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Abstract Spinal manipulative therapy (SMT) has been shown to significantly alleviate pain in patients with lumbar disc herniation (LDH), with its effects closely associated with brain function modulation. This study investigates the neural biomarkers linked to pain relief efficacy following a complete SMT treatment cycle in LDH patients. A total of 59 LDH patients were randomized into two groups: SMT treatment (Group 1, n = 28) and sham treatment (ST) (Group 2, n = 31). A matched healthy control group (Group 3, n = 28) was also included. Functional magnetic resonance imaging (fMRI) was performed on LDH patients at two time points (TPs)—before (TP1) and after (TP2) treatment—while healthy controls were scanned once. Clinical assessments were conducted using the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) scale. Post-treatment results indicated significant improvements in both VAS and JOA scores for Group 1, while the improvement was limited to VAS scores for Group 2. Graph properties analysis revealed notable differences in brain network connectivity between LDH patients and healthy controls, particularly between the left precentral gyrus (left PreCG) and left inferior frontal gyrus, opercular part (left IFGoperc). Enhanced functional connectivity (FC) was observed in Group 1, notably between the right angular gyrus (right ANG) and the left middle orbital gyrus (left ORBmid), with right ANG showing a significant positive correlation with clinical scores. This study identifies the sensorimotor network—salience network are significantly activated in chronic pain among LDH patients. The default mode network—dorsal attention network may serve as key neural biomarkers for the efficacy of SMT treatment in alleviating pain in LDH.

Abstract Streptococcus pneumoniae is a significant pathogen causing infectious diseases, including pneumonia, otitis media, septicemia, and meningitis. The introduction of multivalent vaccines has coincided with a remarkable decrease in the number of pneumococcal-related deaths. Despite this, pneumococcal infection remains a significant cause of death among children under 5 years old and adults aged 65 or older at a global level. Therefore, early detection of S. pneumoniae infection is crucial for prognosis of pneumococcal infection patients. In this study, we evaluated the utility of a real-time multienzyme isothermal rapid amplification (MIRA) assay for detecting S. pneumoniae and other non-S. pneumoniae bacterial species. A primer–probe set targeting the S. pneumoniae lytA gene was designed, followed by optimization of parameters for the MIRA assay. At the same time, we validated the real-time MIRA assay for detecting S. pneumoniae using 79 clinical isolates identified by VITEK MS. The results showed a detection sensitivity and specificity of 100%. These results demonstrate that the designed real-time MIRA assay is a promising, rapid, simple, and reliable method for detecting S. pneumoniae infection in resource-limited areas. It has great potential for application in detecting not only S. pneumoniae but also other non-S. pneumoniae bacterial species.

Background Inflammation and metabolic disturbances are key culprits in the pathogenesis of obesity‐associated cardiomyopathy. The NLRP3 (nucleotide‐binding oligomerization domain‐like receptor 3) inflammasome mediates the release of the proinflammatory cytokines IL‐1β (interleukin‐1β) and IL‐18 by activating caspase‐1, which is strongly implicated in metabolic disturbances. We here sought to determine whether NLRP3 inflammasome inhibition could ameliorate obesity cardiomyopathy and if so, to further explore its underlying mechanisms. Methods and Results Male mice were fed a high‐fat diet for 24 weeks to induce obesity cardiomyopathy. MCC950 was used to inhibit NLRP3 inflammasome activation. Recombinant adeno‐associated virus serotype 9 encoding TXNIP (thioredoxin‐interacting protein) under cTnT (cardiac troponin T) promoter and the mitochondrial‐targeted antioxidant MitoTEMPO were injected into obese mice to investigate the specific mechanism. To mimic obesity cardiomyopathy in vitro, neonatal rat ventricular myocytes transfected with the small interfering RNA against TXNIP were incubated with 400 μmol palmitic acid for 24 hours. NLRP3 inflammasome was significantly increased in obese hearts. NLRP3 inflammasome inhibition by NLRP3 deletion or MCC950 prevented obesity‐induced cardiac systolic and diastolic dysfunction, myocardial hypertrophy and fibrosis, and excessive lipid accumulation in male mice. Conversely, TXNIP overexpression worsened obesity‐associated cardiomyopathy. Similarly, MCC950 treatment or TXNIP knockdown reduced palmitic acid‐induced NLRP3 inflammasome activation and lipid storage. Mechanistically, abnormal NF‐κB (nuclear factor kappa B) pathway activation, increased mitochondrial reactive oxygen species, and elevated TXNIP levels led to excessive NLRP3 inflammasome activation. Conclusions Our study confirms that aberrant NLRP3 inflammasome activation in cardiomyocytes worsens obesity‐associated cardiomyopathy and implicates inhibition of NLRP3 inflammasome as a potent therapeutic approach for obesity cardiomyopathy.

Background Type A aortic dissection presents challenges with postoperative cerebral complications, and this study evaluates the predictive value of quantitative electroencephalography for perioperative brain function prognosis. Methods and Results Amplitude‐integrated electroencephalography (aEEG) processes raw signals through filtering, amplitude integration, and time compression, displaying the data in a semilogarithmic format. Using this method, postoperative relative band power (post‐RBP) α% and dynamic aEEG (ΔaEEG) grade were significantly associated with neurological dysfunction in univariate and multivariable analyses, with area under the receiver operating characteristic curve of 0.876 (95% CI, 0.825–0.926) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with adverse outcomes, with area under the receiver operating characteristic curve of 0.903 (95% CI, 0.835–0.971) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with transient neurological dysfunction and stroke, with areas under the receiver operating characteristic curve of 0.818 (95% CI, 0.760–0.876) and 0.868 (95% CI, 0.810–0.926) for transient neurological dysfunction, and 0.815 (95% CI, 0.743–0.886) and 0.831 (95% CI, 0.746–0.916) for stroke. Among 56 patients, the Alberta Stroke Program Early Computed Tomography score was superior to ΔaEEG in predicting neurological outcomes (area under the receiver operating characteristic curve of 0.872 versus 0.708 [95% CI, 0.633–0.783]; P

Abstract Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002–1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250–5.475), hemopericardium (OR, 2.767; 95% CI, 1.150–7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001–1.014), RBP Delta (OR, 1.047; 95% CI, 1.020–1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794–0.907), and Beta (OR, 0.755; 95% CI, 0.649–0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011–1.032), RBP Delta (OR, 1.168; 95% CI, 1.105–1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135–1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p

Abstract Background Acute Type A aortic dissection (ATAAD) is a life-threatening cardiovascular disease associated with high mortality rates, where surgical intervention remains the primary life-saving treatment. However, the mortality rate for ATAAD operations continues to be alarmingly high. To address this critical issue, our study aimed to assess the correlation between preoperative laboratory examination, clinical imaging data, and postoperative mortality in ATAAD patients. Additionally, we sought to establish a reliable prediction model for evaluating the risk of postoperative death. Methods In this study, a total of 384 patients with acute type A aortic dissection (ATAAD) who were admitted to the emergency department for surgical treatment were included. Based on preoperative laboratory examination and clinical imaging data of ATAAD patients, logistic analysis was used to obtain independent risk factors for postoperative in-hospital death. The survival prediction model was based on cox regression analysis and displayed as a nomogram. Results Logistic analysis identified several independent risk factors for postoperative in-hospital death, including Marfan syndrome, previous cardiac surgery history, previous renal dialysis history, direct bilirubin, serum phosphorus, D-dimer, white blood cell, multiple aortic ruptures and age. A survival prediction model based on cox regression analysis was established and presented as a nomogram. The model exhibited good discrimination and significantly improved the prediction of death risk in ATAAD patients. Conclusions In this study, we developed a novel survival prediction model for acute type A aortic dissection based on preoperative clinical features. The model demonstrated good discriminatory power and improved accuracy in predicting the risk of death in ATAAD patients undergoing open surgery.

Abstract Background Postoperative hyper-inflammation is a frequent event in patients with acute Stanford type A aortic dissection (ATAAD) after surgical repair. This study's objective was to determine which inflammatory biomarkers could be used to make a better formula for identifying postoperative hyper-inflammation, and which risk factors were associated with hyper-inflammation. Methods A total of 405 patients were enrolled in this study from October 1, 2020 to April 1, 2023. Of these patients, 124 exhibited poor outcomes. In order to investigate the optimal cut-off values for poor outcomes, logistic and receiver operating characteristic analyses were performed on the following parameters on the first postoperative day: procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and systemic immune-inflammation index (SII). These cut-off points were used to separate the patients into hyper-inflammatory (n = 52) and control (n = 353) groups. Finally, the logistic were used to find the risk factors of hyper-inflammatory. Results PCT, CRP, IL-6, and SII were independent risk factors of poor outcomes in the multivariate logistic model. Cut-off points of these biomarkers were 2.18 ng/ml, 49.76 mg/L, 301.88 pg/ml, 2509.96 × 109/L respectively. These points were used to define postoperative hyper-inflammation (OR 2.97, 95% CI 1.35–6.53, P 180 min, and deep hypothermia circulatory arrest (DHCA) > 40 min were the independent risk factors for hyper-inflammation. Conclusions PCT > 2.18, CRP > 49.76, IL-6 > 301.88, and SII 180 min and DHCA > 40 min were separate risk factors for postoperative hyper-inflammation.

Abstract Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross‐presentation, the progress with neoantigen peptide‐based vaccines has obviously lagged in clinical trials. Here, a stapling peptide‐based nano‐vaccine is developed, comprising a self‐assembly nanoparticle driven by the nucleic acid adjuvant‐antigen conjugate. This nano‐vaccine stimulates a strong tumor‐specific T cell response by activating antigen presentation and toll‐like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co‐delivery to the draining lymph nodes, the nano‐vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long‐term anti‐tumor memory. Moreover, the injection of nano‐vaccine with signal neoantigen eliminates the established MC‐38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide‐based nano‐vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti‐tumor immune response for the neoantigen peptide‐based personalized tumor immunotherapy.

Abstract T-box riboswitches are multi-domain noncoding RNAs that surveil individual amino acid availabilities in most Gram-positive bacteria. T-boxes directly bind specific tRNAs, query their aminoacylation status to detect starvation, and feedback control the transcription or translation of downstream amino-acid metabolic genes. Most T-boxes rapidly recruit their cognate tRNA ligands through an intricate three-way stem I-stem II-tRNA interaction, whose establishment is not understood. Using single-molecule FRET, SAXS, and time-resolved fluorescence, we find that the free T-box RNA assumes a broad distribution of open, semi-open, and closed conformations that only slowly interconvert. tRNA directly binds all three conformers with distinct kinetics, triggers nearly instantaneous collapses of the open conformations, and returns the T-box RNA to their pre-binding conformations upon dissociation. This scissors-like dynamic behavior is enabled by a hinge-like pseudoknot domain which poises the T-box for rapid tRNA-induced domain closure. This study reveals tRNA-chaperoned folding of flexible, multi-domain mRNAs through a Venus flytrap-like mechanism.

Abstract Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in imaging technologies have shed light on how the centrosome is organized, how its constituent proteins are coherently architected to elicit downstream events remains poorly understood. Using multidisciplinary approaches, we showed that two long coiled-coil proteins, Cep63 and Cep152, form a heterotetrameric building block that undergoes a stepwise formation into higher molecular weight complexes, ultimately generating a cylindrical architecture around a centriole. Mutants defective in Cep63•Cep152 heterotetramer formation displayed crippled pericentriolar Cep152 organization, polo-like kinase 4 (Plk4) relocalization to the procentriole assembly site, and Plk4-mediated centriole duplication. Given that the organization of pericentriolar materials (PCM) is evolutionarily conserved, this work could serve as a model for investigating the structure and function of PCM in other species, while offering a new direction in probing the organizational defects of PCM-related human diseases.

Although e-voting scheme and e-cheque scheme are two different applications, they have similarities in the scheme definitions and security properties. This inspires us to establish a relationship between the two schemes by formalising a generic transformation from e-voting to e-cheque scheme. Firstly, we define the scheme definitions and security models for both e-voting scheme and e-cheque scheme. Subsequently, we demonstrate a generic transformation framework from e-voting to e-cheque with asymptotic complexity of [Formula: see text] and design a formal proof to show that a secure e-voting scheme can be transformed into a secure e-cheque scheme. As a proof of concept, we apply our newly proposed transformation technique to the e-voting scheme proposed by Li et al. and obtain a concrete e-cheque scheme.

RNA conformational heterogeneity is important to diverse functions. Here, the authors use AFM to directly visualize individual RNA molecules that are in various conformational states under near physiological solution conditions for the first time.