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1.
Nat Commun ; 15(1): 5461, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937433

ABSTRACT

Peptidoglycan (PG) sacculi surround the cytoplasmic membrane, maintaining cell integrity by withstanding internal turgor pressure. During cell growth, PG endopeptidases cleave the crosslinks of the fully closed sacculi, allowing for the incorporation of new glycan strands and expansion of the peptidoglycan mesh. Outer-membrane-anchored NlpI associates with hydrolases and synthases near PG synthesis complexes, facilitating spatially close PG hydrolysis. Here, we present the structure of adaptor NlpI in complex with the endopeptidase MepS, revealing atomic details of how NlpI recruits multiple MepS molecules and subsequently influences PG expansion. NlpI binding elicits a disorder-to-order transition in the intrinsically disordered N-terminal of MepS, concomitantly promoting the dimerization of monomeric MepS. This results in the alignment of two asymmetric MepS dimers respectively located on the two opposite sides of the dimerization interface of NlpI, thus enhancing MepS activity in PG hydrolysis. Notably, the protein level of MepS is primarily modulated by the tail-specific protease Prc, which is known to interact with NlpI. The structure of the Prc-NlpI-MepS complex demonstrates that NlpI brings together MepS and Prc, leading to the efficient MepS degradation by Prc. Collectively, our results provide structural insights into the NlpI-enabled avidity effect of cellular endopeptidases and NlpI-directed MepS degradation by Prc.


Subject(s)
Endopeptidases , Lipoproteins , Peptidoglycan , Peptidoglycan/metabolism , Endopeptidases/metabolism , Endopeptidases/chemistry , Lipoproteins/metabolism , Lipoproteins/chemistry , Protein Binding , Protein Multimerization , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Models, Molecular , Crystallography, X-Ray , Hydrolysis , Escherichia coli/metabolism
2.
J Am Heart Assoc ; 13(13): e033997, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38904231

ABSTRACT

BACKGROUND: Insulin resistance (IR) is closely linked to cardiometabolic diseases. Preventing and improving IR in nondiabetic populations is critically important. We aimed to investigate the relationship between Life's Essential 8 (LE8), the latest tool from the American Heart Association quantifying cardiovascular health, and IR among nondiabetic populations in the United States. METHODS AND RESULTS: This cross-sectional study used data on 11 246 nondiabetic adults aged ≥20 years from the 2005 to 2018 the National Health and Nutrition Examination Survey. The LE8 score was classified into 2 subscale scores: health factor score and health behavior score. IR was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Weighted logistic and linear regression models analyzed associations among the LE8 score, health behavior score, health factor score, and IR. Restricted cubic spline models assessed dose-response relationships. Adjusted subgroup analyses and inverse probability of treatment weighting method also evaluated the LE8-IR relationship. Of the 11 246 participants, 4860 (43.2%) had IR. The mean LE8 score was 70.07 (95% CI, 69.57-70.58). In fully adjusted models, higher LE8 scores were associated with lower IR odds (odds ratio per 10-unit increase, 0.57 [95% CI, 0.54-0.61]). Nonlinear LE8-IR dose-response was observed. Similar patterns were seen for health behavior and health factor subscores, with stronger IR correlations for health factors. The inverse LE8-IR association was significantly more pronounced among White participants and those with higher education, higher income, and without hypertension, cardiovascular disease, or chronic kidney disease. Significant negative LE8-IR associations persisted after inverse probability of treatment weighting. CONCLUSIONS: LE8 and subscale scores are negatively associated with IR in a nonlinear relationship. Promoting optimal cardiovascular health adherence may improve IR in nondiabetic populations.


Subject(s)
Insulin Resistance , Nutrition Surveys , Humans , Insulin Resistance/physiology , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , United States/epidemiology , Health Behavior , Cardiovascular Diseases/epidemiology , Risk Factors , Risk Assessment , Aged , Young Adult
3.
Front Oncol ; 14: 1364997, 2024.
Article in English | MEDLINE | ID: mdl-38887238

ABSTRACT

Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.

5.
Transplant Proc ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38890074

ABSTRACT

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.

6.
Vaccines (Basel) ; 12(6)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38932417

ABSTRACT

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

7.
Am J Clin Pathol ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941215
8.
ACS Nano ; 18(26): 17031-17040, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38874427

ABSTRACT

The formation of uniform, nondendritic seeds is essential to realizing dense lithium (Li) metal anodes and long-life batteries. Here, we discover that faceted Li seeds with a hexagonal shape can be uniformly grown on carbon-polymer composite films. Our investigation reveals the critical role of carbon defects in serving as the nucleation sites for their formation. Tuning the density and spatial distribution of defects enables the optimization of conditions for faceted seed growth. Raman spectral results confirm that lithium nucleation indeed starts at the defect sites. The uniformly distributed crystalline seeds facilitate low-porosity Li deposition, effectively reducing Li pulverization during cycling and unlocking the fast-charging ability of Li metal batteries. At a 1 C rate, full cells using LiNi0.8Mn0.1Co0.1O2 cathode (4.5 mA h cm-2) paired with a lithium anode grown on carbon composite films achieve a 313% improvement in cycle life compared to baseline cells. Polymer composites with carbonaceous materials rich in defects are scalable, low-cost substrates for high-rate, high-energy-density batteries.

9.
Biochem Biophys Res Commun ; 721: 150109, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38762932

ABSTRACT

Wild-type Proteinase K binds to two Ca2+ ions, which play an important role in regulating enzymaticactivity and maintaining protein stability. Therefore, a predetermined concentration of Ca2+ must be added during the use of Proteinase K, which increases its commercial cost. Herein, we addressed this challenge using a computational strategy to engineer a Proteinase K mutant that does not require Ca2+ and exhibits high enzymatic activity and protein stability. In the absence of Ca2+, the best mutant, MT24 (S17W-S176N-D260F), displayed an activity approximately 9.2-fold higher than that of wild-type Proteinase K. It also exhibited excellent protein stability, retaining 56.2 % of its enzymatic activity after storage at 4 °C for 5 days. The residual enzymatic activity was 65-fold higher than that of the wild-type Proteinase K under the same storage conditions. Structural analysis and molecular dynamics simulations suggest that the introduction of new hydrogen bond and π-π stacking at the Ca2+ binding sites due to the mutation may be the reasons for the increased enzymatic activity and stability of MT24.


Subject(s)
Calcium , Endopeptidase K , Enzyme Stability , Molecular Dynamics Simulation , Protein Stability , Endopeptidase K/metabolism , Endopeptidase K/chemistry , Calcium/metabolism , Calcium/chemistry , Computer-Aided Design , Mutation , Binding Sites , Protein Engineering/methods , Protein Conformation
10.
Sci Adv ; 10(20): eadi7024, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758791

ABSTRACT

At the synapse, presynaptic neurotransmitter release is tightly controlled by release machinery, involving the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and Munc13. The Ca2+ sensor Doc2 cooperates with Munc13 to regulate neurotransmitter release, but the underlying mechanisms remain unclear. In our study, we have characterized the binding mode between Doc2 and Munc13 and found that Doc2 originally occludes Munc13 to inhibit SNARE complex assembly. Moreover, our investigation unveiled that EphB2, a presynaptic adhesion molecule (SAM) with inherent tyrosine kinase functionality, exhibits the capacity to phosphorylate Doc2. This phosphorylation attenuates Doc2 block on Munc13 to promote SNARE complex assembly, which functionally induces spontaneous release and synaptic augmentation. Consistently, application of a Doc2 peptide that interrupts Doc2-Munc13 interplay impairs excitatory synaptic transmission and leads to dysfunction in spatial learning and memory. These data provide evidence that SAMs modulate neurotransmitter release by controlling SNARE complex assembly.


Subject(s)
Calcium-Binding Proteins , Nerve Tissue Proteins , Neurotransmitter Agents , Receptor, EphB2 , SNARE Proteins , Synaptic Transmission , SNARE Proteins/metabolism , Animals , Neurotransmitter Agents/metabolism , Nerve Tissue Proteins/metabolism , Phosphorylation , Receptor, EphB2/metabolism , Receptor, EphB2/genetics , Calcium-Binding Proteins/metabolism , Protein Binding , Humans , Mice , Rats
11.
Anal Chem ; 96(22): 9051-9059, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38776068

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.


Subject(s)
Gold , Graphite , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Gold/chemistry , Graphite/chemistry , Humans , Metal Nanoparticles/chemistry , Surface Properties , Amino Acids/analysis , Amino Acids/chemistry
12.
Biophys Rep ; 10(1): 31-40, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38737475

ABSTRACT

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNAER) family proteins are the engines of most intra-cellular and exocytotic membrane fusion pathways (Jahn and Scheller 2006). Over the past two decades, in-vitro liposome fusion has been proven to be a powerful tool to reconstruct physiological SNARE-mediated membrane fusion processes (Liu et al. 2017). The reconstitution of the membrane fusion process not only provides direct evidence of the capability of the cognate SNARE complex in driving membrane fusion but also allows researchers to study the functional mechanisms of regulatory proteins in related pathways (Wickner and Rizo 2017). Heretofore, a variety of delicate methods for in-vitro SNARE-mediated liposome fusion have been established (Bao et al. 2018; Diao et al. 2012; Duzgunes 2003; Gong et al. 2015; Heo et al. 2021; Kiessling et al. 2015; Kreye et al. 2008; Kyoung et al. 2013; Liu et al. 2017; Scott et al. 2003). Although technological advances have made reconstitution more physiologically relevant, increasingly elaborate experimental procedures, instruments, and data processing algorithms nevertheless hinder the non-experts from setting up basic SNARE-mediated liposome fusion assays. Here, we describe a low-cost, timesaving, and easy-to-handle protocol to set up a foundational in-vitro SNARE-mediated liposome fusion assay based on our previous publications (Liu et al. 2023; Wang and Ma 2022). The protocol can be readily adapted to assess various types of SNARE-mediated membrane fusion and the actions of fusion regulators by using appropriate alternative additives (e.g., proteins, macromolecules, chemicals, etc.). The total time required for one round of the assay is typically two days and could be extremely compressed into one day.

13.
Front Cell Infect Microbiol ; 14: 1341332, 2024.
Article in English | MEDLINE | ID: mdl-38746783

ABSTRACT

Introduction: The Crimean-Congo hemorrhagic fever virus (CCHFV), the most geographically widespread tick-borne virus, is endemic in Africa, Eastern Europe and Asia, with infection resulting in mortality in up to 30% of cases. Currently, there are no approved vaccines or effective therapies available for CCHF. The CCHFV should only be manipulated in the BSL-4 laboratory, which has severely hampered basic seroprevalence studies. Methods: In the present study, two antibody detection methods in the forms of an enzyme-linked immunosorbent assay (ELISA) and a surrogate virus neutralization test (sPVNT) were developed using a recombinant glycoprotein (rGP) and a vesicular stomatitis virus (VSV)-based virus bearing the CCHFV recombinant glycoprotein (rVSV/CCHFV) in a biosafety level 2 (BSL-2) laboratory, respectively. Results: The rGP-based ELISA and rVSV/CCHFV-based sVNT were established by using the anti-CCHFV pre-GC mAb 11E7, known as a broadly cross-reactive, potently neutralizing antibody, and their applications as diagnostic antigens were validated for the specific detection of CCHFV IgG and neutralizing antibodies in experimental animals. In two tests, mAb clone 11E7 (diluted at 1:163840 or 512) still displayed positive binding and neutralization, and the presence of antibodies (IgG and neutralizing) against the rGP and rVSV/CCHFV was also determined in the sera from the experimental animals. Both mAb 11E7 and animal sera showed a high reactivity to both antigens, indicating that bacterially expressed rGP and rVSV/CCHFV have good immunoreactivity. Apart from establishing two serological testing methods, their results also demonstrated an imperfect correlation between IgG and neutralizing antibodies. Discussion: Within this limited number of samples, the rGP and rVSV/CCHFV could be safe and convenient tools with significant potential for research on specific antibodies and serological samples.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , Hemorrhagic Fever Virus, Crimean-Congo , Hemorrhagic Fever, Crimean , Immunoglobulin G , Neutralization Tests , Hemorrhagic Fever Virus, Crimean-Congo/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Neutralization Tests/methods , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , Immunoglobulin G/immunology , Hemorrhagic Fever, Crimean/diagnosis , Hemorrhagic Fever, Crimean/immunology , Animals , Humans , Glycoproteins/immunology , Serologic Tests/methods , Recombinant Proteins/immunology , Mice , Antibodies, Monoclonal/immunology
14.
Sensors (Basel) ; 24(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732808

ABSTRACT

Currently, surface EMG signals have a wide range of applications in human-computer interaction systems. However, selecting features for gesture recognition models based on traditional machine learning can be challenging and may not yield satisfactory results. Considering the strong nonlinear generalization ability of neural networks, this paper proposes a two-stream residual network model with an attention mechanism for gesture recognition. One branch processes surface EMG signals, while the other processes hand acceleration signals. Segmented networks are utilized to fully extract the physiological and kinematic features of the hand. To enhance the model's capacity to learn crucial information, we introduce an attention mechanism after global average pooling. This mechanism strengthens relevant features and weakens irrelevant ones. Finally, the deep features obtained from the two branches of learning are fused to further improve the accuracy of multi-gesture recognition. The experiments conducted on the NinaPro DB2 public dataset resulted in a recognition accuracy of 88.25% for 49 gestures. This demonstrates that our network model can effectively capture gesture features, enhancing accuracy and robustness across various gestures. This approach to multi-source information fusion is expected to provide more accurate and real-time commands for exoskeleton robots and myoelectric prosthetic control systems, thereby enhancing the user experience and the naturalness of robot operation.


Subject(s)
Electromyography , Gestures , Neural Networks, Computer , Humans , Electromyography/methods , Signal Processing, Computer-Assisted , Pattern Recognition, Automated/methods , Acceleration , Algorithms , Hand/physiology , Machine Learning , Biomechanical Phenomena/physiology
15.
Opt Express ; 32(6): 10419-10428, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571254

ABSTRACT

Twisted stacking of two-dimensional materials with broken inversion symmetry, such as spiral MoTe2 nanopyramids and supertwisted spiral WS2, emerge extremely strong second- and third-harmonic generation. Unlike well-studied nonlinear optical effects in these newly synthesized layered materials, photoluminescence (PL) spectra and exciton information involving their optoelectronic applications remain unknown. Here, we report layer- and power-dependent PL spectra of the supertwisted spiral WS2. The anomalous layer-dependent PL evolutions that PL intensity almost linearly increases with the rise of layer thickness have been determined. Furthermore, from the power-dependent spectra, we find the power exponents of the supertwisted spiral WS2 are smaller than 1, while those of the conventional multilayer WS2 are bigger than 1. These two abnormal phenomena indicate the enlarged interlayer spacing and the decoupling interlayer interaction in the supertwisted spiral WS2. These observations provide insight into PL features in the supertwisted spiral materials and may pave the way for further optoelectronic devices based on the twisted stacking materials.

16.
Front Endocrinol (Lausanne) ; 15: 1322969, 2024.
Article in English | MEDLINE | ID: mdl-38654927

ABSTRACT

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.


Subject(s)
Acute Coronary Syndrome , Biomarkers , Diabetes Mellitus , Percutaneous Coronary Intervention , Thyroxine , Triiodothyronine , Humans , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/surgery , Male , Female , Triiodothyronine/blood , Percutaneous Coronary Intervention/adverse effects , Middle Aged , Prognosis , Thyroxine/blood , Aged , Biomarkers/blood , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Thyroid Function Tests , Follow-Up Studies
17.
J Colloid Interface Sci ; 667: 543-552, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38657538

ABSTRACT

The electrocatalytic production of "green hydrogen", such as through the electrolysis of water or urea has been vigorously advocated to alleviate the energy crisis. However, their electrode reactions including oxygen evolution reaction (OER), urea oxidation reaction (UOR), and hydrogen evolution reaction (HER) all suffer from sluggish kinetics, which urgently need catalysts to accelerate the processes. Herein, we design and prepare an OER/UOR/HER trifunctional catalyst by transforming the homemade CoO nanorod into a two-dimensional (2D) ultrathin heterojunction nickel-iron-cobalt hybrid phosphides nanosheet (NiFeP/CoP) via a hydrothermal-phosphorization method. Consequently, a strong electronic interaction was found among the Ni2P/FeP4/CoP heterogeneous interfaces, which regulates the electronic structure. Besides the high mass transfer property of 2D nanosheet, Ni2P/FeP4/CoP displays improved OER/UOR/HER performance. At 10 mA cm-2, the OER overpotential reaches 274 mV in 1.0 M KOH, and the potential of UOR is only 1.389 V in 1.0 M KOH and 0.33 M urea. More strikingly, the two-electrode systems for electrolysis water and urea-assisted electrolysis water assembled by NiFeP/CoP could maintain long-term stability for 35 h and 12 h, respectively. This work may help to pave the way for upcoming research horizons of multifunctional electrocatalysts.

18.
Zhen Ci Yan Jiu ; 49(4): 331-340, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649200

ABSTRACT

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.


Subject(s)
Acupuncture Therapy , Arthritis, Experimental , Chemokine CXCL1 , Receptors, Interleukin-8B , Somatosensory Cortex , Animals , Humans , Male , Mice , Rats , Acupuncture Points , Arthritis, Experimental/therapy , Arthritis, Experimental/metabolism , Arthritis, Experimental/genetics , Chemokine CXCL1/metabolism , Chemokine CXCL1/genetics , Inflammation/therapy , Inflammation/metabolism , Inflammation/genetics , Mice, Inbred BALB C , Pain/metabolism , Pain/genetics , Pain Management , Rats, Wistar , Receptors, Interleukin-8B/metabolism , Receptors, Interleukin-8B/genetics , Signal Transduction , Somatosensory Cortex/metabolism
19.
Sci Rep ; 14(1): 8302, 2024 04 09.
Article in English | MEDLINE | ID: mdl-38594313

ABSTRACT

We aim to develop machine learning (ML) models for predicting the complexity and mortality of polytrauma patients using clinical features, including physician diagnoses and physiological data. We conducted a retrospective analysis of a cohort comprising 756 polytrauma patients admitted to the intensive care unit (ICU) at Pizhou People's Hospital Trauma Center, Jiangsu, China between 2020 and 2022. Clinical parameters encompassed demographics, vital signs, laboratory values, clinical scores and physician diagnoses. The two primary outcomes considered were mortality and complexity. We developed ML models to predict polytrauma mortality or complexity using four ML algorithms, including Support Vector Machine (SVM), Random Forest (RF), Artificial Neural Network (ANN) and eXtreme Gradient Boosting (XGBoost). We assessed the models' performance and compared the optimal ML model against three existing trauma evaluation scores, including Injury Severity Score (ISS), Trauma Index (TI) and Glasgow Coma Scale (GCS). In addition, we identified several important clinical predictors that made contributions to the prognostic models. The XGBoost-based polytrauma mortality prediction model demonstrated a predictive ability with an accuracy of 90% and an F-score of 88%, outperforming SVM, RF and ANN models. In comparison to conventional scoring systems, the XGBoost model had substantial improvements in predicting the mortality of polytrauma patients. External validation yielded strong stability and generalization with an accuracy of up to 91% and an AUC of 82%. To predict polytrauma complexity, the XGBoost model maintained its performance over other models and scoring systems with good calibration and discrimination abilities. Feature importance analysis highlighted several clinical predictors of polytrauma complexity and mortality, such as Intracranial hematoma (ICH). Leveraging ML algorithms in polytrauma care can enhance the prognostic estimation of polytrauma patients. This approach may have potential value in the management of polytrauma patients.


Subject(s)
Algorithms , Multiple Trauma , Humans , Retrospective Studies , Calibration , Machine Learning , Multiple Trauma/diagnosis
20.
Front Cardiovasc Med ; 11: 1370290, 2024.
Article in English | MEDLINE | ID: mdl-38562185

ABSTRACT

Background: New-onset atrial fibrillation (NOAF) is prognostic in acute myocardial infarction (AMI). The timely identification of high-risk patients is essential for clinicians to improve patient prognosis. Methods: A total of 333 AMI patients were collected who underwent percutaneous coronary intervention (PCI) at Zhejiang Provincial People's Hospital between October 2019 and October 2020. Least absolute shrinkage and selection operator regression (Lasso) and multivariate logistic regression analysis were applied to pick out independent risk factors. Secondly, the variables identified were utilized to establish a predicted model and then internally validated by 10-fold cross-validation. The discrimination, calibration, and clinical usefulness of the prediction model were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test decision curve analyses, and clinical impact curve. Result: Overall, 47 patients (14.1%) developed NOAF. Four variables, including left atrial dimension, body mass index (BMI), CHA2DS2-VASc score, and prognostic nutritional index, were selected to construct a nomogram. Its area under the curve is 0.829, and internal validation by 10-fold cross-folding indicated a mean area under the curve is 0.818. The model demonstrated good calibration according to the Hosmer-Lemeshow test (P = 0.199) and the calibration curve. It showed satisfactory clinical practicability in the decision curve analyses and clinical impact curve. Conclusion: This study established a simple and efficient nomogram prediction model to assess the risk of NOAF in patients with AMI who underwent PCI. This model could assist clinicians in promptly identifying high-risk patients and making better clinical decisions based on risk stratification.

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