or neonatal death. Therefore, rapid detection of the carriers is essential to manage these genetic defects. This study was conducted to develop a single-tube multiplex fluorescent amplification-refractory mutation system (mf-ARMS) PCR method for efficient genotyping of these 10 genetic defects and to compare its efficiency with the kompetitive allele specific PCR (KASP) genotyping assay. The mf-ARMS PCR method introduced 10 sets of tri-primers optimized with additional mismatches in the 3' end of wild and mutant-specific primers, size differentiation between wild and mutant-specific primers, fluorescent labeling of universal primers, adjustment of annealing temperatures and optimization of primer concentrations. The genotyping of 484 Holstein cows resulted in 16.12% carriers with at least one genetic defect, while no homozygous recessive genotype was detected. This study found carrier frequencies ranging from 0.0% (HH6) to 3.72% (HH3) for individual defects. The mf-ARMS PCR method demonstrated improved detection, time and cost efficiency compared with the KASP method for these defects. Therefore, the application of mf-ARMS PCR for genotyping Holstein cattle is anticipated to decrease the frequency of lethal alleles and limit the transmission of these genetic defects.

Cytotoxic Compounds from Marine Fungi: Sources, Structures, and Bioactivity.

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.

Research on Image Mapping Spectrometer Based on Ultra-Thin Glass Layered Mapping.

The imaging quality of the Mapping Imaging Spectrometer (IMS) is crucial for spectral identification and detection performance. In IMS, the image mapper significantly influences the imaging quality. Traditional image mappers utilize a single-point diamond machining process. This process leads to inevitable edge eating phenomena that further results in noticeable deficiencies in imaging, impacting spectral detection performance. Therefore, we propose a manufacturing process for the image mapper based on ultra-thin layered glass. This process involves precision polishing of ultra-thin glass with two-dimensional angles, systematically assembling it into an image mapper. The surface roughness after coating is generally superior to 10 nm, with a maximum angle deviation of less than 3'. This results in high mapping quality. Subsequently, a principle verification experimental system was established to conduct imaging tests on real targets. The reconstructed spectrum demonstrates excellent alignment with the results obtained from the Computed Tomography Imaging Spectrometer (CTIS). We thereby validate that this approach effectively resolves the issues associated with edge eating (caused by traditional single-point diamond machining), and leads to improved imaging quality. Also when compared to other techniques (like two-photon polymerization (2PP)), this process demonstrates notable advantages such as simplicity, efficiency, low processing costs, high fault tolerance, and stability, showcasing its potential for practical applications.

The Protective Role of Interleukin 17A in Acinetobacter baumannii Pneumonia Is Associated with Candida albicans in the Airway.

Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17; P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%; P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g; P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU; P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g; P = 0.0313). In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%; P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.

A Practical Risk Classification of Early Recurrence in Hepatocellular Carcinoma Patients with Microvascular invasion after Hepatectomy: A Decision Tree Analysis.

PURPOSE: This study was designed to establish risk classifications for early recurrence in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. METHODS: The data of 563 HCC patients with MVI after hepatectomy from two hospitals were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse early recurrence. The risk classification for early recurrence was established by using classification and regression tree (CART) analysis and validated by using two independent validation cohorts from two hospitals. RESULTS: Multivariate analysis revealed that four indices, namely, infection of chronic viral hepatitis, MVI classification, tumour size, and serum alpha-fetoprotein (AFP), were independent prognostic factors for early recurrence in HCC patients with MVI. By CART analysis, MVI classification and serum AFP became the nodes of a decision tree and 3-stratification classifications that satisfactorily determined the risk of early recurrence were established. The area under the time-dependent receiver operating characteristic curve (AUC) values of the classification for early recurrence at 0.5, 1.0, and 2.0 years were 0.75, 0.73, and 0.71, respectively, which were all significantly higher than three common classic HCC stages (BCLC stage, Chinese stage, and TNM stage). The calibration curves showed good agreement between predictions by classification for early recurrence and actual survival outcomes. These prediction results also were confirmed in the independent internal and external validation cohorts. CONCLUSIONS: The 3 stratification classifications enabled satisfactory risk evaluation of early recurrence in HCC patients with MVI after hepatectomy.

LncRNA-EWSAT1 promotes hepatocellular carcinoma metastasis via activation of the Src-YAP signaling axis.

Regardless of the improvements in diagnostic and therapeutic methods, the clinical outcomes of hepatocellular carcinoma (HCC) patients remain poor. Although accumulating evidence indicates that lncRNAs (long noncoding RNAs) are essential within the control of tumorigenesis and the metastasis of cancer, the underlying mechanisms remain largely unknown. This work explored the pattern of expression and functional significance of a newly found lncRNA, Ewing sarcoma-associated transcript 1 (EWSAT1), in HCC metastasis. The results indicated that EWSAT1 was upregulated significantly in HCC relative to that in normal tissues and was correlated with an aggressive phenotype and low patient survival. Functional experiments demonstrated that EWSAT1 could promote proliferation and HCC cell metastasis both in vitro and in vivo. Mechanistically, EWSAT1 binds directly to Yes-associated protein (YAP), promotes Sarcoma gene (Src)-induced phosphorylation of YAP, facilitates nuclear translocation of YAP, and consequently, activates the transcription of Hippo-YAP signaling target genes involved in cancer evolution. This study found that EWSAT1 plays a crucial role in HCC metastasis and that it has the potential to be a prognosis biomarker and a target for therapeutics.

ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls.

PURPOSE: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging. METHODS: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions. RESULTS: NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients. CONCLUSION: Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.

Value and prognostic factors of repeat hepatectomy for recurrent colorectal liver metastasis.

BACKGROUND: More than 50% of patients with colorectal cancer develop liver metastases. Hepatectomy is the preferred treatment for resectable liver metastases. This review provides a perspective on the utility and relevant prognostic factors of repeat hepatectomy in recurrent colorectal liver metastasis (CRLM). DATA SOURCES: The keywords "recurrent colorectal liver metastases", "recurrent hepatic metastases from colorectal cancer", "liver metastases of colorectal cancer", "repeat hepatectomy", "repeat hepatic resection", "second hepatic resection", and "prognostic factors" were used to retrieve articles published in the PubMed database up to August 2020. Additional articles were identified by a manual search of references from key articles. RESULTS: Despite improvements in surgical methods and perioperative chemotherapy, recurrence remains common in 37%-68% of patients. Standards or guidelines for the treatment of recurrent liver metastases are lacking. Repeat hepatectomy appears to be the best option for patients with resectable metastases. The commonly reported prognostic factors after repeat hepatectomy were R0 resection, carcinoembryonic antigen level, the presence of extrahepatic disease, a short disease-free interval between initial and repeat hepatectomy, the number (> 1) and size (≥ 5 cm) of hepatic lesions, requiring blood transfusion, and no adjuvant chemotherapy after initial hepatectomy. The median overall survival after repeat hepatectomy ranged from 19.3 to 62 months, and the 5-year overall survival ranged from 21% to 73%. Chemotherapy can act as a test for the biological behavior of tumors with the goal of avoiding unnecessary surgery, and a multimodal approach involving aggressive chemotherapy and repeat hepatectomy might be the treatment of choice for patients with early recurrent CRLM. CONCLUSIONS: Repeat hepatectomy is a relatively safe and effective treatment for resectable recurrent CRLM. The presence or absence of prognostic factors might facilitate patient selection to improve short- and long-term outcomes.

TRIM14 Overexpression Induces Chemoresistance and Malignant Behaviors of Hepatocellular Carcinoma Cells by Activating the STAT3/HIF-1α Pathway.

Members of the tripartite motif (TRIM)-containing protein family have been found to be involved in the progression of hepatocellular carcinoma (HCC). TRIM14 exerts a promotive impact on several cancers. This study aimed to explore the function and mechanism of TRIM14 in HCC. TRIM14 expression in HCC tissues and HCC cell lines was detected. The overexpression or knockdown model of TRIM14 was established in HCC cell lines. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell assay, RT-PCR, Western blot, and immunofluorescence were performed to verify the influence of TRIM14 on cell proliferation, sensitivity to chemotherapy drugs, apoptosis, migration, invasion, and autophagy. A xenograft tumor model was used to confirm the impact of TRIM14 on tumor cell growth. As shown by the data, TRIM14 level was notably higher in the tumor tissues of HCC patients than in the adjacent tissues. The overall survival rate of patients with a high TRIM14 expression was relatively lower than that of patients with a low TRIM14 expression. TRIM14 upregulation enhanced the proliferation, autophagy, migration, and invasion of HCC cells and chemoresistant HCC cells and decreased apoptosis. TRIM14 knockdown contributed to the opposite effects. In in vivo experiments, TRIM14 upregulation bolstered tumor growth. Western blot analysis revealed that TRIM14 upregulation boosted signal transducer and activator of transcription3 (STAT3) and hypoxia-inducible factor-1alpha (HIF-1α) expression, and TRIM14 knockdown suppressed their expression. Moreover, repressing STAT3 and HIF-1α could mitigate the tumor-promoting role of TRIM14 in HCC cells. Overall, TRIM14 facilitated malignant HCC development and induced chemoresistance in HCC cells by activating the STAT3/HIF-1α axis.

miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer.

BACKGROUND: As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC. METHODS: MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model. RESULTS: We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3'-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107. CONCLUSIONS: These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.

Paraspinal Muscle in Chronic Low Back Pain: Comparison Between Standard Parameters and Chemical Shift Encoding-Based Water-Fat MRI.

BACKGROUND: Paraspinal musculature (PSM) is increasingly recognized as a contributor to low back pain (LBP), but with conventional MRI sequences, assessment is limited. Chemical shift encoding-based water-fat MRI (CSE-MRI) enables the measurement of PSM fat fraction (FF), which may assist investigations of chronic LBP. PURPOSE: To investigate associations between PSM parameters from conventional MRI and CSE-MRI and between PSM parameters and pain. STUDY TYPE: Prospective, cross-sectional. POPULATION: Eighty-four adults with chronic LBP (44.6 ± 13.4 years; 48 males). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted fast spin-echo and iterative decomposition of water and fat with echo asymmetry and least squares estimation sequences. ASSESSMENT: T1-weighted images for Goutallier classification (GC), muscle volume, lumbar indentation value, and muscle-fat index, CSE-MRI for FF extraction (L1/2-L5/S1). Pain was self-reported using a visual analogue scale (VAS). Intra- and/or interreader agreement was assessed for MRI-derived parameters. STATISTICAL TESTS: Mixed-effects and linear regression models to 1) assess relationships between PSM parameters (entire cohort and subgroup with GC grades 0 and 1; statistical significance α = 0.0025) and 2) evaluate associations of PSM parameters with pain (α = 0.05). Intraclass correlation coefficients (ICCs) for intra- and/or interreader agreement. RESULTS: The FF showed excellent intra- and interreader agreement (ICC range: 0.97-0.99) and was significantly associated with GC at all spinal levels. Subgroup analysis suggested that early/subtle changes in PSM are detectable with FF but not with GC, given the absence of significant associations between FF and GC (P-value range: 0.036 at L5/S1 to 0.784 at L2/L3). Averaged over all spinal levels, FF and GC were significantly associated with VAS scores. DATA CONCLUSION: In the absence of FF, GC may be the best surrogate for PSM quality. Given the ability of CSE-MRI to detect muscle alterations at early stages of PSM degeneration, this technique may have potential for further investigations of the role of PSM in chronic LBP. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Altered white matter structural connectivity in primary Sjögren's syndrome: a link-based analysis.

PURPOSE: Cognitive impairment has been revealed in primary Sjögren's syndrome (pSS). However, the underlying white matter structural connectivity (SC) changes have not been studied. This study aimed to investigate the altered white matter brain network in patients with pSS using diffusion tensor imaging (DTI). METHODS: Forty-one pSS patients and sixty matched healthy controls (HCs) underwent neuropsychological tests and the subsequent MRI examinations. The clinical data were gathered from the medical record. The structural brain network was established using DTI, and a link-based comparison was performed between patients with pSS and HCs (false discovery rate correction, P < 0.05). Furthermore, the mean fractional anisotropy (FA) of the altered SCs was correlated with the neuropsychological tests and clinical data in patients with pSS (Bonferroni correction, P < 0.05). RESULTS: Compared with HCs, patients with pSS mainly exhibited decreased SC in the frontal and parietal lobes and some parts of the temporal and occipital lobes. In addition, increased SC was found between the right caudate nucleus and right median cingulate/paracingulate gyri. Specifically, the reduced SC between the left middle temporal gyrus and left middle occipital gyrus was negatively correlated with white matter high signal intensity (WMH). CONCLUSIONS: Patients with pSS showed diffusely decreased SC mainly in the frontoparietal network and exhibited a negative correlation between the reduced SC and WMH. SC represents a potential biomarker for preclinical brain impairment in patients with pSS.

The Association between Allergic Rhinitis and COVID-19: A Systematic Review and Meta-Analysis.

Objective: Previous studies have yielded conflicting results regarding the association of coronavirus disease 2019 (COVID-19) with allergic rhinitis (AR). Data on AR prevalence in COVID-19 patients are limited. Consequently, whether AR is a harmful or protective factor for COVID-19 patients remains controversial. Therefore, we analyzed the relationship between COVID-19 and AR. Methods: We systematically searched PubMed, Embase, Cochrane, and Web of Science databases for studies published between January 1, 2020 and January 11, 2022. We included studies reporting the epidemiological and clinical characteristics of COVID-19 and its incidence in patients with AR. We excluded letters, case reports, literature review articles, non-English language article, and non-full-text articles. The raw data from these studies were pooled into a meta-analysis. Results: We analyzed the results of nine studies. The prevalence of AR in patients with COVID-19 was 0.13 (95% confidence interval [CI] 0.04-0.25), with an overall I 2 of 99.77%, P=0.24. COVID-19 patients with AR are less prone to severe disease (odds ratio [OR] = 0.79, 95% CI, 0.52-1.18, P=0.25) and hospitalization (OR = 0.23, 95%CI, 0.02-2.67, P ≤ 0.0001) than patients without AR. Conclusion: Our data suggest that allergic rhinitis is a protective factor in patients with COVID-19.