BRT: An Efficient and Scalable Blockchain-Based Revocation Transparency System for TLS Connections.

Log-based public key infrastructure(PKI) refers to a robust class of CA-attack-resilient PKI that enhance transparency and accountability in the certificate revocation and issuance process by compelling certificate authorities (CAs) to submit revocations to publicly and verifiably accessible logs. However, log-based PKIs suffer from a reliance on centralized and consistent sources of information, rendering them susceptible to split-world attacks, and they regrettably fail to provide adequate incentives for recording or monitoring CA behavior. Blockchain-based PKIs address these limitations by enabling decentralized log audits through automated financial incentives. However, they continue to face challenges in developing a scalable revocation mechanism suited for lightweight clients. In this paper, we introduce BRT, a scalable blockchain-based system for certificate and revocation transparency. It serves to log, audit, and validate the status of certificates within the transport layer security (TLS)/secure sockets layer(SSL) PKI domain. We designed an audit-on-chain framework, coupled with an off-chain storage/computation system, to enhance the efficiency of BRT when operating in a blockchain environment. By implementing a blockchain-based prototype, we demonstrate that BRT achieves storage-efficient log recording with a peak compression rate reaching 8%, cost-effective log updates for large-scale certificates, and near-instantaneous revocation checks for users.

Effects of PC6 acupressure on acute and delayed nausea and vomiting induced by chemotherapy in patients with malignant neoplasm: a meta-analysis.

OBJECTIVE: Evaluating the intervention effect of PC6 acupressure on chemotherapy-induced acute, delayed nausea, and vomiting in malignant tumor patients. METHOD: Eleven databases had been retrieved from January 2010 through January 2022. The published meta-analysis literature was hand-searched, and the language was limited to English and Chinese. The protocol of this meta-analysis was registered with PROSPERO (registration number: CRD42022323693). Two reviewers independently selected relevant eligible articles, extracted data, and evaluated the risk of bias. Meta-analysis was statistically analyzed using software RevMan 5.3. RESULT: Ten randomized controlled trials with 975 patients were included. Only two studies were assessed as high quality; eight studies were evaluated as moderate. Meta-analysis showed that compared with the control group, PC6 acupressure reduced the occurrence number of acute (SMD = -0.39,95CI (-0.73, -0.05) P = 0.02), delayed (SMD = -0.51, 95% CI (-0.96, -0.05) P = 0.03) nausea and acute (SMD = -0.42,95% CI (-0.79, -0.06) P = 0.02), delayed (SMD = -0.37, 95% CI (-0.77, 0.03) P = 0.07) vomiting; it reduced the severity of acute (SMD = -0.34, 95% CI (-0.57, -0.11) P = 0.004), delayed (SMD = -0.79, 95% CI (-1.33, -0.25) P = 0.004) nausea and acute (SMD = -0.51, 95% CI (-0.79, -0.23) P = 0.0004), delayed (SMD = -0.50, 95% CI (-0.84, -0.17) P = 0.003) vomiting, while it did not reduced the experience time on acute and delayed CINV. CONCLUSION: The meta-analysis shows the effectiveness of PC6 acupressure in preventing and treating nausea and vomiting. Large, high-quality, well-designed randomized controlled trials are needed in the future to determine the efficacy of PC6 acupressure on chemotherapy-induced nausea and vomiting.

Gorham-Stout disease affecting the spine with cerebrospinal fluid leakage and Chiari-like tonsillar herniation: a rare case report and review of literature.

BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.

Computed Tomography-Guided Percutaneous T4 Thoracic Sympathetic Radiofrequency Thermocoagulation for Primary Palmar Hyperhidrosis: A Retrospective Observational Trial.

PURPOSE: To evaluate the efficacy, safety, and patient satisfaction of computed tomography (CT)-guided percutaneous T4 thoracic sympathetic radiofrequency thermocoagulation (RFT) for the treatment of primary palmar hyperhidrosis (PPHH). MATERIALS AND METHODS: A total of 158 patients who underwent bilateral thoracic sympathetic RFT at the T4 level were analysed. Hyperhidrosis Severity Scale (HDSS), Dermatologic Quality of Life Index (DLQI), patient satisfaction, and adverse events were evaluated within 12 months after RFT. RESULTS: The mean age of the patients was 25.27 years, and 95 (60.1%) were females. The technical success, defined as planned needle placement and completion of RFT, was 99.4%. After the procedure, 243 hands (77.4%) were completely dry; and 58 hands (18.4%) were partially dry. From before RFT to 12 months after RFT, the proportion of hands with the HDSS grades 3 and 4 from 100% decreased to 31.9%; and that with the DLQI scores D and E from 100% decreased to 4.0% (P < .001). The clinical success rate was 76.6%, and the patient satisfaction rate was 80.8% at 12 months after RFT. During the procedures, there was unilateral local bleeding in two patients (0.6%) and bradycardia in five patients (3.2%); after the procedures, unilateral pneumothorax occurred in 15 patients (4.7%) and closed thoracic drainage was performed in two patients (0.6%); thoracic neuralgia occurred in 24 patients (15.2%). The incidence of compensatory hyperhidrosis (CH) 12 months after RFT was 15.2%. CONCLUSIONS: CT-guided percutaneous T4 thoracic sympathetic RFT is safe, effective, and minimally invasive for the treatment of PPHH. LEVEL OF EVIDENCE: Level 2 observational study with dramatic effect.

Impedance Iterative Learning Backstepping Control for Output-Constrained Multisection Continuum Arms Based on PMA.

BACKGROUND: Pneumatic muscle actuator (PMA) actuated multisection continuum arms are widely applied in various fields with high flexibility and bionic properties. Nonetheless, their kinematic modeling and control strategy proves to be extremely challenging tasks. METHODS: The relationship expression between the deformation parameters and the length of PMA with the geometric method is obtained under the assumption of piecewise constant curvature. Then, the kinematic model is established based on the improved D-H method. Considering the limitation of PMA telescopic length, an impedance iterative learning backstepping control strategy is investigated. For one thing, the impedance control is utilized to ensure that the ideal static balance force is maintained constant in the Cartesian space. For another, the iterative learning backstepping control is applied to guarantee that the desired trajectory of each PMA can be accurately tracked with the output-constrained requirement. Moreover, iterative learning control (ILC) is implemented to dynamically estimate the unknown model parameters and the precondition of zero initial error in ILC is released by the trajectory reconstruction. To further ensure the constraint requirement of the PMA tracking error, a log-type barrier Lyapunov function is employed in the backstepping control, whose convergence is demonstrated by the composite energy function. RESULTS: The tracking error of PMA converges to 0.004 m and does not exceed the time-varying constraint function through cosimulation. CONCLUSION: From the cosimulation results, the superiority and validity of the proposed theory are verified.

Predictive Value of Contrast-Enhanced Ultrasound in Chemical Lumbar Sympathectomy for End-Stage Arteriosclerosis Obliterans of the Lower Extremities.

INTRODUCTION: The therapeutic effect of chemical lumbar sympathectomy (CLS) on ischemic diseases of the lower limbs varies greatly among individuals. The time to peak (TTP) response in contrast-enhanced ultrasound (CEUS) can reflect the perfusion disorder of the calf skeletal muscle and the collateral circulation. In this study we evaluated the predictive value of CEUS in patients treated with CLS for end-stage atherosclerotic occlusive disease of the lower extremity (ASO-LE). METHODS: This was a prospective study that included patients with end-stage ASO-LE and moderate to severe pain who had undergone a CEUS examination and CLS procedure and who were observed for 12 months after surgery. The patients' characteristics and prognostic factors, including lower limb pain score, skin temperature, walking distance, and ulcer and gangrene healing, were recorded. RESULTS: Fifty-eight patients with a mean age of 66.24 (range 58-78) years were included in the study, of whom 42 (71.41%) were men. Following the CLS procedure, the numerical rating scale (NRS)-measured pain decreased significantly, and the skin temperature of the affected limb increased significantly (P < 0.05). The satisfaction rate of lower limb pain relief 1 year after operation was 53.45%. Correlation analysis showed that preoperative TTP response was correlated with the NRS score and skin temperature of the affected limb at 6 months and 12 months post surgery (P < 0.05). The binary logistic regression analysis indicated that a longer preoperative TTP response was associated with a higher risk of poor pain relief after CLS (odds ratio 1.126, 95% confidence interval 1.058-1.205). The receiver operating characteristic curve showed that preoperative TTP response had a certain predictive value on CLS treatment effect, with a sensitivity and specificity of 81.5% and 83.9%, respectively. When the preoperative TTP response was > 77.5, the risk of poor response after CLS increased. CONCLUSIONS: Preoperative TTP response was able to predict the therapeutic effect of CLS to a certain extent, and thus may aid physicians in determining the choice of CLS treatment for patients with ASO-LE. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChicTR1900028424 (principal investigator: Yue Wu; date of registration: 21 December 2019).

The Role of Flagellin B in Vibrio anguillarum-Induced Intestinal Immunity and Functional Domain Identification.

Vibrio anguillarum, an opportunistic pathogen of aquatic animals, moves using a filament comprised of polymerised flagellin proteins. Flagellins are essential virulence factors for V. anguillarum infection. Herein, we investigated the effects of flagellins (flaA, flaB, flaC, flaD and flaE) on cell apoptosis, TLR5 expression, and production of IL-8 and TNF-α. FlaB exhibited the strongest immunostimulation effects. To explore the functions of flaB in infection, we constructed a flaB deletion mutant using a two-step recombination method, and in vitro experiments showed a significant decrease in the expression of TLR5 and inflammatory cytokines compared with wild-type cells. However in the in vivo study, expression of inflammatory cytokines and intestinal mucosal structure showed no significant differences between groups. Additionally, flaB induced a significant increase in TLR5 expression based on microscopy analysis of fluorescently labelled TLR5, indicating interactions between the two proteins, which was confirmed by native PAGE and yeast two-hybrid assay. Molecular simulation of interactions between flaB and TLR5 was performed to identify the residues involved in binding, revealing two binding sites. Then, based on molecular dynamics simulations, we carried out thirteen site-directed mutations occurring at the amino acid sites of Q57, N83, N87, R91, D94, E122, D152, N312, R313, N320, L97, H316, I324 in binding regions of flaB protein by TLR5, respectively. Surface plasmon resonance (SPR) was employed to compare the affinities of flaB mutants for TLR5, and D152, D94, I324, N87, R313, N320 and H316 were found to mediate interactions between flaB and TLR5. Our comprehensive and systematic analysis of V. anguillarum flagellins establishes the groundwork for future design of flagellin-based vaccines.

Scavenger receptor MARCO contributes to macrophage phagocytosis and clearance of tumor cells.

Macrophage receptor with collagenous structure (MARCO) is a member of the class A scavenger receptor family which is expressed on the cell surface of macrophages. It is well known that MARCO avidly binds to unopsonized pathogens, leading to its ingestion by macrophages. However, the role of MARCO in the recognition and phagocytosis of tumor cells by macrophages remains poorly understood. In this study, we used lentiviral technology to knockdown and overexpress MARCO and investigated the ability of macrophages to phagocytose tumor cells. Our results showed that MARCO expression was correlated with the ability of macrophages to carry on phagocytosis. MARCO knockdown led to significant decreases in the number of engulfment pseudopodia of macrophages and inhibition of the phagocytosis of tumor cells. On the other hand, MARCO overexpression elevated activity of SYK, PI3K and Rac1 in macrophages, which led to changes in macrophage morphology and enhanced phagocytosis by promoting formation of stress fibers and pseudopodia. By Co-IP analysis we showed that MARCO directly binds to the ß5 integrin of SL4 tumor cells. In summary, these results demonstrated the important role for MARCO in demonstrated tumor cells uptake and clearance by macrophages.

Molecular identification and functional analysis of MyD88 in giant freshwater prawn (Macrobrachium rosenbergii) and expression changes in response to bacterial challenge.

Myeloid differentiation factor 88 (MyD88) is a crucial adaptor protein for Toll-like receptor (TLR)-mediated signaling pathways and plays an important role in immune response. In this study, the full-length cDNA of MyD88 from Macrobrachium rosenbergii (MRMyD88) was cloned. The MRMyD88 cDNA is 1758 bp long and contains a 1398-bp open reading frame. Multiple sequence alignment and phylogenetic analysis revealed that the amino acid sequence of MRMyD88 shared high identity with the known MyD88 proteins. The MRMyD88 mRNA was widely expressed in all examined tissues, with highest level in intestine, followed by gonad and pleopod. Furthermore, the MRMyD88 promoter region, spanning 1622 bp, contains several transcription factor-binding sites, including nine GATA-1 box motifs. Electrophoretic mobility shift assay showed that Gfi-1, SRF, and Oct-1 bind to the upstream region of MRMyD88. Additionally, the results showed that the expression levels of TLR1, TLR2 and TLR3 were different in response to Vibrio anguillarum, Lactobacillus plantarum and Aeromonas hydrophila infections. However, these bacteria significantly increased the expression levels of MyD88 and prophenoloxidase. These data suggest that the TLR-mediated signaling pathway is MyD88-dependent in response to pathogenic and probiotic bacteria in M. rosenbergii.

Construction of a Vibrio anguillarum flagellin B mutant and analysis of its immuno-stimulation effects on Macrobrachium rosenbergii.

Vibrio anguillarum is a globally distributed aquatic pathogen, and its flagellin B (FlaB) protein can evoke innate immune responses in hosts. In order to explore the role of FlaB in V. anguillarum infection, we constructed a FlaB-deficient mutant using overlapping PCR and two-step homologous recombination, and gene sequencing confirmed successful knockout of the FlaB gene. Scanning electron microscopy showed no significant differences in the morphological structure of the flagellum between wild-type and FlaB-deficient strains. The mutant was subsequently injected into the freshwater prawn (Macrobrachium rosenbergii) to explore its pathogenicity in the host, and expression of myeloid differentiation factor 88, prophenoloxidase, catalase, superoxide dismutase and glutathione peroxidase was investigated by real-time PCR. The results showed that deletion of FlaB had little effect on V. anguillarum-induced expression of these immune-related genes (p > 0.05). In general, the FlaB mutant displayed similar flagella morphology and immune characteristics to the wild-type strain, hence we speculated that knockout of FlaB might promote the expression and function of other flagellin proteins. Furthermore, this study provides a rapid and simple method for obtaining stable mutants of V. anguillarum free from foreign plasmid DNA.

Effect of traditional Chinese medicine (TCM) on survival, quality of life, and immune function in patients with ovarian carcinoma: A protocol for systematic review and meta analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has been widely applied as promising adjunctive drugs for ovarian carcinoma (OC) in China and other Asian countries. However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of TCM on survival, quality of life (QoL), and immune function in patients with OC through the meta-analysis. METHODS: Relevant clinical trials of TCM for the treatment OC patients will be searched in Cochrane Library, Web of Science, Google Scholar, PubMed, Medline, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database from their inception to November 2020. Two researchers will perform data extraction and risk of bias assessment independently. The clinical outcomes, including overall survival (OS), QoL, immune function, tumor markers, and adverse events, were systematically evaluated by using Review Manager 5.3 and Stata 14.0 statistical software. RESULTS: The results of this study will provide high-quality evidence for the effect of TCM on survival, QoL and immune function in patients with OC. CONCLUSION: The conclusions of this meta-analysis will be published in a peer-reviewed journal, and draw an objective conclusion of the efficacy of TCM on survival, QoL, and immune function in patients with OC. TRIAL REGISTRATION NUMBER: INPLASY2020110104.

Effects of heat treatment, homogenization pressure, and overprocessing on the content of furfural compounds in liquid milk.

BACKGROUND: Sterilization of milk is aimed at killing the microorganisms present. There are three main sterilization methods commonly used in milk processing: high temperature and short time (HTST) pasteurization, ultrahigh pasteurization (UP), and ultrahigh temperature (UHT) sterilization. The Maillard reaction is of special interest in studying the effect of heat treatment on milk quality. Furfural compounds are one of the typical intermediates of the Maillard reaction, which have safety risks related to mutagenic and genotoxic effects. The furfural compounds content is directly related to the heat treatment intensity. RESULTS: The furfural compounds content was measured using high-performance liquid chromatography with ultraviolet detection in 12 min. Then, 13 levels of heat treatment intensity (combinations of temperature and time) and three levels of homogenization pressure were selected to study the change of the furfural compounds content after different processing technologies in a pilot plant. The results show a higher temperature treatment can stimulate more Maillard reaction intermediates, such as hydroxymethylfurfural and furfural. A temperature regression evaluation model and content prediction models of hydroxymethylfurfural and furfural were developed to quantify the relationship between the furfural content and heat treatment with the data from the pilot plant. CONCLUSION: Based on the temperature evaluation model, the heating temperature of three milk products was evaluated. The homogenization pressures had little effect on the furfural content in liquid milk. The emergence of the furyl methyl ketone and methylfurfural can be detected after overprocessing of the liquid milk. © 2020 Society of Chemical Industry.

Unbounded and revocable hierarchical identity-based encryption with adaptive security, decryption key exposure resistant, and short public parameters.

Revocation functionality and hierarchy key delegation are two necessary and crucial requirements to identity-based cryptosystems. Revocable hierarchical identity-based encryption (RHIBE) has attracted a lot of attention in recent years, many RHIBE schemes have been proposed but shown to be either insecure or bounded where they have to fix the maximum hierarchical depth of RHIBE at setup. In this paper, we propose a new unbounded RHIBE scheme with decryption key exposure resilience and with short public system parameters, and prove our RHIBE scheme to be adaptively secure. Our system model is scalable inherently to accommodate more levels of user adaptively with no adding workload or restarting the system. By carefully designing the hybrid games, we overcome the subtle obstacle in applying the dual system encryption methodology for the unbounded and revocable HIBE. To the best of our knowledge, this is the first construction of adaptively secure unbounded RHIBE scheme.

[Preparation of triterpene saponins from Platycodon grandiflorum by two-dimensional hydrophilic interaction liquid chromatography-reversed phase liquid chromatography].

A two-dimensional (2-D) preparative liquid chromatography method was developed for the preparation of triterpene saponins from Platycodon grandiflorum using hydrophilic interaction liquid chromatography (HILIC) coupled with reversed phase liquid chromatography (RPLC). At first, the crude extract was obtained from Platycodon grandiflorum by boiled alcohol precipitation. Then, the concentrated crude extracts were continuously pretreated using solid phase extraction (SPE) under reversed-phase and hydrophilic-phase modes to remove the impurities. Subsequently, XAmide column (150 mm x 20 mm, 5 microm) was selected to separate the triterpene saponin constituents under HILIC mode using water and acetonitrile as mobile phases. From 6 min to 25 min, each fraction was collected per minute under time-triggered mode and 20 fractions were collected. The 18th fraction (JG23) was selected for further purification. The column of Atlantis PrepT3 (100 mm x 30 mm, 5 microm) was chosen and two monomeric compounds were obtained. The two compounds with over 90% purity were identified as deapiplatycoside E and platycoside E with mass spectrometry (MS) and nuclear magnetic resonance (NMR). This 2-D HILIC-RPLC method with high orthogonality can be used in the preparation of triterpene saponins from natural products.

Comprehensive HILIC × RPLC with mass spectrometry detection for the analysis of saponins in Panax notoginseng.

A comprehensive off-line two-dimensional liquid chromatography (2D-LC) method coupling hydrophilic interaction liquid chromatography (HILIC) and reversed phase liquid chromatography (RPLC) was developed in this study to detect as many saponins as possible in extracts of Panax notoginseng. The orthogonality of the 2D HILIC × RPLC was up to 81%, and the peak capacity was 10200. In total, 224 saponins were found, and some of them were trace amounts. Besides, a screening table designed by adding molecular weights of possible aglycones and sugars was constructed to help rapidly characterize the saponins using MS information. Unfortunately, the structure of saponins could not be identified by using only MS information.