Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis.

Multivariate analysis of factors associated with the successful prediction of initial blind placement of a nasointestinal tube in the stomach based on X-ray imaging: a retrospective, single-center study.

BACKGROUND: Patients in the intensive care unit (ICU) are highly susceptible to malnutrition, and while enteral nutrition via nasogastric tube is the preferred method, there is a risk of inadvertent reflux and aspiration. Therefore, clinicians have turned to nasointestinal tubes (NET) for enteral nutrition as an alternative option. But the precise localization of NET presents an ongoing challenge. We proposed an innovative approach to provide a valuable reference for clinicians involved in NET placement. METHOD: Data were obtained retrospectively from the medical records of adult patients with a high risk of aspiration or gastric feeding intolerance who had a NET placed in the ICU of Zhejiang Provincial People's Hospital between October 1, 2017, and October 1, 2023. The collected data were subjected to statistical analysis using SPSS and R software. RESULT: There were 494 patients who met the inclusion and exclusion criteria. The first-pass success rate was 81.4% (n = 402). The success of a patient's initial NET placement was found to be associated with Angle SPC and Distance CP, as determined by univariate analysis (25.6 ± 16.7° vs. 41.9 ± 18.0°, P < 0.001; 40.0 ± 26.2 mm vs. 62.0 ± 31.8 mm, P < 0.001, respectively). By conducting a multivariate regression analysis, we identified a significant association between pyloric types and the success rate of placing NET (OR 29.559, 95%CI 14.084-62.038, P < 0.001). CONCLUSION: Angle SPC, Distance CP, and the type of pylorus are independently associated with successful initial placement of NET. Besides, patients with the outside type of pylorus (OP-type) exhibit a higher rate of initial placement success.

Alcohol dehydrogenase 1 is a tubular mitophagy-dependent apoptosis inhibitor against septic acute kidney injury.

Alcohol dehydrogenase 1 (ADH1) is an alcohol-oxidizing enzyme with poorlydefined biology. Here we report that ADH1 is highly expressed in kidneys of mice with lethal endotoxemia and is transcriptionally upregulated in tubular cells by lipopolysaccharide (LPS) stimuli through TLR4/NF-κB cascade. The Adh1 knockout (Adh1KO) mice with lethal endotoxemia displayed increased susceptibility to acute kidney injury (AKI) but not systemic inflammatory response. Adh1KO mice develop more severe tubular cell apoptosis in comparison to Adh1 wild-type (Adh1WT) mice during course of lethal endotoxemia. ADH1 deficiency facilitates the LPS-induced tubular cell apoptosis in a caspase-dependent manner. Mechanistically, ADH1 deficiency dampens tubular mitophagy that relies on PINK1-Parkin pathway characterized by the reduced membrane potential, reactive oxygen species (ROS) and release of fragmented mtDNA to cytosol. Kidney-specific overexpression of PINK1 and Parkin by adeno-associated viral vector 9 (AAV9) delivery ameliorates AKI exacerbation in Adh1KO mice with lethal endotoxemia. Our study supports the notion that ADH1 is critical for blockade of tubular apoptosis mediated by mitophagy, allowing the rapid identification and targeting of alcohol-metabolic route applicable to septic AKI.

Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection.

BACKGROUND: The rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China. METHODS: A total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital. RESULTS: Thirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea. CONCLUSION: The combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.

Quantifying the Contribution of the Dispersion Interaction and Hydrogen Bonding to the Anisotropic Elastic Properties of Chitin and Chitosan.

The elastic tensors of chitin and chitosan allomorphs were calculated using density functional theory (DFT) with and without the dispersion correction and compared with experimental values. The longitudinal Young's moduli were 114.9 or 126.9 GPa for α-chitin depending on the hydrogen bond pattern: 129.0 GPa for ß-chitin and 191.5 GPa for chitosan. Furthermore, the moduli were found to vary between 17.0 and 52.8 GPa in the transverse directions and between 2.2 and 15.2 GPa in shear. Switching off the dispersion correction led to a decrease in modulus by up to 63%, depending on the direction. The transverse Young's moduli of α-chitin strongly depended on the hydroxylmethyl group conformation coupled with the dispersion correction, suggesting a synergy between hydrogen bonding and dispersion interactions. The calculated longitudinal Young's moduli were, in general, higher than experimental values obtained in static conditions, and the Poisson's ratios were lower than experimental values obtained in static conditions.

Boron and nitrogen co-doped carbon nanospheres for supercapacitor electrode with excellent specific capacitance.

At present, carbon materials derived from biomass precursors have many limitations in the field of energy storage. In this study, boron and nitrogen (B/N) co-doped carbon nanospheres are successfully prepared by emulsion crosslinking method using chitosan and boric acid as raw materials. After carbonization at high temperature, the carbon nanospheres can be facilely prepared with controllable particle size, showing excellent structural stability and sphericity. In addition, the heteroatoms co-doping endows the carbon nanospheres with large specific surface area, high graphitization degree and excellent electrochemical performance. Applying the carbon nanospheres for supercapacitors, the specific capacitance can reach up to 336.7 F g-1at a current density of 1 A g-1. Even after 10,000 cycles, the Coulomb efficiency and specific capacitance still remain at 98.61% and 96.8%, respectively, demonstrating the great promise of B/N co-doped carbon nanospheres for the state-of-the-art supercapacitor electrodes applications.

Pathogen load and species monitored by droplet digital PCR in patients with bloodstream infections: A prospective case series study.

BACKGROUND AND OBJECTIVES: Bloodstream infection (BSI) is a life-threatening condition in critically ill patients, but pathogen quantification techniques during treatment are laborious. This study aimed to explore the impact of monitoring pathogen DNA load changes and polymicrobial infection in blood by droplet digital polymerase chain reaction (ddPCR) on the prognosis of patients with BSIs. METHODS: This prospective case series study was conducted in the general intensive care unit of the Zhejiang Provincial People's Hospital and included patients with BSIs from May 2020 to January 2021. Pathogens DNA load and presence of polymicrobial BSIs were dynamically monitored by ddPCR. RESULTS: Sixteen patients with BSIs proven by blood culture were recruited (87.5% men; mean age, 69.3 ± 13.7 years). All pathogens identified by blood culture were Gram-negative bacteria, among which seven were multidrug-resistant strains. The 28-day mortality rate was 62.5%. Compared to the 28-day survivors, the non-survivors were older (P = 0.04), had higher pathogen DNA load on the second (day 3-4) and third (day 6-7) ddPCR assay (P < 0.01 in both cases). In addition, the changes of pathogen DNA load in the 28-day survivors had a downward trend in the first three ddPCR assay, whereas stable load or an upward trend was observed in the 28-day non-survivors. Moreover, the number of pathogen species in patients with BSIs in the 28-day survivors decreased during the period of effective antibiotic treatment. CONCLUSION: The changes of pathogen DNA load and species monitored in blood by ddPCR may be used to determine antibiotic efficacy and make a more accurate prognostic assessment in patients with BSIs.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico-striato-thalamo-cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting-state functional connectivity (RSFC) differences of the thalamus were investigated between age-, gender-, and alcohol-matched 37 HU and 33 healthy controls (HCs). Trail making test-A (TMT-A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT-A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis.

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCFFbxw7α cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Ascorbate increases, while SVCT-1 and -2 knockout or ascorbate restriction dampens tubular mitophagy upon LPS stimuli. Treatment of endotoxemic mice with high-dose ascorbate confers mitophagy and substantial protection against mortality and septic acute kidney injury (AKI). Our work provides a rationale for clinical management of septic AKI with high doses of ascorbate.

Biomimetic-Inspired One-Step Strategy for Improvement of Interfacial Interactions in Cellulose Nanofibers by Modification of the Surface of Nitramine Explosives.

Recently, a burgeoning category of biocompatible botanically derived nanomaterial cellulose nanofibers (CNFs) has captured tremendous attention on account of its entangled nanostructured network, natural abundance, and outstanding mechanical properties. Biomimetically inspired by the superior properties of CNFs, this paper examined them as the coating material to cover cyclotrimethylenetrinitramine (RDX), cyclotetramethylenetetranitramine (HMX), and hexanitrohexaazaisowurtzitane (CL-20) via a facile water suspension method and the ultrasonic technology. The core-shell structure and the composition of energetic crystal@CNF were examined through scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy analyses. The obtained outcomes demonstrated that the dispersibility of the CNF enhanced favorably upon covering the surface of explosive crystals; the interfacial contact ability between CNFs and energetic crystals was also manifested to be increased, which could be ascribed to the interfacial interaction of hydrogen bonds and the electrostatic force of self-assembly. In addition, the stable crystalloid construction of ß-HMX and ε-CL-20 has been preserved positively in the preparation process. In comparison with raw explosives, the thermal stability and sensitivity performances of the core-shell structure composites were outstanding. Accordingly, this work demonstrated the rewarding application of coating CNFs uniformly on the surface of energetic crystals, ulteriorly offering a potential fabrication strategy for the embellishment of high-explosive crystals.

lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a.

lncRNAs play important roles in lipopolysaccharide- (LPS-) induced acute lung injury. But the mechanism still needs further research. In the present study, we investigate the functional role of the lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in LPS-induced ALI and tried to confirm its regulatory effect on autophagy. Transcriptomic profile changes were identified by RNA-seq in LPS-treated alveolar type II epithelial cells. The expression changes of lncRNA-SNHG14/miR-223-3p/Foxo3a were confirmed using qRT-PCR and west blot. The binding relationship of lncRNA-SNHG14/miR-223-3p/and miR-223-3p/Foxo3a was verified using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Using gain-of-function or loss-of-function approaches, the effect of lncRNA-SNHG14/miR-223-3p/Foxo3a was investigated in LPS-induced acute lung injury mice model and in vitro. Increasing of lncRNA-SNHG14 and Foxo3a with reducing miR-223-3p was found in LPS-treated A549 cells and lung tissue collected from the LPS-induced ALI model. lncRNA-SNHG14 inhibited miR-223-3p but promoted Foxo3a expression as a ceRNA. Artificially changes of lncRNA-SNHG14/miR-223-3p/Foxo3a pathway promoted or protected cell injury from LPS in vivo and in vitro. Autophagy activity could be influenced by lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in cells with or without LPS treatment. In conclusion, aberrant expression changes of lncRNA-SNHG14 participated alveolar type II epithelial cell injury and acute lung injury induced by LPS through regulating autophagy. One underlying mechanism is that lncRNA-SNHG14 regulated autophagy by controlling miR-223-3p/Foxo3a as a ceRNA. It suggested that lncRNA-SNHG14 may serve as a potential therapeutic target for patients with sepsis-induced ALI.

Ingenious preparation of N/NiOx co-doped hierarchical porous carbon nanosheets derived from chitosan nanofibers for high-performance supercapacitors.

It is still a key challenge to find suitable materials and methods to obtain super capacitors (SCs) with high specific capacitance due to the difficulty of balancing low theoretical capacity of conventional carbon materials and the poor ion transportability of transition metal oxide. In this work, N Ni dual-doped porous carbon nanosheets (NiOx-NCNSs) are prepared through a novel way using original N-doped chitosan nanofibers and nickel nitrate to form honeycomb layered structure constructed by 2D fiber network as precursors. NiOx-NCNS exhibits a high specific surface area of 1847.4 m2 g-1 with a rich N content of up to 5.16 wt% and shows a higher specific capacitance of 614.6 F g-1 at a current density of 1 A g-1 than that of carbon nanosheets of undoped Ni (NCNS) (427.5 F g-1). More specifically, the SC assembled using NiOx-NCNS electrodes achieves a high energy density of 20.3 W h kg-1 at a power density of 240.9 W kg-1, which is superior to most of the CNS-based SCs that have been reported. After 10 000 cycles, the symmetric SC retains approximately 85.61% of the initial capacitance. The strategy provided in this work probes the feasibility of high-performance SCs.

Inch-sized aligned polymer nanofiber films with embedded CH3NH3PbBr3 nanocrystals: electrospinning fabrication using a folded aluminum foil as the collector.

Perovskite nanocrystal embedded polymer nanofibers with polarized emissions are interesting materials for down-shifting applications. By using a folded aluminum foil as a collector, we fabricated inch-size aligned polymer nanofiber films with embedded CH3NH3PbBr3 nanocrystals by adapting an electrospinning technique. It was found that the addition of an appropriate amount of cyanoethyl cellulose (CEC) makes the dispersion of MAPbBr3 in the nanofibers more uniform. Using a precursor solution with MAPbBr3 of 10% and CEC of 1 wt%, the resulting nanofiber films show strong polarized emission with quantum yields up to 51%. The emission dichroic ratio and emission polarization ratio can reach 5.21 and 0.43, respectively. These polarized emissive films can be potentially applied as down converters for liquid crystal display backlights and other polarization selective photonic devices.

Selenoprotein T Promotes Proliferation and G1-to-S Transition in SK-N-SH Cells: Implications in Parkinson's Disease.

BACKGROUND: Selenium is prioritized to the brain mainly for selenoprotein expression. Selenoprotein T (SELENOT) protects dopaminergic, postmitotic neurons in a mouse model of Parkinson's disease (PD). OBJECTIVE: We hypothesized a proliferative role of SELENOT in neural cells. METHODS: To assess SELENOT status in PD, sedated male C57BL/6 mice at 10-12 wk of age were injected with 6-hydroxydopamine in neurons, and human peripheral blood mononuclear cells were isolated from 9 healthy subjects (56% men, 68-y-old) and 11 subjects with PD (64% men, 63-y-old). Dopaminergic neural progenitor-like SK-N-SH cells with transient SELENOT overexpression or knockdown were maintained in the presence or absence of the antioxidant N-acetyl-l-cysteine and the calcium channel blocker nimodipine. Cell cycle, proliferation, and signaling parameters were determined by immunoblotting, qPCR, and flow cytometry. RESULTS: SELENOT mRNA abundance was increased (P < 0.05) in SK-N-SH cells treated with 1-methyl-4-phenylpyridinium iodide (3.5-fold) and peripheral blood mononuclear cells from PD patients (1.6-fold). Likewise, SELENOT was expressed in tyrosine hydroxylase-positive dopaminergic neurons of 6-hydroxydopamine-injected mice. Knockdown of SELENOT in SK-N-SH cells suppressed (54%; P < 0.05) 5-ethynyl-2'-deoxyuridine incorporation but induced (17-47%; P < 0.05) annexin V-positive cells, CASPASE-3 cleavage, and G1/S cell cycle arrest. SELENOT knockdown and overexpression increased (88-120%; P < 0.05) and reduced (37-42%; P < 0.05) both forkhead box O3 and p27, but reduced (51%; P < 0.05) and increased (1.2-fold; P < 0.05) cyclin-dependent kinase 4 protein abundance, respectively. These protein changes were diminished by nimodipine or N-acetyl-l-cysteine treatment (24 h) at steady-state levels. While the N-acetyl-l-cysteine treatment did not influence the reduction in the amount of calcium (13%; P < 0.05) by SELENOT knockdown, the nimodipine treatment reversed the decreased amount of reactive oxygen species (33%; P < 0.05) by SELENOT overexpression. CONCLUSIONS: These cellular and mouse data link SELENOT to neural proliferation, expanding our understanding of selenium protection in PD.

[Clinical and genetic analysis of a patient with Perrault syndrome and additional neurological features].

OBJECTIVE: To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation. METHODS: Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing. RESULTS: The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines. CONCLUSION: Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.

Mitochondrial DNA variants modulate genetic susceptibility to Parkinson's disease in Han Chinese.

It is well recognized that mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). The mtDNA displacement loop (D-loop) region is known to accumulate structural alterations and mutations. To understand how mtDNA variants contribute to the susceptibility to sporadic PD in Chinese, a total of 500 PD patients and 505 controls were recruited from East China, and their D-loop regions were sequenced. A total of 389 variants were detected out of the 1005 subjects. There were 91 variants with frequencies >1%, which included 88 single nucleotide polymorphisms (SNPs), 2 deletions and 1 insertion. Amongst, 6 SNPs were significantly associated with sporadic PD. Specifically, the SNPs 151T/C, 189G/A, 16086C/T and 16271C/T contributed to increased susceptibility, while 318C/T and 16134T/C were associated with reduced risk for PD. Further analyses of mtDNA haplogroups and their risk for PD occurrence showed that subjects carrying haplogroup A5 were susceptible while haplogroup B5 carriers were more resistant to the disease. In summary, our study for the first time systematically analyzed mtDNA variants by sequencing the D-loop region in a Chinese population to understand their associations with PD. These results demonstrate that mtDNA variants modulate risk for sporadic PD.

A Bottom-Up Synthesis of Vinyl-Cellulose Nanosheets and Their Nanocomposite Hydrogels with Enhanced Strength.

Extracted nanocellulose from natural resources commonly requires modification before it is used as an effective nanofiller. In the present study, through an enzymatic polymerization of α-d-glucose 1-phosphate from the primer 2-(glucosyloxy)ethyl methacrylate (GEMA), a novel type of two-dimensional methacrylate-containing cellulose nanosheets (CNS) with a thickness of about 6 nm, named as GEMA-CNS, was directly synthesized under a mild condition by a "bottom-up" method. The structure and morphology of GEMA-CNS were characterized by 1H-nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectra (MALDI-TOF MS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Afterward, the obtained GEMA-CNS was covalently incorporated into poly(ethylene glycol) matrix through thiol-ene Michael addition, fabricating a series of GEMA-CNS-based nanocomposite hydrogels. The addition of GEMA-CNS effectively improved the mechanical strength and altered the internal network structures of hydrogels; additionally, the swelling/biodegradation behaviors of gels in phosphate buffer saline (pH 7.4) at 37 °C were affected to some degree. This species of property-tunable hydrogels with GEMA-CNS dosage demonstrates potential applications in tissue engineering. The current presentation opens a new road for direct enzymatic preparation of reactive nanocellulose and its novel applications in nanocomposite materials.

Development and validation of a nomogram for predicting the placement of nasointestinal tubes in critically ill patients based on abdominal radiography: A single-center, retrospective study.

Background: Enteral nutrition administered via the nasointestinal tube (NET) is a prevalent nutritional modality among critically ill patients, and abdominal radiographs hold significant value in accurately ascertaining the precise positioning of the NET subsequent to its placement. Therefore, we propose an innovative approach to construct a clinical prediction model based on NET's configuration within the gastrointestinal tract in abdominal radiography. This model aims to enhance the accuracy of determining the position of NETs after their placement. Methods: Patients admitted to the intensive care unit of Zhejiang Provincial People's Hospital between October 2017 and October 2021 were included to constitute the training cohort for retrospective analysis, and nomogram was constructed. Consecutively enrolled patients admitted to the same hospital from October 2021 to October 2023 were included as the validation cohort. The training cohort underwent a univariate analysis initially, followed by a multivariate logistic regression approach to analyze and identify the most appropriate model. Subsequently, nomogram was generated along with receiver operator characteristic curves, calibration curves, and decision curves for both the training and validation cohorts to evaluate the predictive performance of the model. Results: The training and validation cohorts comprised 574 and 249 patients, respectively, with successful tube placement observed in 60.1 % and 76.3 % of patients, correspondingly. The predictors incorporated in the prediction maps encompass the "C-shape," the height of "inverse C-shape," showing the duodenojejunal flexure, and the location of the head end of the NET. The model demonstrated excellent predictive efficacy, achieving an AUC of 0.883 (95 % CI 0.855-0.911) and good calibration. Furthermore, when applied to the validation cohort, the nomogram exhibited strong discrimination with an AUC of 0.815 (95 % CI 0.750-0.880) and good calibration. Conclusion: The combination of abdominal radiography and NET's configuration within the gastrointestinal tract enables accurate determination of NET placement in critically ill patients.