A 10-year in-depth follow-up of post-lingual hearing loss patients with Chinese domestic cochlear implants.

BACKGROUND: Follow-up of cochlear implant effectiveness is mainly focused on 3 years postoperatively, and studies with more than 5 years of observation are rare, especially for local Chinese brands. OBJECTIVES: Nurotron (Chinese domestic cochlear implant brand) CI recipients who participated in the clinical trial in 2009 were followed-up for 10 years prospectively, providing data to guide doctors and patients. MATERIAL AND METHODS: From December 2009 to April 2010, 57 subjects underwent Nurotron Venus CI surgery at multiple-centers, and were continued to be followed up and assessed at 1, 2, 3, 4, 5, and 10 years after switch on. RESULTS: All recipients were successfully implanted with CIs with no difficulty in subsequent use with one reported case of re-implantation at 9 years after implantation. The aided hearing thresholds were significantly improved at one month after switch on (p < 0.0001) and remained stable afterwards for 10 years. Speech recognition scores were significantly higher than pre-operative results (p < 0.05) and continued to improve till 3 years after switch on. At 10 years post-operation, most subjects had improved QOL scores in most sub-items. CONCLUSIONS AND SIGNIFICANCE: Nurotron Venus CI System provides long-term, stable results in hearing speech assistance capabilities and can improve the quality of life of CI recipients.

Origin of Chemoselectivity of Halohydrin Dehalogenase-Catalyzed Epoxide Ring-Opening Reactions.

By performing molecular dynamics (MD), quantum mechanical/molecular mechanical (QM/MM) calculations, and QM cluster calculations, the origin of chemoselectivity of halohydrin dehalogenase (HHDH)-catalyzed ring-opening reactions of epoxide with the nucleophilic reagent NO2- has been explored. Four possible chemoselective pathways were considered, and the computed results indicate that the pathway associated with the nucleophilic attack on the Cα position of epoxide by NO2- is most energetically favorable and has an energy barrier of 12.9 kcal/mol, which is close to 14.1 kcal/mol derived from experimental kinetic data. A hydrogen bonding network formed by residues Ser140, Tyr153, and Arg157 can strengthen the electrophilicity of the active site of the epoxide substrate to affect chemoselectivity. To predict the energy barrier trends of the chemoselective transition states, multiple analyses including distortion analysis and electrophilic Parr function (Pk+) analysis were carried out with or without an enzyme environment. The obtained insights should be valuable for the rational design of enzyme-catalyzed and biomimetic organocatalytic epoxide ring-opening reactions with special chemoselectivity.

Circulating HMGB1 in acute ischemic stroke and its association with post-stroke cognitive impairment.

Background: Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke. Objective: To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up. Methods: A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters. Results: Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ± 1.2 ng/mL vs 4.6 ± 0.5 ng/mL, respectively; p < 0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p < 0.001). Conclusion: Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions.

SARS-CoV-2 omicron BA.2.87.1 exhibits higher susceptibility to serum neutralization than EG.5.1 and JN.1.

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

Crucial gating residues govern the enhancement of peroxygenase activity in an engineered cytochrome P450 O-demethylase.

P450-catalyzed O-demethylation reactions have recently attracted particular attention because of their potential applications in lignin bioconversion. We recently enabled the peroxygenase activity of CYP199A4, a NADH-dependent cytochrome P450 monooxygenase from Rhodopseudomonas palustris, by engineering a hydrogen peroxide (H2O2) tunnel. In this report, we reveal by crystallography and molecule dynamics simulations that key residues located at one of the water tunnels in CYP199A4 play a crucial gating role, which enhances the peroxygenase activity by regulating the inflow of H2O2. These results provide a more complete understanding of the mechanism by which monooxygenase is converted into peroxygenase activity through the H2O2 tunnel engineering (HTE) strategy. Furthermore, a library of engineered CYP199A4 peroxygenases was constructed to explore their application potentials for O-demethylation of various methoxy-substituted benzoic acid derivatives. The engineered CYP199A4 peroxygenases showed good functional group tolerance and preferential O-demethylation at the meta- or para-position, indicating potential O-demethylation of H- and G-type lignin monomers. This work reveals the feasibility of the HTE strategy in creating P450 peroxygenase from a mechanistic perspective, laying the foundation for developing an effective P450 O-demethylase applicable in lignin bioconversion.

Using network pharmacology to discover potential drugs for hypertrophic scars.

BACKGROUND: Hypertrophic scar is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation, and existing drugs cannot achieve satisfactory therapeutic effects. OBJECTIVES: This study aimed to explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for hypertrophic scars. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, transforming growth factor ß (TGF-ß) signaling pathway, and other biological pathways. Integrin ß1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib, and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and pro-fibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA (siRNA) can also inhibit mouse scar hyperplasia. CONCLUSIONS: ITGB1 and TGF-ß signaling pathways are important for hypertrophic scar formation. Crizotinib could serve as a potential drug for hypertrophic scars.

Cerebrospinal fluid CXCL13 concentration for diagnosis of neurosyphilis: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library and Web of Science databases from their inception until 1 May 2023. ELIGIBILITY CRITERIA: Both cross-sectional and case-control diagnostic test studies evaluating the diagnostic value of CSF CXCL13 in diagnosing neurosyphilis were included, with no language restrictions. DATA EXTRACTION AND SYNTHESIS: Two researchers extracted data independently from all finally included articles. The updated Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. Quantitative synthesis was done using a bivariate random-effects model. RESULTS: This meta-analysis included seven eligible studies involving a total of 1152 patients with syphilis and 430 patients with neurosyphilis. The pooled sensitivity, specificity and summary area under the curve (AUC) of CSF CXCL13 testing for the diagnosis of neurosyphilis were 0.76 (95% CI 0.64 to 0.85; I2=82%), 0.83 (95% CI 0.80 to 0.85; I2=32.29%) and 0.84 (95% CI 0.81 to 0.87), respectively. Sensitivity analysis confirmed the stability of the combined results. Meta-regression analysis revealed that the heterogeneity of pooled sensitivity was related to different study regions; subgroup analysis indicated that the diagnostic value of CSF CXCL13 testing reported in studies from China was superior to that reported in non-Chinese studies (pooled sensitivity, specificity and summary AUC values were 0.84 (I2=0) vs 0.64 (I2=79.53%), 0.83 (I2=42.03%) vs 0.83 (I2=32.87%) and 0.87 vs 0.83, respectively). The diagnostic value reported in studies with a sample size ≥200, unclassified neurosyphilis and HIV-negative subgroups was superior to the total combined value. CONCLUSIONS: This meta-analysis has demonstrated a reasonable level of accuracy for diagnosis of neurosyphilis with CSF CXCL13 testing. Further multicentre, prospective diagnostic studies, especially in asymptomatic neurosyphilis and HIV-infected patients, are needed to provide more evidence for evaluation before clinical application. PROSPERO REGISTRATION NUMBER: CRD42023414212.

Organic Ligand-Mediated Dissolution and Fractionation of Rare-Earth Elements (REEs) from Carbonate and Phosphate Minerals.

Global efforts to build a net-zero economy and the irreplaceable roles of rare-earth elements (REEs) in low-carbon technologies urge the understanding of REE occurrence in natural deposits, discovery of alternative REE resources, and development of green extraction technologies. Advancement in these directions requires comprehensive knowledge on geochemical behaviors of REEs in the presence of naturally prevalent organic ligands, yet much remains unknown about organic ligand-mediated REE mobilization/fractionation and related mechanisms. Herein, we investigated REE mobilization from representative host minerals induced by three representative organic ligands: oxalate, citrate, and the siderophore desferrioxamine B (DFOB). Reaction pH conditions were selected to isolate the ligand-complexation effect versus proton dissolution. The presence of these organic ligands displayed varied impacts, with REE dissolution remarkably enhanced by citrate, mildly promoted by DFOB, and showing divergent effects in the presence of oxalate, depending on the mineral type and reaction pH. Thermodynamic modeling indicates the dominant presence of REE-ligand complexes under studied conditions and suggests ligand-promoted REE dissolution to be the dominant mechanism, consistent with experimental data. In addition, REE dissolution mediated by these ligands exhibited a distinct fractionation toward heavy REE (HREE) enrichment in the solution phase, which can be mainly attributed to the formation of thermodynamically predicted more stable HREE-ligand complexes. The combined thermodynamic modeling and experimental approach provides a framework for the systematic investigation of REE mobilization, distribution, and fractionation in the presence of organic ligands in natural systems and for the design of green extraction technologies.

Structures, fundamental properties, and potential applications of low-dimensional C60 polymers and other nanocarbons: a review.

Since carbon (C) atom has a variety of chemical bonds via hybridization between s and p atomic orbitals, it is well known that there are robust carbon materials. In particular, discovery of C60 has been an epoch making to cultivate nanocarbon fields. Since then, nanocarbon materials such as nanotube and graphene have been reported. It is interesting to note that C60 is soluble and volatile unlike nanotube and graphene. This indicates that C60 film is easy to be produced on any kinds of substrates, which is advantage for device fabrication. In particular, electron-/photo-induced C60 polymerization finally results in formation of one-dimensional (1D) metallic peanut-shaped and 2D dumbbell-shaped semiconducting C60 polymers, respectively. This enables us to control the physicochemical properties of C60 films using electron-/photo-lithography techniques. In this review, we focused on the structures, fundamental properties, and potential applications of the low-dimensional C60 polymers and other nanocarbons such as C60 peapods, wavy-structured graphene, and penta-nanotubes with topological defects. We hope this review will provide new insights for producing new novel nanocarbon materials and inspire broad readers to cultivate new further research in carbon materials.

We review the structures, fundamental properties, and applications of low-dimensional C₆₀ polymers and other related nanocarbons such as C₆₀ peapods, wavy-structured graphene, and penta-nanotubes from a standpoint of topological defects.

Upgrading Gel Electrolytes Through Electrostatic-Induced Dual-Salt Paradigm for Superior Zn-Ion Battery Performance.

Gel electrolytes are gaining attention for rechargeable Zn-ion batteries because of their high safety, high flexibility, and excellent comprehensive electrochemical performances. However, current gel electrolytes still perform at mediocre levels due to incomplete Zn salts dissociation and side reactions. Herein, an electrostatic-induced dual-salt strategy is proposed to upgrade gel electrolytes to tackle intrinsic issues of Zn metal anodes. The competitive coordination mechanism driven by electrostatic repulsion and steric hindrance of dual anions promotes zinc salt dissociation at low lithium salt addition levels, improving ion transport and mechanical properties of gel electrolytes. Li+ ions and gel components coordinate with H2O, reducing active H2O molecules and inhibiting associated side reactions. The dual-salt gel electrolyte enables excellent reversibility of Zn anodes at both room and low temperatures. Zn||Polyaniline cells using the dual-salt gel electrolyte exhibit a high discharge capacity of 180 mAh g-1 and long-term cycling stability over 180 cycles at -20 °C. The dual-salt strategy offers a cost-effective approach to improving gel electrolytes for high-performance flexible Zn-ion batteries.

Development of an assessment tool for designated medical institutions in China--Based on the application of an online assessment system.

Background: Due to the expanding coverage of medical insurance and the growth of medical expenses, the ability to assess the performance of designated medical institutions (DMIs) in supporting the delivery of high-quality patient care and the standardized use of funds represents a priority in China. Despite such interest, there has yet to be an operable standard and labor-saving method for assessing DMIs in China. Objective: The main objectives include two aspects: (1) establishing an evaluation index system for DMIs based on contracts; (2) designing and developing an online evaluation platform. Methods: A group of 20 experts with theoretical and practical expertise in medical insurance regulation and performance evaluation were invited to select available indicators. A combination weighting method based on analytic hierarchy process and entropy method was used to determine the weight coefficient. Shanghai was taken as the sample area, and 760 DMIs were included in the empirical research. The test-retest reliability method and criterion-related validity method was used to test the reliability and the validity of the evaluation result. Results: An assessment index system that included 6 domains and 56 indicators was established in this study. Furthermore, we developed an online platform to assist in the implementation of the assessment. The results showed that the average score of assessment was 94.39, the median was 96.92. The test-retest reliability value was 0.96 (P ≤ 0.01), which indicated high stability of the assessment. In addition, there was a significant negative relationship between assessment score and the penalty amount of DMIs (R = -0.133, P < 0.001). After adjusting for the basic characteristics of medical institutions, the number of visits and revenue, the negative relationship was still significant (B = -0.080, P < 0.05). These results are consistent with expectations, indicating that the assessment had good criterion-related validity. Conclusions: This study established an operable assessment measure and developed an online platform to assess the performance of DMIs. The results showed good feasibility and reliability in empirical research. Our research findings provided an operable Chinese solution for DMI assessment that saves manpower and time, which would have good enlightening significance in other regions of China and in low-income and middle-income countries internationally.

Bimetallic MOFs-Derived NiFe2O4/Fe2O3 Enabled Dendrite-free Lithium Metal Anodes with Ultra-High Area Capacity Based on An Intermittent Lithium Deposition Model.

In practical operating conditions, the lithium deposition behavior is often influenced by multiple coupled factors and there is also a lack of comprehensive and long-term validation for dendrite suppression strategies. Our group previously proposed an intermittent lithiophilic model for high-performance three-dimensional (3D) composite lithium metal anode (LMA), however, the electrodeposition behavior was not discussed. To verify this model, this paper presents a modified 3D carbon cloth (CC) backbone by incorporating NiFe2O4/Fe2O3 (NFFO) nanoparticles derived from bimetallic NiFe-MOFs. Enhanced Li adsorption capacity and lithiophilic modulation were achieved by bimetallic MOFs-derivatives which prompted faster and more homogeneous Li deposition. The intermittent model was further verified in conjunction with the density functional theory (DFT) calculations and electrodeposition behaviors. As a result, the obtained Li-CC@NFFO||Li-CC@NFFO symmetric batteries exhibit prolonged lifespan and low hysteresis voltage even under ultra-high current and capacity conditions (5 mA cm-2, 10 mAh cm-2), what's more, the full battery coupled with a high mass loading (9 mg cm-2) of LiFePO4 cathode can be cycled at a high rate of 5C, the capacity retention is up to 95.2% before 700 cycles. This work is of great significance to understand the evolution of lithium dendrites on the 3D intermittent lithiophilic frameworks.

Controlled Size Characterization Process for In-Situ TiB2 Particles from Al Matrix Composites Using Nanoparticle Size Analysis.

The wide size range and high tendency to agglomerate of in-situ TiB2 particles in reinforced Al matrix composites introduce great difficulties in their size characterization. In order to use a nanoparticle size analyzer (NSA) to obtain the precise size distribution of TiB2 particles, a controlled size characterization process has been explored. First, the extraction and drying processes for TiB2 particles were optimized. In the extraction process, alternated applications of magnetic stirring and normal ultrasound treatments were proven to accelerate the dissolution of the Al matrix in HCl solution. Furthermore, freeze-drying was found to minimize the agglomeration tendency among TiB2 particles, facilitating the acquisition of pure powders. Such powders were quantitatively made into an initial TiB2 suspension. Second, the chemical and physical dispersion technologies involved in initial TiB2 suspension were put into focus. Chemically, adding PEI (M.W. 10000) at a ratio of mPEI/mTiB2 = 1/30 into the initial suspension can greatly improve the degree of TiB2 dispersion. Physically, the optimum duration for high-energy ultrasound application to achieve TiB2 dispersion was 10 min. Overall, the corresponding underlying dispersion mechanisms were discussed in detail. With the combination of these chemical and physical dispersion specifications for TiB2 suspension, the bimodal size distribution of TiB2 was able to be characterized by NSA for the first time, and its number-average diameter was 111 ± 6 nm, which was reduced by 59.8% over the initial suspension. Indeed, the small-sized and large-sized peaks of the TiB2 particles characterized by NSA mostly match the results obtained from transmission electron microscopy and scanning electron microscopy, respectively.

Comparative genomic analyses provide insight into the pathogenicity of three Pseudomonas syringae pv. actinidiae strains from Anhui Province, China.

BACKGROUND: Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. RESULTS: Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. CONCLUSION: Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic - China, September 2022-August 2023.

What is already known about this topic?: Mucosal IgA plays a crucial role in host immunity against respiratory viruses. Recent studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. However, a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019 (COVID-19) pandemic is yet to be conducted. What is added by this report?: In our study involving 3,421 participants, we documented IgA responses subsequent to SARS-CoV-2 infection. A significant proportion of individuals sustained increased levels of IgA for over six months. These levels were also observed in individuals with prior infections who underwent asymptomatic reinfections, indicating an active production of IgA antibodies. Further, individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after recovery. What are the implications for public health practice?: IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 infection. These insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models.

Purpose: Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response. Methods: To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively. Results: We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae. Conclusion: Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.

Adrenomedullin improved endothelial dysfunction via receptor-Akt pathway in rats with obesity-related hypertension.

Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.

Multifunctional Nanocomposite Yield-Stress Fluids for Printable and Stretchable Electronics.

Compliant materials are crucial for stretchable electronics. Stretchable solids and gels have limitations in deformability and durability, whereas active liquids struggle to create complex devices. This study presents multifunctional yield-stress fluids as printable ink materials to construct stretchable electronic devices. Ionic nanocomposites comprise silica nanoparticles and ion liquids, while electrical nanocomposites use the natural oxidation of liquid metals to produce gallium oxide nanoflake additives. These nanocomposite inks can be printed on an elastomer substrate and stay in a solid state for easy encapsulation. However, their transition into a liquid state during stretching allows ultrahigh deformability up to the fracture strain of the elastomer. The ionic inks produce strain sensors with high stretchability and temperature sensors with high sensitivity of 7% °C-1. Smart gloves are further created by integrating these sensors with printed electrical interconnects, demonstrating bimodal detection of temperatures and hand gestures. The nanocomposite yield-stress fluids combine the desirable qualities of solids and liquids for stretchable devices and systems.

Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis: A case report.

BACKGROUND: According to the latest report, colorectal cancer is still one of the most prevalent cancers, with the third highest incidence and mortality worldwide. Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory, especially for mismatch repair proficient (pMMR) rectal cancer, which leads to poor prognosis and recurrence. CASE SUMMARY: We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes, including the left supraclavicular lymph node, before treatment in a 70-year-old man. He received full courses of chemoradiotherapy (CRT) followed by 4 cycles of programmed death 1 inhibitor Tislelizumab, and a pathologic complete response (pCR) was achieved, and the lesion of the left supraclavicular lymph node also disappeared. CONCLUSION: pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.