Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer.

Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.

A new FRET-based fluorescent probe: Colorimetric and ratiometric detection of hypochlorite and anti-counterfeiting applications.

Hypochlorite (ClO-), as the main component of widely used disinfectants in daily life, comes into closer contact with the human body, which can lead to a number of diseases. The high-performance method is increasingly needed to detect ClO- in our daily life. In this report, we successfully synthesized a FRET ratiometric fluorescent probe (NDAC) containing benzoxadiazole moieties and coumarin moieties bound via ethylenediamine. As expected, NDAC has excellent selectivity and anti-interference ability toward ClO-, and the ratio of fluorescence intensity (I471 nm/I533 nm) has a very good linear relationship with the concentration of ClO-, with a wide linear range (2.5-1750 µM) and low detection limit (0.887 µM). Furthermore, we have successfully applied it for the quantitative detection of ClO- in water samples in daily life. At the same time, there is a very clear change in the fluorescence color after the reaction of the NDAC with ClO-. The blue/green value (B/G) of this color change also shows a very good linear relationship to ClO- (5.0-1000 µM). Therefore, the NDAC has also been successfully used for test strip detection and quantitative detection of ClO- in actual samples through smartphone-based fluorescence image analysis, and this method can provide faster, more convenient and more accessible detection. In addition, NDAC sensors also have potential applications in the field of information anti-counterfeiting.

Post-translational regulation of muscle growth, muscle aging and sarcopenia.

Skeletal muscle makes up 30-40% of the total body mass. It is of great significance in maintaining digestion, inhaling and exhaling, sustaining body posture, exercising, protecting joints and many other aspects. Moreover, muscle is also an important metabolic organ that helps to maintain the balance of sugar and fat. Defective skeletal muscle function not only limits the daily activities of the elderly but also increases the risk of disability, hospitalization and death, placing a huge burden on society and the healthcare system. Sarcopenia is a progressive decline in muscle mass, muscle strength and muscle function with age caused by environmental and genetic factors, such as the abnormal regulation of protein post-translational modifications (PTMs). To date, many studies have shown that numerous PTMs, such as phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, glycation, methylation, S-nitrosylation, carbonylation and S-glutathionylation, are involved in the regulation of muscle health and diseases. This article systematically summarizes the post-translational regulation of muscle growth and muscle atrophy and helps to understand the pathophysiology of muscle aging and develop effective strategies for diagnosing, preventing and treating sarcopenia.

Novel Aggregation-Induced Emission Fluorescent Molecule for Platinum(IV) Ion-Selective Recognition and Imaging of Controlled Release in Cells.

The loading, delivery, and release of Pt(IV) precursors in living organisms are important aspects of exploring the development of platinum drugs. In recent years, the biological application of the fluorescent sensors to platinum drugs has been insufficient to meet the study of Pt(IV) precursors. It is urgent to design and develop a biocompatible, multifunctional fluorescent sensor for the study of loading, transport, and release of Pt(IV) ions. Herein, we report a fluorescent molecule (E)-6-(diethylamino)-N'-(4-(diphenylamino) benzylidene)-2-oxo-2H-chromene-3 carbohydrazide (CHTPA). CHTPA has good sensitivity and selectivity to Pt(IV) when the water content is 5%, and significant increase of the fluorescence emission intensity of CHTPA is observed with Pt(IV) concentration. The sensing mechanism is attributed to photo-induced electron transfer, which is verified by X-ray absorption near edge spectroscopy spectra, UV-vis absorption spectroscopy, 1H NMR spectra, and Fourier transform infrared spectra. Furthermore, the CHTPA-Pt(IV) complex is able to release Pt(IV) in aqueous solution, and the green fluorescence of CHTPA based on the aggregation-induced emission effect can be observed. Inspired by these, the amphiphilic block copolymer poly(ethyloxide)-block-polystyrene (PEO-b-PS) is used to prepare the nonconjugated polymer dots (Pdots). The experimental results show that Pdots can effectively slow down the release speed of Pt(IV) in aqueous solution and it has a great monodispersity in aqueous solution. Meanwhile, Pdots show low cytotoxicity, and this is favorable for intracellular applications. The investigation of cellular imaging indicates that these Pdots can act as a carrier to deliver Pt(IV) into MCF-7 cells for visualized delivery and sustained release of platinum(IV) ions. Therefore, this study provides a new avenue to design and develop a biocompatible multifunctional fluorescent sensor for studying the loading, delivery, and release of Pt(IV) in cells.

M1 Microglia Induced Neuronal Injury on Ischemic Stroke via Mitochondrial Crosstalk between Microglia and Neurons.

Among the middle-aged and senile populations, ischemic stroke (IS) is a frequently occurring acute condition of the cerebrovascular system. Traditionally, it is recognized that when stroke occurs, microglia are activated into M1 phenotype and release cytotoxic cytokines, reactive oxygen species, proteases, and other factors, thus exacerbating the injury by further destroying or killing nearby neurons. In the latest research, the crucial role of the intercellular mitochondrial crosstalk on the stroke management has been demonstrated. Therefore, we tried to clarify mitochondrial crosstalk between microglia and neurons, and evaluated M1 microglial mitochondria-mediated neurological performance in transient middle cerebral artery occlusion (tMCAO) rats. We found that when microglia was activated into the proinflammatory M1 type after stroke, mitochondrial fission process was accelerated, and damaged mitochondria were released, further transferred to neurons and fused with neuronal mitochondria. As a result, the function of neuronal mitochondria was damaged by decreasing adenosine triphosphate (ATP), mitochondria membrane potential, and increasing excessive reactive oxygen species (ROS), thus inducing mitochondria-mediated neuronal death and finally aggravating ischemia injury. Taken together, it provides a novel neuroglial crosstalk mechanism at the mitochondrial level.

Plasma metabolomics and lipidomics signatures of motoric cognitive risk syndrome in community-dwelling older adults.

Introduction: Motoric cognitive risk syndrome (MCR) is characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Metabolomics and lipidomics may potentiate disclosure of the underlying mechanisms of MCR. Methods: This was a cross-sectional study from the West China Health and Aging Trend cohort study (WCHAT). The operational definition of MCR is the presence of SCCs and SG without dementia or mobility disability. The test and analysis were based on untargeted metabolomics and lipidomics, consensus clustering, lasso regression and 10-fold cross-validation. Results: This study enrolled 6,031 individuals for clinical analysis and 577 plasma samples for omics analysis. The overall prevalence of MCR was 9.7%, and the prevalence of MCR-only, assessed cognitive impairment-only (CI-only) and MCR-CI were 7.5, 13.3, and 2.1%, respectively. By consensus clustering analysis, MCR-only was clustered into three metabolic subtypes, MCR-I, MCR-II and MCR-III. Clinically, body fat mass (OR = 0.89, CI = 0.82-0.96) was negatively correlated with MCR-I, and comorbidity (OR = 2.19, CI = 1.10-4.38) was positively correlated with MCR-III. Diabetes mellitus had the highest ORs above 1 in MCR-II and MCR-III (OR = 3.18, CI = 1.02-9.91; OR = 2.83, CI = 1.33-6.04, respectively). The risk metabolites of MCR-III showed relatively high similarity with those of cognitive impairment. Notably, L-proline, L-cystine, ADMA, and N1-acetylspermidine were significantly changed in MCR-only, and PC(40:3), SM(32:1), TG(51:3), eicosanoic acid(20:1), methyl-D-galactoside and TG(50:3) contributed most to the prediction model for MCR-III. Interpretation: Pre-dementia syndrome of MCR has distinct metabolic subtypes, and SCCs and SG may cause different metabolic changes to develop MCR.

Combination of 3.0T magnetic resonance imaging T2 mapping with texture analysis for evaluating the degeneration of lumbar facet joints. / 3.0Tç£å ±æŒ¯æˆåƒT2 mappingè”åˆçº¹ç†åˆ†æžè¯„ä¼°è °æ¤Žå°å ³èŠ‚é€€å˜ç¨‹åº¦.

OBJECTIVES: Quantitative magnetic resonance imaging has been successfully applied to assess the status of cartilage biochemical components. This study aimed to investigate the performance of 3.0T magnetic resonance imaging T2 mapping combined with texture analysis for evaluating the early degeneration of lumbar facet joints. METHODS: A total of 38 patients (20 in the asymptomatic group and 18 in the symptomatic group) were enrolled. All patients underwent 3.0T magnetic resonance imaging conventional sequences, water excitation three-dimensional spoiled gradient echo sequence (3D-WATSc), and T2 mapping scans. The bilateral L4/5 and L5/S1 lumbar facet joints were morphological graded using the Weishaupt criteria, T2 values, and texture parameters derived from T2 mapping of cartilage. The Kruskal-Wallis H test was used to compare the differences of parameters among different groups. Multivariate logistic regression analysis was used to obtain the independent predictive factors for evaluating the early degeneration of lumbar facet joints. Receiver operating characteristic (ROC) curve was performed and the area under curve (AUC) was calculated. Spearman correlation analysis was used to evaluate the correlation of the independent predictors of cartilage T2 value and texture parameters with the subjects' Japanese Orthopedic Association (JOA) score or Visual Analogue Scale (VAS) score. RESULTS: A total of 148 facet joints were selected, including 70 in Weishaupt 0 (normal) group, 58 in Weishaupt 1 group, and 20 in Weishaupt 2-3 group. T2 value, entropy, and contrast increased significantly as the exacerbation of facet joint degeneration (all P<0.05), while the inverse difference moment, energy, and correlation decreased (all P<0.05). Entropy among different groups was significantly different (all P<0.05), and the differences of T2 value, contrast, inverse difference moment, and energy between Weishaupt 0 and Weishaupt 1 groups, or Weishaupt 0 and Weishaupt 2-3 groups were statistically significant (all P<0.05). Multivariate logistic regression analysis suggested that T2 value and inverse difference moment were the independent predictors for evaluating early degeneration of facet joints. The combination of T2 value with inverse difference moment achieved the best performance in distinguishing Weishaupt 0 from Weishaupt 1 (AUC=0.85), with sensitivity and specificity at 92.7% and 76.5%, respectively. In the symptom group, the cartilage T2 value combined inverse difference moment was positively correlated with JOA score (r=0.475, P<0.05) and VAS score (r=0.452, P<0.05). CONCLUSIONS: 3.0T magnetic resonance imaging T2 mapping combined with texture analysis is helpful to quantitatively evaluate the early degeneration of lumbar facet joints, in which the T2 value and inverse difference moment show an indicative significance．.

Epidemiological survey of ticks and tick-borne pathogens in pet dogs in south-eastern China.

To understand the epidemiology of tick infestation and tick-borne diseases in pet dogs in south-eastern China and to develop a reference for their prevention and treatment, we collected 1550 ticks parasitizing 562 dogs in 122 veterinary clinics from 20 cities of south-eastern China. Dogs were tested for common tick-borne pathogens; collected ticks were identified and processed for the detection of tick-borne pathogens. The use of an in vitro ELISA diagnostic kit for antibody detection (SNAP®4Dx® Plus) on dog sera found the infection rates with Borrelia burgdorferi sensu lato, Ehrlichia canis, and Anaplasma spp. to be 0.4%, 1.3% and 2.7%, respectively. By using a specific ELISA method, the infection rate with Babesia gibsoni was 3.9%. Rhipicephalus sanguineus sensu lato, Haemaphysalis longicornis and Rhipicephalus haemaphysaloides were the major tick species identified on pet dogs. PCR tests were conducted to detect five tick-borne pathogens in 617 ticks. The infection rate was 10.2% for E. canis, 3.4% for Anaplasma platys, 2.3% for B. gibsoni, 0.3% for B. burgdorferi s.l. and 0% for Babesia canis. Some ticks were co-infected with two (1.46%) or three pathogens (0.16%). These results indicate the infestation of pet dogs by ticks infected with tick-borne pathogens in south-eastern China, and the need for effective treatment and routine prevention of tick infestations in dogs.

Clinical diagnosis and mutation analysis of a Chinese family with Camurati-Engelmann disease.

Camurati-Engelmann disease (CED) is a rare autosomal dominant bone disorder caused by a mutation in transforming growth factor ß1 (TGFß1). The present study aimed to identify a Chinese family with suspected CED based on the clinical symptoms, including pain in extremities, waddling gait, muscle weakness, cortical thickening of the diaphysis of the long bones, and sclerosis of the skull, facial bone, and pelvis. Molecular analysis revealed the presence of the p.Glu169Lys (E169K) mutation in exon 2 of TGFß1 in patients when compared with the controls. Therefore, the Chinese family was diagnosed with CED due to the presence of the E169K mutation. The present study emphasized the importance of clinical and genetic evidence for the diagnosis of CED. The data presented in the present study are of significance to clinicians, as well as genetic counselors, in the prenatal screening of CED.

A new marker, SOX11, aids the diagnosis of mantle cell lymphoma in the prostate: A case report.

Mantle cell lymphoma (MCL) of the prostate, either primary or secondary, is a rare entity. This case report examines an 83-year-old male who complained of not only nocturia (2-3 times), but also frequency and urgency of urination. The maximal urinary flow rate was 4.1 ml/sec. A transrectal ultrasound-guided prostate biopsy was advised after a hard enlargement of the prostate was detected; however, it was refused. Therefore, a plasma kinetic transurethral resection of the prostate was performed. Postoperative pathological examinations demonstrated MCL of the prostate. Positive immunohistochemistry for CD5 and cyclin D1 was observed. The diagnosis was confirmed by the introduction of a new diagnostic marker, SOX11. The maximal flow rate achieved was 15 ml/sec following surgery. To the best of our knowledge, this is the first study of MCL being diagnosed using SOX11 as a marker in the prostate. This case should alert clinicians and pathologists to pay close attention to the diagnosis of malignant lymphoma of the prostate. This study provides further insights into the diagnosis and therapy of MCL.

Clinical features and pedigree report of a patient with giant neurofibroma.

Neurofibromatosis (NF) is a genetically inherited, autosomal-dominant disease with an incidence of 1/3,000 in live births. There are two types of NF, NF 1 and NF 2, and NF 1 is the most common type. This study reports on the diagnosis, treatment, and related family medical history of a rare case with NF-1 in the right lower leg.

First reported fatal Morganella morganii infections in chickens.

Morganella morganii, a Gram-negative rod commonly found in the intestines of humans and other animals, is here confirmed to cause a fatal infection in chickens by isolation and identification of the bacteria, 16S rRNA gene sequencing, and experimental infection. This is the first case of M. morganii infection in chickens.

Clinical images. Extragastrointestinal stromal tumor of lesser omentum mimicking a liver tumor.

Extragastrointestinal stromal tumors are rare, so clinicopathologic features are not fully elucidated. We report a large extragastrointestinal stromal tumor of the lesser omentum mimicking a liver tumor.