Stabilizing Interlayer Repulsion in Layered Sodium-Ion Oxide Cathodes via Hierarchical Layer Modification.

Layered sodium-ion oxides hold considerable promise in achieving high-performance sodium-ion batteries. However, the notorious phase transformation during charging, attributed to increased O2-─O2- repulsion, results in substantial performance decay. Here, a hierarchical layer modification strategy is proposed to stabilize interlayer repulsion. During desodiation, migrated Li+ from the transition metal layer and anchored Ca2+ in sodium sites maintain the cationic content within the sodium layer. Meanwhile, partial oxygen substitution by fluorine and the involvement of oxygen in redox reactions increase the average valence of the oxygen layer. This sustained cation presence and elevated anion valence collectively mitigate increasing O2-─O2- repulsion during sodium extraction, enabling the Na0.61Ca0.05[Li0.1Ni0.23Mn0.67]O1.95F0.05 (NCLNMOF) cathode to retain a pure P2-type structure across a wide voltage range. Unexpected insights reveal the interplay between different doping elements: the robust Li─F bonds and Ca2+ steric effects suppressing Li+ loss. The NCLNMOF electrode exhibits 82.5% capacity retention after 1000 cycles and a high-rate capability of 94 mAh g-1 at 1600 mA g-1, demonstrating the efficacy of hierarchical layer modification for high-performance layered oxide cathodes.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Exploring the feasibility of remote administration of speech audiometry: A comparative study of conventional and digital methods.

Objective: This study investigated the effectiveness of remote administration of speech audiometry, an essential tool for diagnosing hearing loss and determining its severity. Utilizing two software tools for remote testing, the research aimed to compare these digital methods with traditional, in-person speech audiometry to evaluate their feasibility and accuracy. Design: Participants underwent the Cantonese Hearing in Noise Test (CHINT) under three listening conditions-quiet, noise from the front, and noise from the right side-using three different administration methods: the conventional in-person approach, video conferencing software, and remote access software. Study Sample: Fifty-six Cantonese-speaking adults residing in Hong Kong participated in this study. Results: Analysis revealed no significant differences in CHINT scores among the three administration methods, indicating the potential for remote administration to yield results comparable to those of conventional methods. Conclusions: The findings supported the feasibility of remote speech audiometry using the investigated digital tools. This study paved the way for the wider adoption of tele-audiology practices, particularly in situations where in-person assessments are not possible.

PARP inhibitor boost the efficacy of photothermal therapy to TNBC through enhanced DNA damage and inhibited homologous recombination repair.

Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.

Exploring the nematicidal mechanisms and control efficiencies of oxalic acid producing Aspergillus tubingensis WF01 against root-knot nematodes.

Background and aims: Root-knot nematodes (RKN; Meloidogyne spp.) are among the highly prevalent and significantly detrimental pathogens that cause severe economic and yield losses in crops. Currently, control of RKN primarily relies on the application of chemical nematicides but it has environmental and public health concerns, which open new doors for alternative methods in the form of biological control. Methods: In this study, we investigated the nematicidal and attractive activities of an endophytic strain WF01 against Meloidogyne incognita in concentration-dependent experiments. The active nematicidal metabolite was extracted in the WF01 crude extract through the Sephadex column, and its structure was identified by nuclear magnetic resonance and mass spectrometry data. Results: The strain WF01 was identified as Aspergillus tubingensis based on morphological and molecular characteristics. The nematicidal and attractive metabolite of A. tubingensis WF01 was identified as oxalic acid (OA), which showed solid nematicidal activity against M. incognita, having LC50 of 27.48 µg ml-1. The Nsy-1 of AWC and Odr-7 of AWA were the primary neuron genes for Caenorhabditis elegans to detect OA. Under greenhouse, WF01 broth and 200 µg ml-1 OA could effectively suppress the disease caused by M. incognita on tomatoes respectively with control efficiency (CE) of 62.5% and 70.83%, and promote plant growth. In the field, WF01-WP and 8% OA-WP formulations showed moderate CEs of 51.25%-61.47% against RKN in tomato and tobacco. The combined application of WF01 and OA resulted in excellent CEs of 66.83% and 69.34% toward RKN in tomato and tobacco, respectively. Furthermore, the application of WF01 broth or OA significantly suppressed the infection of J2s in tomatoes by upregulating the expression levels of the genes (PAL, C4H, HCT, and F5H) related to lignin synthesis, and strengthened root lignification. Conclusion: Altogether, our results demonstrated that A. tubingensis WF01 exhibited multiple weapons to control RKN mediated by producing OA to lure and kill RKN in a concentration-dependent manner and strengthen root lignification. This fungus could serve as an environmental bio-nematicide for managing the diseases caused by RKN.

Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer.

BACKGROUND: The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM: To identify serum protein biomarkers for the early screening of AA and CRC. METHODS: We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS: A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION: Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.

Screening and Anti-angiogenesis Activity of Chiloscyllium plagiosum Anti-human VEGFR2 Single-domain Antibody.

Recently, the incidence of malignant tumors is on the rise and searching for new treatments on it has become the research priority. Blocking the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is one of the treatment strategies that used in the development of specific anti-angiogenic drugs. The deficiencies in tissue penetration and affinity maturation become the weakness of these drugs in anti-tumors applications. The single heavy chain antibody found in Chiloscyllium plagiosum, which has a low molecular weight and superior tissue penetration of variable region (VNARs), was considered to have the high antigen binding activity and stability. This type of antibody has a simple structure that can be prokaryoticaly expressed, which makes it easily to produce new antiangiogenic target drugs. Specific anti-IgNAR rabbit multiple antibodies have been used to assess the level of VNARs in sharks and have shown a significant enrichment of IgNAR after triple immunization. An anti-VEGFR2 phage library was used for the targeted VNARs screening, and five candidate VNARs sequences were subsequently obtained by phage screening, followed by combined screening with the transcriptome library, and analysis of conserved regions along with 3D modelling matched the VNAR profile. ELISA and cell-based assays showed that two of the VNARs, VNAR-A6 and VNAR-E3, had a superior antigen affinity and anti-angiogenic activity thereby being able to inhibit human Umbilical Vein Endothelial Cells proliferation and migration. The anti-VEGFR2 VNARs derived from the immunized Chiloscyllium plagiosum and screened by phage library, which provide the new research ideas and specific approaches for the development of new drugs. The anti-VEGFR2 VNARs are capable for blocking the VEGF-VEGFR pathway, which of these may contribute to expanding the use of anti-angiogenic drugs.

Modulation of sleep/wake patterns by gephyrin phosphorylation status.

Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho-proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on-demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, α1- and α2-GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of α1-GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake-dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV-eGFP-gephyrin or its phospho-null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep.

Candidatus Liberibacter asiaticus influences the emergence of the Asian citrus psyllid Diaphorina citri by regulating key cuticular proteins.

The Asian citrus psyllid, Diaphorina citri, is the primary vector of the HLB pathogen, Candidatus Liberibacter asiaticus (CLas). The acquisition of CLas shortens the developmental period of nymphs, accelerating the emergence into adulthood and thereby facilitating the spread of CLas. Cuticular proteins (CPs) are involved in insect emergence. In this study, we investigated the molecular mechanisms underlying CLas-promoted emergence in D. citri via CP mediation. Here, a total of 159 CP genes were first identified in the D. citri genome. Chromosomal location analysis revealed an uneven distribution of these CP genes across the 13 D. citri chromosomes. Proteomic analysis identified 54 differentially expressed CPs during D. citri emergence, with 14 CPs exhibiting significant differential expression after CLas acquisition. Five key genes, Dc18aa-1, Dc18aa-2, DcCPR-24, DcCPR-38 and DcCPR-58, were screened from the proteome and CLas acquisition. The silencing of these 5 genes through a modified feeding method significantly reduced the emergence rate and caused various abnormal phenotypes, indicating the crucial role that these genes play in D. citri emergence. This study provides a comprehensive overview of the role of CPs in D. citri and reveals that CLas can influence the emergence process of D. citri by regulating the expression of CPs. These key CPs may serve as potential targets for future research on controlling huanglongbing (HLB) transmission.

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization.

Palladium-catalyzed enantioselective C(sp3)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective ß-C(sp3)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp3)-H functionalization reactions.

Functional Analysis of the Major Pilin Proteins of Type IV Pili in Streptococcus sanguinis CGMH010.

The pil gene cluster for Type IV pilus (Tfp) biosynthesis is commonly present and highly conserved in Streptococcus sanguinis. Nevertheless, Tfp-mediated twitching motility is less common among strains, and the factors determining twitching activity are not fully understood. Here, we analyzed the functions of three major pilin proteins (PilA1, PilA2, and PilA3) in the assembly and activity of Tfp in motile S. sanguinis CGMH010. Using various recombinant pilA deletion strains, we found that Tfp composed of different PilA proteins varied morphologically and functionally. Among the three PilA proteins, PilA1 was most critical in the assembly of twitching-active Tfp, and recombinant strains expressing motility generated more structured biofilms under constant shearing forces compared to the non-motile recombinant strains. Although PilA1 and PilA3 shared 94% identity, PilA3 could not compensate for the loss of PilA1, suggesting that the nature of PilA proteins plays an essential role in twitching activity. The single deletion of individual pilA genes had little effect on the invasion of host endothelia by S. sanguinis CGMH010. In contrast, the deletion of all three pilA genes or pilT, encoding the retraction ATPase, abolished Tfp-mediated invasion. Tfp- and PilT-dependent invasion were also detected in the non-motile S. sanguinis SK36, and thus, the retraction of Tfp, but not active twitching, was found to be essential for invasion.

Risk factors and clinical prediction models for prolonged mechanical ventilation after heart valve surgery.

OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.

Effect of salinity on the physiological response and transcriptome of spotted seabass (Lateolabrax maculatus).

Salinity fluctuations significantly impact the reproduction, growth, development, as well as physiological and metabolic activities of fish. To explore the osmoregulation mechanism of aquatic organisms acclimating to salinity stress, the physiological and transcriptomic characteristics of spotted seabass (Lateolabrax maculatus) in response to varying salinity gradients were investigated. In this study, different salinity stress exerted inhibitory effects on lipase activity, while the impact on amylase activity was not statistically significant. Notably, a moderate increase in salinity (24 psu) demonstrated the potential to enhance the efficient utilization of proteins by spotted seabass. Both Na+/K+-ATPase and malondialdehyde showed a fluctuating trend of increasing and then decreasing, peaking at 72 h. Transcriptomic analysis revealed that most differentially expressed genes were involved in energy metabolism, signal transduction, the immune response, and osmoregulation. These results will provide insights into the molecular mechanisms of salinity adaptation and contribute to sustainable development of the global aquaculture industry.

Efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (rTMS) for migraine: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation in the prevention or treatment of migraine by conducting a pooled analysis of relevant randomized controlled trials. METHODS: The PubMed, Embase, Cochrane, OVID, SCOPUS, Web of Science, and clinicaltrials.gov databases were systematically searched for randomized controlled trials (RCTs) comparing high-frequency rTMS and sham stimulation for the prevention or treatment of migraine. A meta-analysis of relevant outcome measures was performed using RevMan 5.3 software. RESULTS: Eight RCTs with a total of 384 patients were included. A total of 23 patients dropped out, and thus, 361 patients were ultimately included for analysis. The high-frequency rTMS group had a lower frequency of attacks than the sham group (MD = - 5.10; 95% CI: - 8.10, - 2.09; P = 0.0009). The rTMS group has less intense headaches than the sham group (SMD = - 0.74; 95% CI - 1.04, - 0.44; P < 0.00001). High-frequency rTMS improved patient disability (SMD = - 0.45; 95% CI - 0.75, - 0.16; P = 0.003). High-frequency rTMS led to no advantage in reducing the number of abortive medications (MD = - 1.10; 95% CI - 3.28, 1.08; P = 0.32), but it increased the occurrence of adverse events (RR = 1.69; 95% CI 1.09, 2.64; P = 0.02). CONCLUSIONS: High-frequency rTMS reduces the frequency of attacks and headache intensity in migraine patients and improves the patient's disability, but it also increases adverse events.

Comparison of B cells' immune response induced by PEDV virulent and attenuated strains.

Porcine epidemic diarrhea virus (PEDV) is an acute, highly contagious enterovirus that infects pigs of all ages. The B cells are important for antigen presentation, antibody production, and cytokine secretion to resist infection. However, the role of B cells in PEDV infection remains unclear. In this study, the effects of PEDV virulent (QY2016) and attenuated strains (CV777) on B cells sorted from neonatal piglets, nursery piglets, and gilts were investigated. The results showed that PEDV-QY2016 and PEDV-CV777 could significantly increase the expression of CD54 and CD27 in B cells from neonatal piglets. The percentages of CD80, MHC II, and IgM expressed on neonatal piglet B cells infected with PEDV-QY2016 were significantly lower than those expressed on the B cells infected with PEDV-CV777. Both PEDV-QY2016 and PEDV-CV777 could stimulate IFN-α and GM-CSF secretions in neonatal piglet B cells; IL-1, IFN-α, and IL-4 secretion in nursery piglet B cells; and IL-1, TGF-ß secretion, and GM-CSF in gilt B cells. Furthermore, both PEDV-QY2016 and PEDV-CV777 could induce the secretion of IgA, IgM, and IgG in nursery piglet B cells but could not induce the secretion of IgA, IgM, and IgG in neonatal piglet B cells. The secretion of IgA, IgM, and IgG was significantly higher by the PEDV-CV777 strains infected B cells than those by the PEDV-QY2016 strains infected gilt B cells. In conclusion, the surface molecule expression, cytokine secretion, and antibody production of B cells induced by PEDV are closely related to the ages of pigs and the virulence of the PEDV strain.

Effect of ultrasound-guided stellate ganglion block on cerebral oxygen metabolism and S100B protein during carotid endarterectomy.

OBJECTIVE: To investigate the effect of ultrasound-guided stellate ganglion block (SGB) on cerebral oxygen metabolism and serum S100B during carotid endarterectomy (CEA). METHODS: Patients who were prospectively enrolled to receive CEA under elective general anesthesia were randomized into an SGB group and a control group (ChiCTR2000033385). Before anesthesia, the SGB group underwent ipsilateral SGB under ultrasound guidance, while the control group did not. Ultrasound-guided right subclavian internal jugular vein catheterization was performed under general anesthesia. Mean arterial pressure (MAP) and heart rate (HR) were monitored at various time points (T0-T4). Arterial and internal jugular venous bulb blood were collected for blood gas analysis, determining jugular venous oxygen saturation (SjvO2), arteriovenous oxygen difference (AVDO2), cerebral oxygen extraction ratio (COER), lactate production rate (LPR), and lactate-oxygen index (LOI). The serum concentration of S100B in the internal jugular venous bulb at each time point was measured. RESULTS: The results revealed significantly lower HR during anesthesia induction and surgery in the SGB group, with more stable MAP and HR during endotracheal intubation and surgery compared to the control group (P<0.05). The control group exhibited decreases at T3 and a slight increase at T4. SjvO2 was significantly higher in the SGB group, while AVDO2 and COER gradually decreased over time, but they were significantly higher in the control group (P<0.05). LPR and LOI in both groups peaked at T3 and were significantly different between T4 and T2 (P<0.05). Serum S100B levels in both groups rose and then decreased at each time point, but they were consistently lower in the SGB group (P<0.05). CONCLUSION: SGB before CEA effectively suppresses the stress response, maintains intraoperative hemodynamic stability, improves brain tissue oxygen supply, and demonstrates a neuroprotective effect.

Pharmacokinetics of desflurane uptake and disposition in piglets.

Introduction: Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Methods: Seven piglets were administered inspiratory 6% desflurane by inhalation over 2 h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. Results: The rates of desflurane body uptake increased considerably in the initial 5 min (79.8 ml.min-1) and then declined slowly until 120 min (27.0 ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2 h, only 21.9% of the desflurane administered had been eliminated from the body. Conclusion: Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Constructing Metal(II)-Sulfate Site Catalysts toward Low Overpotential Carbon Dioxide Electroreduction to Fuel Chemicals.

Precise regulation of the active site structure is an important means to enhance the activity and selectivity of catalysts in CO2 electroreduction. Here, we creatively introduce anionic groups, which can not only stabilize metal sites with strong coordination ability but also have rich interactions with protons at active sites to modify the electronic structure and proton transfer process of catalysts. This strategy helps to convert CO2 into fuel chemicals at low overpotentials. As a typical example, a composite catalyst, CuO/Cu-NSO4/CN, with highly dispersed Cu(II)-SO4 sites has been reported, in which CO2 electroreduction to formate occurs at a low overpotential with a high Faradaic efficiency (-0.5 V vs. RHE, FEformate=87.4 %). Pure HCOOH is produced with an energy conversion efficiency of 44.3 % at a cell voltage of 2.8 V. Theoretical modeling demonstrates that sulfate promotes CO2 transformation into a carboxyl intermediate followed by HCOOH generation, whose mechanism is significantly different from that of the traditional process via a formate intermediate for HCOOH production.

Effects of porcine epidemic diarrhea virus infection on CD21+ B cells activation.

Porcine epidemic diarrhea virus (PEDV) is a devastating pathogen of acute- gastrointestinal infectious diseases, which can cause vomiting, diarrhea, dehydration and high morbidity and mortality among neonatal piglets. Humoral immunity plays a vital role in the host anti-PEDV infection process, but the mechanism of PEDV-induced B-cell immune response remains unknown. In this study, the effects of PEDV infection on CD21+ B cell activation were systematically analyzed through animal experiments. Enzyme-linked immunosorbent assays (ELISA) revealed that low levels of serum-specific IgA, IgM, or IgG were detected in piglets after PEDV infection, respectively. Serum interleukin (IL)-6 levels increased significantly at 4 d after infection, and the levels of IL-4, B-cell activating factor (BAFF), interferon (IFN)-γ, transforming growth factor (TGF)-ß and IL-10 decreased at 7 d after infection. Fluorescence-activated cell sorting (FACS) showed that expression levels of CD21, MHC Ⅱ, CD40, and CD38 on B cell surfaces were significantly higher. In contrast, the proportions of CD21+IgM+ B cells were decreased in peripheral blood mononuclear cells (PBMCs) from the infected piglets. No differences were found in the percentage of CD21+CD80+ and CD21+CD27+ B cells in PBMCs from the infected piglets. In addition, the number of CD21+B cells in PBMCs stimulated with PEDV in vitro was significantly lower. No significant change in the mRNA expression of BCR molecules was found while the expression levels of paired immunoglobulin-like receptor B (PIR-B), B cell adaptor molecule of 32 kDa (Bam32) and BAFF were decreased. In conclusion, our research demonstrates that virulent strains of PEDV profoundly impact B cell activation, leading to alterations in phenotypic expression and BCR signaling molecules. Furthermore, this dysregulation results in compromised specific antibody secretion and perturbed cytokine production, highlighting the intricate immunological dysfunctions induced by PEDV infection.

Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition.

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.