Random forest differentiation of Escherichia coli in elderly sepsis using biomarkers and infectious sites.

This study addresses the challenge of accurately diagnosing sepsis subtypes in elderly patients, particularly distinguishing between Escherichia coli (E. coli) and non-E. coli infections. Utilizing machine learning, we conducted a retrospective analysis of 119 elderly sepsis patients, employing a random forest model to evaluate clinical biomarkers and infection sites. The model demonstrated high diagnostic accuracy, with an overall accuracy of 87.5%, and impressive precision and recall rates of 93.3% and 87.5%, respectively. It identified infection sites, platelet distribution width, reduced platelet count, and procalcitonin levels as key predictors. The model achieved an F1 Score of 90.3% and an area under the receiver operating characteristic curve of 88.0%, effectively differentiating between sepsis subtypes. Similarly, logistic regression and least absolute shrinkage and selection operator analysis underscored the significance of infectious sites. This methodology shows promise for enhancing elderly sepsis diagnosis and contributing to the advancement of precision medicine in the field of infectious diseases.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Construction and results of a comprehensive index for gastrointestinal health monitoring in China: a nationwide study.

Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Sphingopyxis yananensis sp. nov., a novel 2-nitropropane degrading bacterium isolated from a microbial fermentation bed substrate.

A rod-shaped, Gram-negative staining strain, FBM22T, was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 µm wide, 0.5-0.83 µm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C18:1 ω7c, C16:1 ω7c and/ or C16:1 ω6c, and C14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098T (96.40%). Furthermore, FBM22T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2T and S. terrae subsp. terrae NBRC 15098T). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22T (= KCTC 82290T = CCTC AB2020286T).

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

[Insight into the role of IGF2BP1 in drug resistant mechanism of oral squamous cell carcinoma].

PURPOSE: This study focused on the role and mechanism of IGF2BP1 in cell cisplatin resistance of oral squamous cell carcinoma. METHODS: Low-dose intermittent induction method was used to induce cisplatin-sensitive oral squamous cell carcinoma cell line HN30, and establish cisplatin-resistant cell line HN30/DDP. Western blot was used to detect the protein expression level of IGF2BP1 in parental and resistant cell line. Knockdown or overexpression of IGF2BP1 by RNAi and lentivirus transfection method was utilized to analyze the effect of decreased or increased the gene expression of IGF2BP1 on cisplatin resistance. MTT method was used to detect the change of IC50. Statistical analysis of data was performed using SPSS 17.0 software package. RESULTS: Cisplatin-resistant oral squamous cell carcinoma cell line was successfully established. The IC50 of the drug-resistant cells was significantly higher than that of the parental cells. Knocking down the expression level of IGF2BP1 in drug-resistant strains reduced cell resistance; on the contrary, after overexpression of IGF2BP1 in parental cells dramatically increased cisplatin resistance. Mechanically, activation of Akt signaling pathway was the key factor mediating IGF2BP1 to promote cisplatin resistance in oral squamous cell carcinoma. CONCLUSIONS: IGF2BP1 is significantly associated with cisplatin resistance in oral squamous cell carcinoma. IGF2BP1 can promote cisplatin resistance of oral squamous cells by activating downstream Akt signaling pathway.

Tracking the interaction of drug molecules with individual mesoporous amorphous calcium phosphate/ATP nanocomposites - an X-ray spectromicroscopy study.

Adenosine triphosphate (ATP) biomolecules play critial roles in the biomineralization process during the formation of amorphous calcium phosphate composites (ACPC), and ACPC is an important drug carrier due to its significant advantages of biocompatibility and biodegradability. Hence, studying the behavior of ACPC nanodrug carriers is crucial to investigate the structural regulation of biomimetic minerals and calcium phosphate (CaP)-based drug delivery systems. However, it is difficult to probe these interactions using traditional characterization methods. In this paper, XANES analysis together with STXM successfully provided a method to reveal the interaction of ATP and drug molecules with individual mesoporous ACPC. We found that the adenosine and phosphate groups of ATP biomolecules coordinated with Ca2+ and played critical roles in the formation of ACPC; drug molecules with the -COOH groups were linked to Ca2+via carboxylic acid groups primarily by electrostatic interactions, and the N-containing ring structures within the drug molecules also coordinated with Ca2+.

Selenium-doped hydroxyapatite biopapers with an anti-bone tumor effect by inducing apoptosis.

One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.

Enzymatic Reaction Generates Biomimic Nanominerals with Superior Bioactivity.

In vivo mineralization is a multistep process involving mineral-protein complexes and various metastable compounds in vertebrates. In this complex process, the minerals produced in the mitochondrial matrix play a critical role in initiating extracellular mineralization. However, the functional mechanisms of the mitochondrial minerals are still a mystery. Herein, an in vitro enzymatic reaction strategy is reported for the generation of biomimic amorphous calcium phosphate (EACP) nanominerals by an alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) in a weakly alkalescent aqueous condition (pH 8.0-8.5), which is partially similar to the mitochondrial environment. Significantly, the EACP nanomineral obviously promotes autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway, and displays a high performance in promoting bone regeneration. These results provide in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process, demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases.

Porous Nanocomposite Comprising Ultralong Hydroxyapatite Nanowires Decorated with Zinc-Containing Nanoparticles and Chitosan: Synthesis and Application in Bone Defect Repair.

Hydroxyapatite nanowires exhibit a great potential in biomedical applications owing to their high specific surface area, high flexibility, excellent mechanical properties, and similarity to mineralized collagen fibrils of natural bone. In this work, zinc-containing nanoparticle-decorated ultralong hydroxyapatite nanowires (Zn-UHANWs) with a hierarchical nanostructure have been synthesized by a one-step solvothermal method. The highly flexible Zn-UHANWs exhibit a hierarchical rough surface and enhanced specific surface area as compared with ultralong hydroxyapatite nanowires (UHANWs). To evaluate the potential application of Zn-UHANWs in bone regeneration, the biomimetic Zn-UHANWs/chitosan (CS) (Zn-UHANWs/CS) composite porous scaffold with 80 wt % Zn-UHANWs was prepared by incorporating Zn-UHANWs into the chitosan matrix by the freeze-drying process. The as-prepared Zn-UHANWs/CS composite porous scaffold exhibits enhanced mechanical properties, highly porous structure, and excellent water retention capacity. In addition, the Zn-UHANWs/CS porous scaffold has a good biodegradability with the sustainable release of Zn, Ca, and P elements in aqueous solution. More importantly, the Zn-UHANWs/CS porous scaffold can promote the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells and facilitate in vivo bone regeneration as compared with the pure CS porous scaffold or UHANWs/CS porous scaffold. Thus, both the Zn-UHANWs and Zn-UHANWs/CS porous scaffold developed in this work are promising for application in bone defect repair.

Antibacterial gluey silver-calcium phosphate composites for dentine remineralization.

The development of multifunctional dental-restorative biomaterials with antibacterial activity and remineralization effect for damaged tooth repair is urgent since dental caries is still one of the most common tooth diseases in human beings. Herein, we report a facile strategy for the synthesis of gluey silver-calcium phosphate (GSCP) composites using the rapid microwave-assisted solvothermal method. The as-prepared GSCP composite is an organic-inorganic hybrid, and Ag+ ions display a significant influence on the formation of GSCP by interacting with adenosine triphosphate biomolecules. The as-prepared GSCP composite shows good antibacterial properties, in addition, it exhibits a great effect on sheltering dentinal canaliculi and improving the remineralization of dentine in the simulated saliva. The as-prepared GSCP composite is promising for various applications such as oral healthcare, especially, remineralization of dentine, and antibacterial applications.

Current treatment status and barriers for patients with chronic HCV infection in mainland China: A national multicenter cross-sectional survey in 56 hospitals.

Chronic hepatitis C virus (HCV) infection is a serious public health problem worldwide. China, as the country with the largest number of HCV infections in the world, plays a significant role in eliminating hepatitis C. Due to different financial situations and education background, hepatitis C patients take different actions for their disease treatment and management. Therefore, antiviral treatment status should be attached great importance to learn the medical demand of patients. A nationwide, multicenter survey was conducted from July 2015 to June 2016. Of 1798 inpatients and outpatients with chronic HCV from 56 hospitals participated in the survey. Each patient completed the questionnaire with questions about his/her antiviral therapy status, perception of treatment barriers, and expectations for future treatment. In total 1622 patients, including 1241 with chronic hepatitis C, 344 with cirrhosis, and 37 patients with hepatocellular carcinoma, fulfilled data collection requirements and finally were included in analysis. Overall, up to 30.7% of the patients had not or currently does not intend to receive antiviral therapy. The main reason was expecting more potent and well-tolerance medication (31.5%), followed by the fear of interferon related side effects (27.5%). Multiple regression analysis showed that the patient's annual income, the severity of HCV, and comorbidity were independent predictors of not receiving antiviral therapy. The whole patients were expecting more potent and well tolerance medication available soon. In summary, Peg-IFN/RBV treatment regimen cannot meet the need of patients well, and safe and efficient direct-acting antivirals are urgently needed in mainland China.

Templated solvothermal synthesis of magnesium silicate hollow nanospheres with ultrahigh specific surface area and their application in high-performance protein adsorption and drug delivery.

Magnesium silicate nanostructured biomaterials with good biocompatibility and high adsorption capacity for drugs and proteins are promising for applications in various biomedical fields. However, the applications of magnesium silicate nanostructured biomaterials in anticancer drug delivery and protein adsorption have rarely been reported so far. Herein, we report a facile strategy for the synthesis of magnesium silicate hollow nanospheres (MSHNSs) by a classical Stöber method and a template based solvothermal process. The as-prepared MSHNSs have an ultrahigh specific surface area of 585.6 m2 g-1, ultrahigh hemoglobin (Hb) protein adsorption capacity (1262 mg g-1) and high doxorubicin (DOX) drug loading capacity (559 mg g-1). Moreover, the as-prepared MSHNS/DOX drug delivery system exhibits sustained and pH-responsive drug release performance. Compared with free DOX, the MSHNS/DOX drug delivery system exhibits higher anticancer activity in vitro, and thus it is promising for applications in anticancer treatment.

Electrospinning of PELA/PPY Fibrous Conduits: Promoting Peripheral Nerve Regeneration in Rats by Self-Originated Electrical Stimulation.

Peripheral nerve injuries represent a great challenge for surgeons. The conductive neural scaffold has experienced increasing interest because of its good biocompatibility and similar electrical properties as compared to those of a normal nerve. Herein, nerve conduits made from poly(d,l-lactide)-co-poly(ethylene glycol) and polypyrrole (20%, 30%, and 50%) (PELA-PPY) were prepared by electrospinning, and used in regeneration of peripheral nerve defects. The results of an in vitro experiment indicated a high biocompatibility for the as-prepared materials, supporting the attachment and proliferation of a rat pheochromocytoma PC-12 cell. Furthermore, the PELA-PPY nerve conduit implanted in the sciatic nerve defects (10 mm) of the Spraguee-Dawley rats for 12 weeks showed similar results with the autograft, while it demonstrated a better outcome than the PELA nerve conduit in electrophysiological examination, sciatic function index, total amount of regenerated myelinated nerve fibers, axon diameter, myelin thickness, and several immunohistochemistry indices (S-100, laminin, neurofilament, bromodeoxyuridine, and glial fibrillary acidic portein). We supposed that the bioactivity is mainly generated by the PPY in composite nanofibers which could transmit self-originated electrical stimulation between cells. Due to the facile preparation and excellent in vivo performance, the PPY-PELA nerve conduit is promising for use as a bioengineered biomaterial for peripheral nerve regeneration.

Vesicle-like nanospheres of amorphous calcium phosphate: sonochemical synthesis using the adenosine 5'-triphosphate disodium salt and their application in pH-responsive drug delivery.

A rapid and simple strategy is reported for the synthesis of amorphous calcium phosphate (ACP) vesicle-like nanospheres using the adenosine 5'-triphosphate (ATP) disodium salt as a biocompatible phosphorus source and stabilizer by the sonochemical method in mixed solvents of water and ethylene glycol (EG). The ACP vesicle-like nanospheres are characterized by X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV/Vis absorption spectroscopy, thermogravimetric (TG) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), dynamic light scattering (DLS) and Brunauer-Emmett-Teller (BET) nitrogen adsorption. The ACP vesicle-like nanospheres exhibit essentially inappreciable toxicity to the cells in vitro. Furthermore, the as-prepared ACP vesicle-like nanospheres can be used as anticancer drug nanocarriers and show a pH-responsive drug release behaviour using doxorubicin (Dox) as a model drug. The ACP vesicle-like nanosphere drug delivery system exhibits a high ability to damage cancer cells, thus, it is promising for application in pH-responsive drug delivery.

NQO1 609C>T polymorphism interaction with tobacco smoking and alcohol drinking increases colorectal cancer risk in a Chinese population.

BACKGROUND: NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case-control study to evaluate the potential association between NQO1 609C>T polymorphisms and colorectal cancer risk in a Chinese population. METHODS: The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations. RESULTS: The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR=2.02, 95% CI=1.55-2.57; TT: adjusted OR=2.51, 95% CI=1.82-3.47), compared with the CC genotype. Moreover, NQO1 609C>T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk. CONCLUSION: Our findings suggest that the NQO1 609C>T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.

Structural phylogenomics uncovers the early and concurrent origins of cysteine biosynthesis and iron-sulfur proteins.

Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ~3.5 billion years ago while the tRNA-independent counterpart emerged ~500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.

SO2 gas separation using supported ionic liquid membranes.

Measurements of permeability of sulfur dioxide (SO2) in five imidazolium-based ionic liquids supported on the polyethersulfone microfiltration membranes at temperatures from 25 to 45 degrees C and atmospheric pressure indicate that under the same conditions, the SO2 selectivity of separations using supported ionic liquid membranes are 9-19 times that of CO2.