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Dentin hypersensitivity (DH) manifests as sharp and uncomfortable pain due to the exposure of dentinal tubules (DTs) following the erosion of tooth enamel. Desensitizing agents commonly used in clinical practice have limitations such as limited depth of penetration, slow remineralization and no antimicrobial properties. To alleviate these challenges, our study designed a lactoferrin-derived amyloid nanofilm (PTLF nanofilm) inspired by the saliva-acquired membrane (SAP). The nanofilm utilises Tris(2-carboxyethyl)phosphine (TCEP) to disrupt the disulfide bonds of lactoferrin (LF) under physiological conditions. The PTLF nanofilm modifies surfaces across various substrates and effectively prevents the early and stable adhesion of cariogenic bacteria, such as Streptococcus mutans and Lactobacillus acidophilus. Simultaneously, it adheres rapidly and securely to demineralized dentin surfaces, facilitating in-situ remineralization of HAP through a simple immersion process. This leads to the formation of a remineralized layer resembling natural dentin, with an occlusion depth of dentinal tubules exceeding 80 µm after three days. The in vivo and vitro results confirm that the PTLF nanofilm possesses good biocompatibility and its ability to exert simultaneous antimicrobial effects and dentin remineralization. Accordingly, this innovative bifunctional PTLF amyloid coating offers promising prospects for the management of DH-related conditions. 1. We design a simple, fast, inexpensive, and easy-to-process PTLF nanofilm for nearly any material surface or shape. 2. The PTLF nanofilm modifies surfaces across various substrates and effectively prevents the adhesion of cariogenic bacteria, such as Streptococcus mutans and Lactobacillus acidophilus. 3. The abundant functional groups on the surface of PTLF nanofilm facilitate bioactive hydroxyapatite (HAP) formation and maintain stability at the HAP remineralization interface. [Display omitted] [ABSTRACT FROM AUTHOR]

Forward Freight Agreements (FFAs) are consequential derivatives for risk hedging in the shipping market. This paper presents the first empirical study of convenience yield in the shipping market with a sample of C3 (Tubarao to Qingdao) and C5 (Western Australia to Qingdao) FFAs from 2013 to 2023. First, single-factor and two-factor models are constructed to analyze the random behavior of freight rates in the shipping market, and the existence of convenience yield is empirically tested. The results provide evidence of the existence of convenience yield in the shipping market, with its stochastic variation being a critical factor in shaping the term structure characteristics of FFAs. Second, an ARMAX model is developed for the freight rate index, and the predictive role of the estimated convenience yield and its difference in spot freight rates is analyzed by operating the two-factor model. The findings reveal a significant predictive effect of convenience yield and its difference on spot freight rates. Last but not least, this study emphasizes the importance of convenience yield as a crucial parameter in the shipping market, particularly regarding the transportation of bulk commodities. Changes in the supply and demand of bulk commodities directly impact the fluctuations in shipping market capacity and convenience yield. This study delivers a new explanatory perspective for price formation in the shipping market and is highly valuable for risk management in this sector. [ABSTRACT FROM AUTHOR]

Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14–3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29–5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41–7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86–8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05–2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79–4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862–0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection. [ABSTRACT FROM AUTHOR]

Microneedle patches (MNs) have demonstrated potentials in transdermal drug delivery for skin disease therapy. Effort is mainly focused on the improvement of MNs' materials, structures and functions to realize intelligent drug delivery. Here, we propose a novel black phosphorus (BP)-loaded hydrogel inverse opal MNs with photothermal responsive capacity and vivid structural color screening for psoriasis treatment. The MNs, composed of a BP-loaded N-isopropyl acrylamide (NIPAM)/poly(ethylene glycol) diacrylate (PEGDA) inverse opal hydrogel scaffold and the drug-carrying gelatin/agarose filler inside the scaffold pores, are fabricated through combined approaches of nanoparticle assembly, reversed-phase replication and micro-molding. Due to the photothermal conversion of BP, temperature-responsive shrinkage of NIPAM, and heat-sensitive gelatin, the resulting MNs obtain the ability of good hydrophobic drug loading and photothermal controllable drug release. In addition, profiting from the inverse opal structure with optical properties, the MNs exhibit a bright structural color and can generate characteristic wavelength shift during drug release, providing a real-time monitoring and feedback for drug delivery. Based on these features, the MNs show excellent in vivo drug administration and efficient psoriasis treatment in mice, indicating their potential as intelligent drug delivery vehicles for practical applications. [Display omitted] • Microneedle patches (MNs) have demonstrated potentials in transdermal drug delivery for skin disease therapy. • A novel black phosphorus (BP)-loaded hydrogel inverse opal MNs with photothermal responsive capacity and vivid structural color screening was proposed for psoriasis treatment. • Due to the photothermal conversion of BP, temperature-responsive shrinkage of NIPAM, and heat-sensitive gelatin, the resulting MNs obtain the ability of good hydrophobic drug loading and photothermal controllable drug release. • Profiting from the inverse opal structure with optical properties, the MNs exhibit a bright structural color and can generate characteristic wavelength shift during drug release, providing a real-time monitoring and feedback for drug delivery. • The MNs show excellent in vivo drug administration and efficient psoriasis treatment in mice, indicating their potential as intelligent drug delivery vehicles for practical applications. [ABSTRACT FROM AUTHOR]

Abstract Rolling element bearings are key and also vulnerable machine elements in rotating machinery. Fault diagnosis of rolling element bearings is significant for guaranteeing machinery safety and functionality. To accurately extract bearing diagnostic information, a time–frequency analysis method based on continuous wavelet transform (CWT) and multiple Q-factor Gabor wavelets (MQGWs) (termed CMQGWT) is introduced in this paper. In the CMQGWT method, Gabor wavelets with multiple Q-factors are adopted and sets of the continuous wavelet coefficients for each Q-factor are combined to generate time–frequency map. By this way, the resolution of the CWT time–frequency map can be greatly increased and the diagnostic information can be accurately identified. Numerical simulation is carried out and verified the effectiveness of the proposed method. Case studies and comparisons with the continuous Morlet wavelet transform (CMWT) and the tunable Q-factor wavelet transform (TQWT) demonstrate the effectiveness and superiority of the CMQGWT for bearing diagnostic information extraction and fault identification. Highlights • A time–frequency analysis method termed CMQGWT is proposed for bearing fault diagnosis. • Gabor wavelets with multiple Q-factors are introduced and used in the proposed method. • Numerical simulation shows the method provides a time–frequency map with super resolution. • Cases demonstrate the advantages of the method for bearing diagnostic information extraction. [ABSTRACT FROM AUTHOR]

Abstract Machinery vibration signal is a typical multi-component signal and fault features are often submerged by some interference components. To accurately extract fault features, a weak feature enhancement method based on empirical wavelet transform (EWT) and an improved adaptive bistable stochastic resonance (IABSR) is proposed. This method makes full use of the signal decomposition performance of EWT and the signal enhancement of the IABSR to achieve the purpose of fault feature enhancement in low frequency band of FFT spectrum. Firstly, EWT is used as the preprocessing program of bistable stochastic resonance (BSR) to decompose the machinery vibration signal into a set of sub-components. Then, the sensitive component that contains main fault information is further input into BSR system to enhance fault features with the assistance of residual noises. Finally, the fault features are identified from fast Fourier transform (FFT) spectrum of the BSR output. To achieve the optimal BSR output, the IABSR method based on salp swarm algorithm (SSA) is presented. Compared with the tradition adaptive BSR (ABSR), the IABSR optimizes not only the BSR system parameters but also the calculation step size. Two case studies on machinery fault diagnosis demonstrate the effectiveness and superiority of the proposed method. In addition, the proposed method is easy to implement and is robust to noise to some extent. Highlights • A fault feature enhancement method based on EWT and an IABSR is proposed. • EWT is used as the preprocessing program to decompose the signal into a set of sub-components. • The IABSR method is developed to enhance fault feature information. • Numerical simulation validates the effectiveness and advantages of the IABSR method. • Case studies on machinery fault diagnosis demonstrate superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Background & Aims Endoscopic ultrasound (EUS)-guided fine needles with side fenestrations are used to collect aspirates for cytology analysis and biopsy samples for histologic analysis. We conducted a large, multicenter study to compare the accuracy of diagnosis via specimens collected with fine-needle biopsy (FNB) versus fine-needle aspiration (FNA) for patients with pancreatic and nonpancreatic masses. Methods We performed a prospective single-blind study at 5 tertiary care centers in China. The study comprised 408 patients undergoing EUS for a solid mass (>1 cm) in the pancreas, abdomen, mediastinum, or pelvic cavity, from December 2014 through January 2016. Patients were randomly assigned to groups (1:1) for assessment by FNA (n = 190) or FNB (n = 187). After lesions were identified by EUS, samples were collected in a total of 4 passes by each needle. All procedures were performed by experienced endosonographers; cytologists and pathologists were blinded to the sample collection method. Patients were followed for at least 48 weeks, and final diagnoses were obtained after surgery, imaging analysis, or resolution of lesion. The primary aim was to compare diagnostic yields of EUS-FNA with EUS-FNB for all solid masses, then separately as pancreatic and nonpancreatic masses. The secondary endpoint was the quality of histologic specimen. Results Findings from FNB analysis were accurate for 91.44% of all cases, compared with 80.00% for all FNA cases, based on final patient diagnoses ( P = .0015). In patients with pancreatic masses (n = 249), findings from histologic analysis of FNBs were accurate for 92.68% of the cases, compared with 81.75% for FNAs ( P = .0099). In cytology analysis of pancreatic masses, samples collected by FNB accurately identified 88.62% of all pancreatic lesions, whereas samples collected by FNA accurately identified 79.37% ( P = .00468). Analyses of samples of nonpancreatic masses collected by FNA versus FNB produced similar diagnostic yields. Conclusions In a prospective study of patients with pancreatic masses, we found EUS-guided FNB samples to produce more accurate diagnoses than samples collected by EUS-guided FNA samples. No difference in diagnostic yield was seen between EUS-FNA and EUS-FNB for nonpancreatic masses. Clinical Trials.gov no: NCT02327065 . [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the direct antitumor activity of edible fungal polysaccharide Lentinan, rather than as a host defence potentiator, on human breast cancer and investigate its underlying mechanisms. The present results revealed that there were 45.46% and 59.16% of inhibitory rate after Lentinan treatment in MCF-7 cells and tumor-bearing athymic nude mice, respectively. Annexin V-FITC/PI, H&E staining and TUNEL assay showed that Lentinan induced cell apoptosis which accompanied with abundant activated caspase-7, increased cytosol cytochrome c and Bax/Bcl-2. Unexpectedly, we firstly demonstrated that Lentinan could stimulate cell autophagy according to the detection of autophagosomes and autophagic flux. Pretreatment with autophagy inhibitors decreased Lentinan-induced cells death. These findings provided new insight into the mechanisms of Lentinan-antitumor effect and contributed to its development in functional foods and cancer therapy. [ABSTRACT FROM AUTHOR]

MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc +/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. " Myc KO" mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, Myc KO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in Myc KO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc. [Display omitted] • Postnatal body-wide deletion of the Myc gene in mice causes premature aging • " Myc KO" mice dysregulate numerous genes involved in aging, senescence, and cancer • Myc KO mice live longer and have a low lifetime cancer incidence • Normal aging in mice and humans is associated with Myc downregulation Wang et al. show that the postnatal elimination of Myc causes premature aging and the deterioration of age-sensitive functions. Yet, these mice have extended lifespans and a reduced cancer incidence. Gradual Myc downregulation accompanies normal aging in many tissues. Thus, the strong relationship between aging and cancer can be severed by eliminating a single gene. [ABSTRACT FROM AUTHOR]

Microneedles-based tumor therapy has obtained much focus in both biomedical research and clinical applications, while their efficient and synergetic strategy with minimal adverse effects remains highly expected. Herein, we develop a novel photosensitizer-immunotherapy integrated microneedles (MNs) with the required functions to prevent breast cancer recurrence and metastasis after surgery. Utilizing the enhanced penetration capability of MNs, the nanophotosensitizers with significant photodynamic and photothermal effects can be precisely targeted delivered and aggregated in the deep residual tumor tissue. Besides, with the hyperthermia of infrared ray (NIR) irradiation, the penetrated MNs can melt to release intrinsic photosensitizer in situ, achieving controllable drug release. As the reactive oxygen species and local hyperthermia generated from NIR-triggered nanophotosensitizers can induce the immunogenic death of residual cancer cells and evoke DCs maturation for system immunity, the proposed MNs can effectively protect against local tumor relapse and distant metastasis synergy with immune checkpoint inhibitors in the murine model. Thus, we believe that the photosensitizer-immunotherapy integrated MNs hold great potential for clinical translation. [Display omitted] • Phototherapy has shown encouraging potential but is hampered by the photosensors' insufficient delivery. • A novel dissolvable microneedle patch is fabricated to deliver nano-photosensitizers for preventing tumor recurrence. • The proposed MNs can effectively protect against tumor relapse and metastasis synergy with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins are the most potent protein neurotoxin known to human. The dual roles of BoNTs as both the causative agent of human botulism and a widely used protein-based therapeutic agent for treatment of numerous neuromuscular disorders/cosmetic uses make it an extremely hot topic of research. Biochemical characterization of these toxins was mainly confined to the recombinant light chains and substrate and little is known about their efficiency on the cleavage of endogenous substrates. In the present study, we showed that BoNTs exhibited variable activities on their endogenous substrates and that their efficiency to cleave recombinant and endogenous substrate was not consistent, presumably due to the differential recognition of their respective substrates in the natural SNARE complex format. Through testing the combinatorial effects of different BoNTs on cleavage of endogenous substrates, we showed that the combinations of LC/A and LC/B, as well as LC/A and LC/F, could enhance the activity of each individual BoNT. This finding may shed light on the future development of new BoNT serotypes for clinical application, and formulation of combinatorial uses of different BoNTs to minimize the development of immuno-resistance by using a lower amount of individual type. [ABSTRACT FROM AUTHOR]

JLNT, a purified polysaccharide with the structure of β-(1→3)-D-glucose main chains and β-(1→6)-D-glucose side chains and with an average molecular weight of 605.4 kDa, was extracted and isolated from the fruitbodies of Lentinus edodes, which has immunoregulatory activity and anti-tumour effects. In the present study, we found that JLNT possessed direct anti-tumour effects on MCF-7 and S180 cells and apoptosis -inducing activity in S180 tumour bearing mice. Therefore, we investigated the mechanisms of JLNT-induced apoptosis. Results showed that JLNT increased the expression of p53, enhanced the Bax/Bcl-2 ratios by up-regulating Bax and down-regulating Bcl-2, promoted the expression of Smac, leading to the activation of caspase-3 and finally the initiation of cell apoptosis in S180 tumour bearing mice. Taken together, these findings provide the experimental evidence that JLNT could induce apoptosis of S180 cells via mitochondria pathways. [ABSTRACT FROM AUTHOR]

Hematophagous arthropods, such as mosquitoes, naturally carry and transmit hundreds of arboviruses to humans. Blood meal is a predominant physical interface that shapes cross-species communications among humans, bloodsuckers, and arboviruses. Here, we identify a human-blood-derived microRNA, hsa-miR-150-5p, that interferes with a mosquito antiviral system to facilitate flavivirus infection and transmission. hsa-miR-150-5p is acquired with a blood meal into the mosquito hemocoel and persists for a prolonged time there. The agomir of hsa-miR-150-5p enhances, whereas the antagomir represses flaviviral infection in mosquitoes and transmission from mice to mosquitoes. Mechanistic studies indicate that hsa-miR-150-5p hijacks the mosquito Argonaute-1-mediated RNA interference system to suppress the expression of some chymotrypsins with potent virucidal activity. Mosquito chymotrypsins are essential for resisting systemic flavivirus infection in hemocoel tissues. Chymotrypsin homologs potentially targeted by miR-150-5p are also found in other hematophagous arthropods, demonstrating a conserved miR-150-5p-mediated cross-species RNAi mechanism that might determine flaviviral transmissibility in nature. [Display omitted] • hsa-miR-150-5p is acquired with a blood meal and persists in the mosquito hemocoel • hsa-miR-150-5p facilitates DENV infection in mosquitoes in a cross-species manner • hsa-miR-150-5p suppresses expression of antiviral chymotrypsin genes in mosquitoes • Regulatory role of miR-150-5p is functionally conserved among arthropod vectors Zhu et al. identify a human-blood-derived miRNA, hsa-miR-150-5p, that interferes with a mosquito antiviral system to facilitate flavivirus infection. hsa-miR-150-5p is acquired with a blood meal and persists in the mosquito hemocoel. This study indicates that hsa-miR-150-5p-mediated cross-species RNAi mechanism determines flaviviral transmissibility in nature. [ABSTRACT FROM AUTHOR]

Abstract: Based upon botulinum neurotoxins’ (BoNT) mechanism of action, a novel, rapid, and sensitive avian eyelid assay was developed to detect Clostridium botulinum neurotoxin serotypes A, B and E in assay buffer and mimic samples. It showed that chick was the most optimal model of 20-selected laboratory, non-laboratory animals. The eyelid closure of chick was the indicator symptom for positive results. The detection limits achieved range from 5 to 250 mouse LD50 for toxin types A, B, and E in a buffer system and mimic samples. No cross reactivity occurred when using staphylococcal enterotoxin B, diphtheria toxin and nerve agent sarin, but cross reactivity was obtained in more than 6h for using high dose of tetanus toxin. This cross reactivity can be differentiated by BoNT neutralization tests with a serotype-specific antiserum in parallel. The avian eyelid assay can be performed within as short a time as 0.4–6h. We report here the development of avian eyelid assay is the second animal bioassay for the detection of toxin types A, B, and E which approaches the sensitivity of the mouse bioassay, and is simple to perform as well as rapid to yield results. [Copyright &y& Elsevier]

• A novel ensemble algorithm is proposed to solve the problem of diagnosis under different conditions. • DCELM with fast training speed is used as base learner to extract features from time-frequency images. • The algorithm can select base learners which are negatively correlated in terms of their outputs. • By exploiting unlabeled target domain data, our ensemble achieves "cross-condition" capability. • The effectiveness of the algorithm is evaluated by experiments on gears, rotor and rolling bearing. When detecting faults of rotating machinery, variation in working conditions leads to the distribution mismatch between training and test data. Thus, the diagnosis accuracy of existing deep learning models deteriorates greatly. To address that, we propose a novel ensemble algorithm. The ensemble algorithm employs deep convolutional extreme learning machine (DCELM) as base learners to learn representative features from time-frequency images. Then, a selection scheme is designed to select diverse base learners which are negatively correlated. Meanwhile, by calculating the correlation term using both the source and the target domain data, the attained ensemble diversity is also valid in target domains. The proposed ensemble algorithm is applied to detect faults of rotating machinery components in three cases. Results show that it attains the best performance on all cross-condition tasks. On average, its accuracy is 1.9% higher than other state-of-the-art ensemble methods and achieves 3.6% enhancement compared with its base learner. [ABSTRACT FROM AUTHOR]