Ropivacaine combined with dexmedetomidine in ultrasound-guided axillary brachial plexus block in children, a randomized controlled trial.

OBJECTIVE: In this study, we evaluated the efficacy and safety of 1 µg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia. METHODS: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 µg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications. RESULTS: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05). CONCLUSION: Dexmedetomidine (1 µg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery. CLINICAL REGISTRY NUMBER: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.

High efficiency of biosurfactants in stabilizing oil micro-droplets within the aging time scale of milliseconds: a microfluidic study.

Rapid adsorption of surfactants onto a freshly formed interface is vital for emulsification because emulsification is a competitive process occurring between the very short time span of interface formation and surfactant mass transport. The biosurfactant surfactin has been previously reported to reach adsorption equilibrium at the hydrophobic/hydrophilic interface within hundreds of milliseconds and rapidly reduce the interfacial tension compared to chemically synthesized surfactants. According to a prior study, surfactin is expected to exhibit good performance in stabilizing micro-droplets of oil within the aging time scale of milliseconds. Herein, the stabilities of micro-droplets of n-hexadecane in the presence of a biosurfactant, surfactin (C15-SFT), and a chemically synthesized surfactant, sodium cetyl benzene sulfonate (8-SCBS), were investigated using a microfluidic method. The coalescence frequency of micro-droplets, the evolution of micro-droplet size, and the coalescence time of micro-droplets were evaluated. The results indicated that C15-SFT exhibited superiority over 8-SCBS in stabilizing the micro-droplets of n-hexadecane. Biosurfactant C15-SFT effectively reduced the fusion probability between oil droplets and elongated the coalescence time compared to 8-SCBS, and these phenomena were obvious at a shorter aging time (150 ms) and lower surfactant concentration (0.1 × critical micelle concentration). The stabilities of micro-droplets increased with aging time and the bulk concentration of surfactants. Stable micro-droplets of n-hexadecane were formed in 1 × 10-4 mol L-1 C15-SFT solution at 600 ms aging time, and the bulk concentration was 1 × 10-3 mol L-1 in the case of 8-SCBS. The micro-droplets rarely coalesced in the presence of 1 × 10-4 mol L-1 C15-SFT after 600 ms aging time, but the micro-droplets in 1 × 10-4 mol L-1 8-SCBS coalesced frequently in the midstream and downstream of the coalescence chamber, and big droplets were dominant in the emulsion. The coalescence time of micro-droplets stabilized by C15-SFT was obviously longer than that of those stabilized by 8-SCBS under the same condition, indicating that the interfacial film formed by C15-SFT has much strength to resist coalescence during collisions. This work is helpful for understanding the activity of lipopeptides in the very short early stage of the emulsification process, laying the foundation for biosurfactant research in the fields of enhanced oil recovery, bioremediation of contaminated water or soil, etc.

Hippocampal adenosine-to-inosine RNA editing in sepsis: dynamic changes and influencing factors.

Sepsis-associated encephalopathy is a diffuse brain dysfunction secondary to infection. It has been established that factors such as age and sex can significantly contribute to the development of sepsis-associated encephalopathy. Our recent study implicated a possible link between adenosine-to-inosine RNA editing and sepsis-associated encephalopathy, yet the dynamics of adenosine-to-inosine RNA editing during sepsis-associated encephalopathy and how it could be influenced by factors such as age, sex and antidepressants remain uninvestigated. Our current study analysed and validated transcriptome-wide changes in adenosine-to-inosine RNA editing in the hippocampus of different septic mouse models. Seventy-four sites in 64 genes showed significant differential RNA editing over time in septic mice induced by caecal ligation and perforation. The differential RNA editing might contribute to the RNA expression regulation of the edited genes, with 42.2% differentially expressed. These differentially edited genes, especially those with missense editing, such as glutamate receptor, ionotropic, kainate 2 (Grik2, p.M620V), filamin A (Flna, p.S2331G) and capicua transcriptional repressor (Cic, p.E2270G), were mainly involved in abnormal social behaviour and neurodevelopmental and psychiatric disorders. Significant effects of age and sex were also observed on sepsis-associated RNA editing. Further comparison highlighted 40 common differential RNA editing sites that caecal ligation and perforation-induced and lipopolysaccharide-induced septic mouse models shared. Interestingly, these findings demonstrate temporal dynamics of adenosine-to-inosine RNA editing in the mouse hippocampus during sepsis, add to the understanding of age and sex differences in the disease and underscore the role of the epigenetic process in sepsis-associated encephalopathy.

Conversion and fate of waste Li-ion battery electrolyte in a two-stage thermal treatment process.

Disposal of electrolytes from waste lithium-ion batteries (LIBs) has gained much more attention with the growing application of LIBs, yet handling spent electrolyte is challengeable due to its high toxicity and the lack of established methods. In this study, a novel two-stage thermal process was developed for treating residual electrolytes resulted from spent lithium-ion batteries. The conversion of fluorophosphate and organic matter in oily electrolyte during low-temperature rotation distillation was investigated. The distribution and migration of the concentrated electrolytes were studied and the corresponding reaction mechanisms were elucidated. Additionally, the influence of alkali on the fixation of fluorine and phosphate was further examined. The results indicated that hydrolyzed carbonate esters and lithium in the electrolyte could combine to form Li2CO3 and the hydrolysable hexafluorophosphate was proven to be stable in the concentrated electrolyte (45 rpm/85 °C, 30 min). It was found that CO2, CO, CH4, and H2 were the primary pyrolysis gases, while the pyrolysis oil consisted of extremely flammable substances formed by the dissociation and recombination of chemical bonds in the electrolyte solvent. After pyrolysis at 300 °C, fluorine and phosphate were present in the form of sodium fluoride and sodium phosphate. The stability of the residue was enhanced, and the environmental risk was reduced. By adding alkali (KOH/Ca(OH)2, 20 %), hexafluorophosphate in the electrolyte was transformed into fluoride and phosphate in the residue, thereby reducing the device's corrosion from fluorine-containing gas. This study provides a viable approach for managing the residual electrolyte in the waste lithium battery recovery process.

Novel Systemic Inflammatory Markers Predict All-Cause Mortality in Patients Undergoing Endovascular Abdominal Aortic Aneurysm Repair.

Background: Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. Methods: A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan-Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. Results: The study included 147 patients, with an average follow-up duration of 34.28 ± 22.95 months. Deceased patients showed significantly higher NLR (p < 0.001) and reduced HRR (p < 0.001). The Kaplan-Meier estimates of mortality were considerably greater in the higher-NLR group (NLR > 2.77) and lower-HRR group (HRR < 10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71-0.97, p < 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Conclusions: Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.

Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

[Research progress in targeting DNA G-quadruplexes using natural products].

DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.

Pyrrolopyrrole Cyanine J-Aggregate Nanoparticles with High Near-Infrared Fluorescence Brightness and Photothermal Performance for Efficient Phototheranostics.

Advanced photosensitizers for high-performance fluorescence imaging-guided photothermal therapy demand excellent near-infrared (NIR) brightness [molar absorption coefficient (ε) × quantum yield (QY)] and exceptional photothermal performance [ε × photothermal conversion efficiency (PCE)]. However, integrating high brightness and potent photothermal performance within a single molecule faces a formidable challenge. This article proposes a method to address this issue by preparing J-aggregate nanoparticles (NPs) using molecules with high ε. J-aggregates effectively improve QY and induce molecular emission redshift, while high ε molecules play a crucial role in improving the brightness and photothermal performance. By optimizing the molecular structure based on the pyrrolopyrrole cyanine (PPCy), precise control over the QY and PCE of PPCy J-aggregates is achieved. Ultimately, PDDO NPs exhibiting superior brightness (ε × QY = 3.32 × 104 M-1 cm-1) and photothermal performance (ε × PCE = 1.21 × 105 M-1 cm-1) are identified as high-performance photosensitizers. Notably, each parameter represents one of the highest levels among the reported fluorescence or photothermal probes to date. The in vivo studies demonstrate that PDDO NPs possess exceptional NIR imaging capabilities and remarkable photothermal tumor inhibition rates. This study provides innovative insights into the development of high-performance multifunctional photosensitizers.

Aerial signaling by plant-associated Streptomyces setonii WY228 regulates plant growth and enhances salt stress tolerance.

Plant-associated streptomycetes play important roles in plant growth and development. However, knowledge of volatile-mediated crosstalk between Streptomyces spp. and plants remains limited. In this study, we investigated the impact of volatiles from nine endophytic Streptomyces strains on the growth and development of plants. One versatile strain, Streptomyces setonii WY228, was found to significantly promote the growth of Arabidopsis thaliana and tomato seedlings, confer salt tolerance, and induce early flowering and increased fruit yield following volatile treatment. Analysis of plant growth-promoting traits revealed that S. setonii WY228 could produce indole-3-acetic acid, siderophores, ACC deaminase, fix nitrogen, and solubilize inorganic phosphate. These capabilities were further confirmed through genome sequencing and analysis. Volatilome analysis indicated that the volatile organic compounds emitted from ISP-2 medium predominantly comprised sesquiterpenes and 2-ethyl-5-methylpyrazine. Further investigations showed that 2-ethyl-5-methylpyrazine and sesquiterpenoid volatiles were the primary regulators promoting growth, as confirmed by experiments using the terpene synthesis inhibitor phosphomycin, pure compounds, and comparisons of volatile components. Transcriptome analysis, combined with mutant and inhibitor studies, demonstrated that WY228 volatiles promoted root growth by activating Arabidopsis auxin signaling and polar transport, and enhanced root hair development through ethylene signaling activation. Additionally, it was confirmed that volatiles can stimulate plant abscisic acid signaling and activate the MYB75 transcription factor, thereby promoting anthocyanin synthesis and enhancing plant salt stress tolerance. Our findings suggest that aerial signaling-mediated plant growth promotion and abiotic stress tolerance represent potentially overlooked mechanisms of Streptomyces-plant interactions. This study also provides an exciting strategy for the regulation of plant growth and the improvement of horticultural crop yields within sustainable agricultural practices.

Successively Controlling Nanoscale Wrinkles of Ultrathin 2D Metal-Organic Framework Nanosheets.

The wrinkles are pervasive in ultrathin two-dimensional (2D) materials, but the regulation of wrinkles is rarely explored systematically. However, the regulation of wrinkles at nanometer scale is merely explored. Here, we employed a series of carboxylic acids (from formic acid to octanoic acid) to control the wrinkles of Zr-BTB (BTB = 1, 3, 5-(4-carboxylphenyl)-benzene) metal-organic framework (MOF) nanosheet. The wrinkles at the micrometer scale were observed with transmission electron microscopy. Furthermore, high-angle annular dark-field (HAADF) images showed lattice distortion in many nanoscale regions, which was precisely matched to the nano-wrinkles. With the changes of hydrophilicity/hydrophobicity, MOF-MOF and MOF-solvent interactions were synergistically regulated and wrinkles with different sizes were obtained, which was supported by HAADF, molecular dynamics and density functional theory calculation. Different wrinkle sizes resulted in different pore sizes between the Zr-BTB nanosheet interlayers, providing highly-oriented thin films and the successive optimization of kinetic diffusion pathways, proved by grazing-incidence wide-angle X-ray scattering and nitrogen adsorption. The most suitable wrinkle pore from Zr-BTB-C4 exhibited highly efficient chromatographic separation of the substituted benzene isomers. Our work provides a rational route for the modulation of nanoscale wrinkles and their stacked pores of MOF nanosheets and improves the separation abilities of MOFs.

Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota.

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Modeling multi-component separation in hydrophobic interaction chromatography with improved parameter-by-parameter estimation method.

Mechanistic models are powerful tools for chromatographic process development and optimization. However, hydrophobic interaction chromatography (HIC) mechanistic models lack an effective and logical parameter estimation method, especially for multi-component system. In this study, a parameter-by-parameter method for multi-component system (called as mPbP-HIC) was derived based on the retention mechanism to estimate the six parameters of the Mollerup isotherm for HIC. The linear parameters (ks,i and keq,i) and nonlinear parameters (ni and qmax,i) of the isotherm can be estimated by the linear regression (LR) and the linear approximation (LA) steps, respectively. The remaining two parameters (kp,i and kkin,i) are obtained by the inverse method (IM). The proposed method was verified with a two-component model system. The results showed that the model could accurately predict the protein elution at a loading of 10 g/L. However, the elution curve fitting was unsatisfactory for high loadings (12 g/L and 14 g/L), which is mainly attributed to the demanding experimental conditions of the LA step and the potential large estimation error of the parameter qmax. Therefore, the inverse method was introduced to further calibrate the parameter qmax, thereby reducing the estimation error and improving the curve fitting. Moreover, the simplified linear approximation (SLA) was proposed by reasonable assumption, which provides the initial guess of qmax without solving any complex matrix and avoids the problem of matrix unsolvable. In the improved mPbP-HIC method, qmax would be initialized by the SLA and finally determined by the inverse method, and this strategy was named as SLA+IM. The experimental validation showed that the improved mPbP-HIC method has a better curve fitting, and the use of SLA+IM reduces the error accumulation effect. In process optimization, the parameters estimated by the improved mPbP-HIC method provided the model with excellent predictive ability and reasonable extrapolation. In conclusion, the SLA+IM strategy makes the improved mPbP-HIC method more rational and can be easily applied to the practical separation of protein mixture, which would accelerate the process development for HIC in downstream of biopharmaceuticals.

PuERF008-PuFAD2 module regulates aroma formation via the fatty acid pathway in response to calcium signaling in 'Nanguo' pear.

Calcium acts as a secondary messenger in plants and is essential for plant growth and development. However, studies on the pathway of aroma synthesis in 'Nanguo' pear (Pyrus ussriensis Maxim.) are scarce. In this study, a bioinformatics analysis of transcriptomic data from calcium-treated 'Nanguo' pear was performed, which identified two fatty acid desaturases, PuFAD2 and PuFAD3, and eight AP2/ERF transcription factors, all exhibiting the same expression patterns. Transient expression experiments showed overexpression of PuFAD2 and PuFAD3 significantly increased the levels of aromatic substrates linoleic acid, hexanal, linolenic acid, and (E)-2-hexenal, but RNAi (RNA interference) had the opposite expression. Promoter sequences analysis revealed that PuFAD2 and PuFAD3 have ERE (estrogen response element) motifs on their promoters. The strongest activation of PuFAD2 by PuERF008 was verified using a dual-luciferase reporting system. Additionally, yeast one-hybrid and electrophoretic mobility shift assays revealed PuERF008 could active PuFAD2. Transient overexpression and RNAi analyses of PuERF008 showed a strong correlation with the expression of PuFAD2. This study provides insights into the process of aroma biosynthesis in 'Nanguo' pear and offers a theoretical basis for elucidating the role of calcium signaling in aroma synthesis.

First-principles calculation of structural, electronic, optical, and mechanical properties of SrVO3.

CONTEXT AND RESULTS : In this paper, the crystal structure, electronic, optical, and mechanical properties of SrVO3 have been systematically studied by first-principles calculation. The results show that the calculated lattice parameters are in good agreement with the experimental values of X-ray diffraction. The density of states is described in detail in this paper. By analyzing the crystal structure and electronic properties of SrVO3, the magnetic properties of SrVO3 are obtained from the one unpaired electrons of V and the exchange interaction between two V ions. At the same time, a detailed analysis of the optical properties of SrVO3 was conducted, and it was found that it is transparent in the visible light range. Finally, the mechanical properties of SrVO3 are calculated, which can provide some references for future research. COMPUTATIONAL METHOD: In this paper, a first-principles method based on density functional theory (DFT) is reported for PBE-GGA analysis using the plane wave-pseudo potential method in a quantum concentrate packet, U value of 7 eV to V-d and a U value of 2 eV to O-p, Grimme correction by DFT-D method. The k points in the Brillouin region are set to 4 × 4 × 4. The energy convergence criterion for self-consistent field calculation is set at 5.0 × 10-6 eV/atom, and the cutoff energy is 1170 eV. In this paper, the force acting on each atom is not more than 0.01 eV/Å, the maximum stress is not more than 0.02GPa, and the maximum atomic displacement is 5 × 10-4 Å.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

A smooth vetch (Vicia villosa var.) strain endogenous to the broad-spectrum antagonist Bacillus siamensis JSZ06 alleviates banana wilt disease.

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4), poses a significant threat to banana production globally, thereby necessitating effective biocontrol methods to manage this devastating disease. This study investigates the potential of Bacillus siamensis strain JSZ06, isolated from smooth vetch, as a biocontrol agent against Foc TR4. To this end, we conducted a series of in vitro and in vivo experiments to evaluate the antifungal activity of strain JSZ06 and its crude extracts. Additionally, genomic analyses were performed to identify antibiotic synthesis genes, while metabolomic profiling was conducted to characterize bioactive compounds. The results demonstrated that strain JSZ06 exhibited strong inhibitory activity against Foc TR4, significantly reducing mycelial growth and spore germination. Moreover, scanning and transmission electron microscopy revealed substantial ultrastructural damage to Foc TR4 mycelia treated with JSZ06 extracts. Genomic analysis identified several antibiotic synthesis genes, and metabolomic profiling revealed numerous antifungal metabolites. Furthermore, in pot trials, the application of JSZ06 fermentation broth significantly enhanced banana plant growth and reduced disease severity, achieving biocontrol efficiencies of 76.71% and 79.25% for leaves and pseudostems, respectively. In conclusion, Bacillus siamensis JSZ06 is a promising biocontrol agent against Fusarium wilt in bananas, with its dual action of direct antifungal activity and plant growth promotion underscoring its potential for integrated disease management strategies.

Unraveling the intricacies of glycosaminoglycan biosynthesis: Decoding the molecular symphony in understanding complex polysaccharide assembly.

Glycosaminoglycans (GAGs) are extensively utilized in clinical, cosmetic, and healthcare field, as well as in the treatment of thrombosis, osteoarthritis, rheumatism, and cancer. The biological production of GAGs is a strategy that has garnered significant attention due to its numerous advantages over traditional preparation methods. In this review, we embark on a journey to decode the intricate molecular symphony that orchestrates the biosynthesis of glycosaminoglycans. By unraveling the complex interplay of related enzymes and thorough excavation of the intricate metabolic cascades involved, GAGs chain aggregation and transportation, which efficiently and controllably modulate GAGs sulfation patterns involved in biosynthetic pathway, we endeavor to offer a thorough comprehension of how these remarkable GAGs are intricately assembled and pushes the boundaries of our understanding in GAGs biosynthesis.

Development and validation of a nomogram for predicting lymph node metastasis in early gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) significantly impacts the treatment and prognosis of early gastric cancer (EGC). Consequently, the precise prediction of LNM risk in EGC patients is essential to guide the selection of appropriate surgical approaches in clinical settings. AIM: To develop a novel nomogram risk model for predicting LNM in EGC patients, utilizing preoperative clinicopathological data. METHODS: Univariate and multivariate logistic regression analyses were performed to examine the correlation between clinicopathological factors and LNM in EGC patients. Additionally, univariate Kaplan-Meier and multivariate Cox regression analyses were used to assess the influence of clinical factors on EGC prognosis. A predictive model in the form of a nomogram was developed, and its discrimination ability and calibration were also assessed. RESULTS: The incidence of LNM in the study cohort was 19.6%. Multivariate logistic regression identified tumor size, location, degree of differentiation, and pathological type as independent risk factors for LNM in EGC patients. Both tumor pathological type and LNM independently affected the prognosis of EGC. The model's performance was reflected by an area under the curve of 0.750 [95% confidence interval (CI): 0.701-0.789] for the training group and 0.763 (95%CI: 0.687-0.838) for the validation group. CONCLUSION: A clinical prediction model was constructed (using tumor size, low differentiation, location in the middle-lower region, and signet ring cell carcinoma), with its score being a significant prognosis indicator.