Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

Spheroid models to elaborate the broken symmetry and equivalent volume of molecules in crystalline phase.

Dense packing of particles has provided powerful models to elaborate the important structural features of matter in various systems such as liquid, glassy, and crystalline phases. The simplest sphere packing models can represent and capture salient properties of the building blocks for covalent, metallic, and ionic crystals; it, however, becomes insufficient to reflect the broken symmetry of the commonly anisotropic molecules in molecular crystals. Here, we develop spheroid models with a minimal degree of anisotropy, which serve as a simple geometrical representation for a rich spectrum of molecules-including both isotropic and anisotropic, convex and concave ones-in crystalline phases. Our models are determined via an inverse packing approach: Given a molecular crystal, an optimal spheroid model is constructed using a contact diagram, which depicts the packing relationship between neighboring molecules within the crystal. The spheroid models are capable of accurately capturing the broken symmetry and characterizing the equivalent volume of molecules in the crystalline phases. Moreover, our model retrieves such molecular information from low-quality x-ray diffraction data with poorly resolved structures, and by using soft spheroids, it can also describe the packing behavior in cocrystals.

Risk Factors and Predictive Nomogram for Survival in Elderly Patients with Brain Glioma.

OBJECTIVE: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram. METHODS: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA). RESULTS: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance. CONCLUSION: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making.

Mesoporous Vinylene-Linked Covalent Organic Frameworks with Heteroatom-Tuned Crystallinity and Photocatalytic Behaviors.

Owing to its prominent π-delocalization and stability, vinylene linkage holds great merits in the construction of covalent organic frameworks (COFs) with promising semiconducting properties. However, carbon-carbon double bond formation reaction always exhibits relatively low reversibility, unfavorable for the formation of high crystalline frameworks through self-error correction and assembling processes. In this work, we report a heteroatom-tuned strategy to build up a series of two-dimensional (2D) vinylene-linked COFs by Knoevenagel condensation of an electron-deficient methylthiazolyl-based monomer with different triformyl substituted (hetero-)aromatic derivatives. The resulting COFs show high-quality periodic mesoporous structures with high surface areas. Embedding heteroatoms into the backbones enables significantly improving their crystallinity, and finely tailoring their semiconducting structures. Upon visible light stimulation, one of the as-prepared COFs with donor-π-acceptor structure could deliver a nearly seven-fold increase in the catalytic activity of hydrogen generation as compared with the other two. Meanwhile, in combination with high crystallinity and the matched conduction band energy level, such kind of COFs can be able to selectively generate singlet oxygen and superoxide radicals in a high ratio of up to 30:1, allowing for catalyzing aerobic thioanisole oxidation in distinctly tunable activities through the substituent electronic effect of the substrates.

The role of quercetin in ameliorating bleomycin-induced pulmonary fibrosis: insights into autophagy and the SIRT1/AMPK signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. CONCLUSION: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion.

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Real-world safety and effectiveness of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. METHODS: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. RESULTS: A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. CONCLUSION: The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.

Colorimetric-SERS dual-mode aptasensor for Staphylococcus aureus based on MnO2@AuNPs oxidase-like activity.

The nanozyme-linked aptamer-sorbent assay (NLASA) is a rapid way to screen and characterize aptamer binding to targets. In this paper, a MnO2@AuNPs@aptamer (Apt) based NLASA coupled with colorimetric-SERS dual-mode for Staphylococcus aureus (S. aureus) detection is presented. Cu,Fe-CDs were used as the reducing agent to synthesize MnO2 and gold nanoparticles (AuNPs). Then, they were fabricated to obtain MnO2@AuNPs with oxidase (OXD)-like and SERS activities. The S. aureus aptamer was conjugated to MnO2@AuNPs and enhanced the OXD-like activity, which realized the specific capture of S. aureus in food matrices. In addition, S. aureus improves the oxidation of 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid (ABTS) but inhibits 3,3',5,5'-tetramethylbenzidine (TMB) to generate Raman-active oxTMB with MnO2@AuNPs@Apt. This sensor was used for detections of S. aureus in a concentration ranged from 101 to 107 CFU/mL with a detection limit of 0.926 CFU/mL (colorimetric) and 1.561 CFU/mL (SERS), and the recovery is 85%-105% in real samples.

Pyridazine-Promoted Construction of Vinylene-Linked Covalent Organic Frameworks with Exceptional Capability of Stepwise Water Harvesting.

In this study, we successfully developed two novel vinylene-linked covalent organic frameworks (COFs) using 2-connected 3,6-dimethylpyridazine through Knoevenagel condensation. These COFs featured finely tailored micro-/nano-scale pore sizes, high surface areas and stable non-polar vinylene linkages. Finely resolved powder X-ray diffraction patterns demonstrated highly crystalline structures with a hexagonal lattice in the AA layer stacking. The resulting one-dimensional channels possess strong hydrogen-bond accepting sites arising from the decorated cis-azo/azine units with two pairs of fully exposed lone pair electrons, endowing the as-prepared COFs with exceptional water absorption properties. The g-DZPH-COF exhibited successive steep water uptake steps starting from low relative pressures (P/PSTA=0.1), with the remarkable water uptake capacity of 0.26 g/g at P/PSTA=0.2 (25 °C), which is the optimal value recorded among the reported COFs. Dynamic vapour sorption measurements revealed the fast kinetics of these COFs, even in the cluster formation process. Water uptake and release cycling tests demonstrated their outstanding hydrolytic stability, durability, and adsorption-desorption retention ability.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

Characterization of a methyltransferase for iterative N-methylation at the leucinostatin termini in Purpureocillium lilacinum.

N-methyltransferase (NMT)-catalyzed methylation at the termini of nonribosomal peptides (NRPs) has rarely been reported. Here, we discover a fungal NMT LcsG for the iterative terminal N-methylation of a family of NRPs, leucinostatins. Gene deletion results suggest that LcsG is essential for leucinostatins methylation. Results from in vitro assays and HRESI-MS-MS analysis reveal the methylation sites as NH2, NHCH3 and N(CH3)2 in the C-terminus of various leucinostatins. LcsG catalysis yields new lipopeptides, some of which demonstrate effective antibiotic properties against the human pathogen Cryptococcus neoformans and the plant pathogen Phytophthora infestans. Multiple sequence alignments and site-directed mutagenesis of LcsG indicate the presence of a highly conserved SAM-binding pocket, along with two possible active site residues (D368 and D395). Molecular dynamics simulations show that the targeted N can dock between these two residues. Thus, this study suggests a method for increasing the variety of natural bioactivity of NPRs and a possible catalytic mechanism underlying the N-methylation of NRPs.

Identification and validation of a novel risk model based on cuproptosis­associated m6A for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA). METHODS: RNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC. RESULTS: A risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups. CONCLUSIONS: Our risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.

Safety of Traditional Growing Rods in Patients with Early-Onset Congenital Scoliosis Associated with Type-I Split Cord Malformation.

BACKGROUND: Literature regarding the application of traditional growing rod (TGR) instrumentation in patients with early-onset congenital scoliosis with type-I split cord malformation is scarce. The purpose of the present study was to assess the safety and effectiveness of TGR surgery and repeated lengthening procedures in patients with congenital scoliosis with type-I split cord malformation not treated with prophylactic osseous spur excision. METHODS: Thirteen patients with early-onset congenital scoliosis associated with type-I split cord malformation and a stable neurologic status between March 2009 and July 2020 were recruited. All patients underwent primary TGR surgery and subsequent repeated lengthening procedures without osseous spur excision by the same surgical team. Clinical information and radiographic data from the preoperative, postoperative, and latest follow-up periods were collected. RESULTS: The mean preoperative Cobb angle of the major coronal curve was 74.62° ± 25.59°, the mean early postoperative angle was 40.23° ± 17.89°, and the mean latest follow-up angle was 40.62° ± 16.60°. The scoliotic deformity correction percentage was 46.81% ± 12.26% after the initial operation and 45.08% ± 15.53% at the latest follow-up. Compared with the preoperative values, significant improvements were observed in the coronal and sagittal balance early postoperatively and at the latest follow-up (p < 0.05 for all). The average annual amounts of spinal height gained were 15.73 ± 5.95 mm at T1-S1, 8.94 ± 3.94 mm at T1-T12, and 12.02 ± 6.70 mm between the instrumented segments. The total height gained at T1-S1 and T1-T12 was 72.18 ± 28.74 mm and 37.62 ± 12.53 mm, respectively. No intraoperative neurophysiological monitoring events were observed, and no case of neurological deficit was observed postoperatively or during follow-up. CONCLUSIONS: Patients without neurologic deficit and having a stable neurologic exam who have early-onset congenital scoliosis associated with type-I split cord malformation can safely and effectively undergo TGR surgery, followed by repeated lengthening procedures, without prophylactic osseous spur excision. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently.

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

Precise Helium Sieving from Hydrogen Using Fluorine-Decorated Carbon Hollow Fiber Membranes.

Separating helium (He) and hydrogen (H2), two gases that are extremely similar in molecular size and condensation properties, presents a formidable challenge in the helium industry. The development of membranes capable of precisely differentiating between these gases is crucial for achieving large-scale, energy-efficient He/H2 separation. However, the limited selectivity of current membranes has hindered their practical application. In this study, we propose a novel approach to overcome this challenge by engineering submicroporous membranes through the fluorination of partially carbonized hollow fibers. We demonstrate that the fluorine substitution on the inner rim of the micropore walls within the carbon hollow fibers enables tunability of the microporous architecture. Furthermore, it enhances interactions between H2 molecules and the micropore walls through the polarization and hydrogen bonding induced by C-F bonds, resulting in simultaneous improvements in both He/H2 diffusivity and solubility selectivities. The fluorinated HFM-550-F-1 min membrane exhibits exceptional mixed-gas separation performance, with a binary mixed-gas He/H2 selectivity of 10.5 and a ternary mixed-gas He/(H2+CO2) selectivity of 20.8, at 40 bar feed pressure and 35 °C, surpassing all previously reported polymer-based gas separation membranes, and remarkable plasticization resistance and long-term continuous stability over 30 days.

The Metabolic Functional Feature of Gut Microbiota in Mongolian Patients with Type 2 Diabetes.

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. ß-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

Aptamer-functionalized Fe3O4/MWCNTs@Mo-CDs nanozyme for rapid colorimetric detection toward Escherichia coli.

The pathogenic bacteria induced foodborne disease has been detrimental to public health worldwide. Herein, the peroxidase (POD)-like Fe3O4/MWCNTs@Mo-CDs (FMMC) nanozyme was applied for the detection of Escherichia coli (E. coli). The E. coli aptamer was conjugated with the surface of the FMMC, which effectively enhanced the POD-like activity attributing to the higher affinity to the substrate, and then specific capture of E. coli in food matrices, leading to the reduction of POD-like activity. Therefore, a robust and facile colorimetric aptasensor was developed for detecting E. coli with a wide linear range of 101-106 CFU/mL, low LOQ of 101 CFU/mL and LOD of 0.978 CFU/mL. The aptasensor demonstrated the satisfied selectivity for E. coli compared to the other strains. This method possessed the potential application for fast in situ screening of foodborne pathogens in food products.

New insights into the roles of olfactory receptors in cardiovascular disease.

Olfactory receptors (ORs) are G protein coupled receptors (GPCRs) with seven transmembrane domains that bind to specific exogenous chemical ligands and transduce intracellular signals. They constitute the largest gene family in the human genome. They are expressed in the epithelial cells of the olfactory organs and in the non-olfactory tissues such as the liver, kidney, heart, lung, pancreas, intestines, muscle, testis, placenta, cerebral cortex, and skin. They play important roles in the normal physiological and pathophysiological mechanisms. Recent evidence has highlighted a close association between ORs and several metabolic diseases. Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. Furthermore, ORs play an essential role in the development and functional regulation of the cardiovascular system and are implicated in the pathophysiological mechanisms of CVDs, including atherosclerosis (AS), heart failure (HF), aneurysms, and hypertension (HTN). This review describes the specific mechanistic roles of ORs in the CVDs, and highlights the future clinical application prospects of ORs in the diagnosis, treatment, and prevention of the CVDs.