Search Results (81)

The increasing complexity of highway electromechanical systems has created a critical need to improve the accuracy of resource consumption standards. Traditional deterministic methods often fail to capture inherent variability in resource usage, resulting in significant discrepancies between budget estimates and actual costs. To address this issue for a specific device, this study develops a probabilistic framework based on Monte Carlo simulation, using manual barrier gate installation as a case study. First, probability distribution models for key parameters were established by collecting and statistically analyzing field data. Next, Monte Carlo simulation generated 100,000 pseudo-observations, yielding mean labor consumption of 1.08 workdays (SD 0.29), expansion bolt usage of 6.02 sets (SD 0.97), and equipment shifts of 0.20 (SD 0.10). Comparison with the “Highway Engineering Budget Standards” (JTG/T 3832-2018) revealed deviations of 1% to 4%, and comparison with market bid prices showed errors below 2%. These results demonstrate that the proposed method accurately captures dynamic fluctuations in resource consumption, aligning with both national norms and actual tender data. In conclusion, the framework offers a robust and adaptable tool for cost estimation and resource allocation in highway electromechanical projects, enhancing budgeting accuracy and reducing the risk of cost overruns. Full article

Background: While Bacillus Calmette-Guérin (BCG) remains the first-line therapy for high-risk bladder cancer, 30–40% of patients develop treatment resistance necessitating radical cystectomy, some are not suitable candidates for this procedure. This underscores the critical need for novel therapeutic approaches. Emerging clinical evidence has increasingly supported the therapeutic potential of oncolytic viruses in bladder cancer treatment. Based on this clinical foundation, we investigated the anti-tumor effects of KD01, a novel type 5 recombinant oncolytic adenovirus previously developed by our team engineered to express truncated BID (tBID), in bladder cancer. Methods: The cytotoxic effects and anti-tumor efficacy of KD01 were systematically evaluated across human bladder cancer cell lines, and cell death pathways were investigated by RNA sequencing and validated. Combination therapy studies with cisplatin employed cytotoxic testing. In the final stage, the safety of KD01 bladder instillation was evaluated. Results: KD01 induced bladder cancer cell death through multiple mechanisms, including oncolysis, immunogenic cell death, and mitochondrial apoptosis. At higher doses, KD01 combined with cisplatin synergistically inhibited cancer cell proliferation and induced apoptosis. Additionally, KD01 amplified damage-associated molecular patterns (DAMPs) release and immune activation; the combination with cisplatin further enhanced the process. Safety evaluations showed favorable tolerance to intravesical perfusion with KD01. Conclusions: The dual action of KD01 in directly killing tumor cells and activating anti-tumor immunity underscores its potential as a therapeutic agent. These findings highlight the preclinical efficacy and safety of KD01, informing the design of clinical trials. Full article

Background/Objectives: Bladder cancer (BC), a highly heterogeneous and mutation-prone malignancy, remains a significant therapeutic challenge due to its propensity for recurrence, metastasis, and drug resistance. Natural products, particularly paeonol, a bioactive compound derived from Moutan Cortex in traditional Chinese medicine, have shown promising potential in cancer therapy. This study aims to evaluate the anti-BC effects of paeonol and elucidate its underlying molecular mechanisms. Methods: In vitro experiments were conducted using T24 and J82 BC cell lines to assess paeonol’s effects on cell viability, migration, apoptosis, and cell cycle progression via CCK-8, scratch, flow cytometry, RT-qPCR, and Western blot analyses. In vivo efficacy was evaluated using a xenograft mouse model, with tumor growth monitored and histopathological analysis performed. Results: Paeonol significantly inhibited BC cell proliferation and migration in a dose- and time-dependent manner, with IC₅₀ values of 225 μg/mL (T24) and 124 μg/mL (J82) at 48 h. It induced apoptosis and arrested the cell cycle at the G1 phase, accompanied by upregulation of pro-apoptotic proteins (BID, BAX, BIM, and p53). In vivo, paeonol reduced tumor volume and weight without histopathological abnormalities in vital organs. Conclusions: Paeonol exhibits potent anti-BC activity by apoptotic pathways and by arresting the cell cycle at the G1 phase and inhibiting tumor growth. Its favorable safety profile and multi-target mechanisms highlight its potential as a promising therapeutic candidate for BC. These findings provide a foundation for further clinical development of paeonol-based therapies. Full article

Background and Objective: Mammea siamensis (MS) is a Thai herb used in traditional medicine. Previous studies have reported the antiproliferative effects of its constituents in various cancer cell lines. However, the effects of MS extract on cytotoxicity and molecular mechanisms of apoptosis induction in HCT116 colon cancer cells have not been fully explored. Methods and Results: The cytotoxic effect of MS extract on HCT116 cells was assessed using the MTT assay. MS extract increased cytotoxicity in a concentration-dependent manner. It also induced nuclear morphological changes and disrupted the mitochondrial membrane potential (ΔΨm), as assessed by Hoechst 33342 and JC-1 staining, respectively. These findings indicated that MS extract induced apoptosis, which was further confirmed by flow cytometry showing an increase in the sub-G1 phase. To investigate the expression of signaling proteins, Western blot analysis was conducted. The results showed that MS extract activated caspase activity (caspase-8, -9, and -7) and inhibited PARP activity. Additionally, MS extract upregulated pro-apoptotic proteins (tBid, Bak, and cytochrome c) while downregulating anti-apoptotic proteins (Bcl-2 and Bcl-xL). Mechanistic studies revealed that MS extract activated MAPK pathways while inactivating the PI3K/Akt/NF-κB and GSK-3β/β-catenin pathways. Notably, MS extract also inhibited V-ATPases, as evaluated by acridine orange staining and Western blot analysis. Conclusions: Our findings suggest that MS extract induces apoptosis via the activation of both intrinsic and extrinsic pathways associated with the key signaling pathways. Therefore, MS extract shows potential as a therapeutic agent for colon cancer. Full article

The BH3-interacting domain death agonist (Bid), a proapoptotic signaling molecule of the B-cell lymphoma 2 (Bcl-2) family, is a key regulator of mitochondrial outer membrane (MOM) permeability. Uniquely positioned at the intersection of extrinsic and intrinsic apoptosis pathways, Bid links death receptor signaling to the mitochondria-dependent cascade and can also be activated by endoplasmic reticulum (ER) stress. In its active forms, cleaved Bid (cBid) and truncated Bid (tBid), it disrupts MOM integrity via Bax/Bak-dependent and independent mechanisms. Apoptosis plays a dual role in viral infections, either promoting or counteracting viral propagation. Consequently, viruses modulate Bid signaling to favor their replication. The deregulation of Bid activity contributes to oncogenic transformation, inflammation, immunosuppression, neurotoxicity, and pathogen propagation during various viral infections. In this work, we explore Bid’s structure, function, activation processes, and mitochondrial targeting. We describe its role in apoptosis induction and its involvement in infections with multiple viruses. Additionally, we discuss the therapeutic potential of Bid in antiviral strategies. Understanding Bid’s signaling pathways offers valuable insights into host–virus interactions and the pathogenesis of infections. This knowledge may facilitate the development of novel therapeutic approaches to combat virus-associated diseases effectively. Full article

Out-of-season breeding is an effective method for addressing seasonal shortages of fry in aquaculture species such as largemouth bass (LMB) for year-round production. Off-season breeding of LMB can be achieved by subjecting breeding LMB to prolonged low-temperature conditions; however, this can alter reproductive rhythms, affecting the quality of their sperm and leading to a decrease in reproductive efficiency. Therefore, it is crucial to investigate issues such as the damage to the testes and the related mechanisms caused by low-temperature stress during out-of-season breeding. In this experiment, we assessed the changes in the testes during this time in LMB by comparing reproductive rhythms, testicular histomorphology, ultrastructure, antioxidant capacity and apoptosis. We synthesized measurements of LMB from three identically treated cement ponds and fish exposed to water temperatures of 13–16 °C to assess the changes in the testes. The results showed that (1) out-of-season reproduction delayed sperm production and promoted sperm redevelopment in LMB, various hormone levels have changed over time (e.g., LH, FSH, and T). (2) The head plasma membrane of LMB spermatozoa was separated, and the middle mitochondria were swollen. (3) The expression levels of antioxidant enzymes (cat, sod, and gpx) were upregulated, and oxidative stress occurred in LMB. (4) The expression levels of apoptosis genes (e.g., bax, bcl2, and caspase3) were upregulated, and apoptosis occurred in LMB due to off-season breeding. Moreover, important genes of the mitochondrial apoptosis pathway (bid, CYT-C) were upregulated, indicating that spermatozoan apoptosis in LMB was probably achieved through the mitochondrial apoptosis pathway. These results suggest the delays, damage, and regeneration of LMB testes. Our findings provide new insights into the molecular mechanisms that trigger changes in sperm quality during out-of-season breeding in fish. Full article

Background: Despite accumulating evidence correlating oxidative stress with lupus disease activity, the brain redox pathways are still poorly investigated. Cinnamomum cassia, a widely used spice with powerful antioxidant properties, could be a novel therapeutic candidate in lupus. Methods: C57BL/6J female mice were divided into five groups: sham, sham-cinnamon, lupus, lupus-cinnamon starting from induction, and lupus-cinnamon starting two weeks before induction. Lupus was induced by skin application on the right ear with 1.25 mg of 5% imiquimod cream three times per week for six weeks. Cinnamomum cassia was given orally, five days per week, at 200 mg/kg. Results: Concomitant to TLR7-MYD88 pathway activation, the p-NRF2/NRF2 and p-FOXO3/FOXO3 ratios were increased in the hippocampus and alleviated by cinnamon treatment. BCL-2 positivity was enhanced in hippocampal neurons and reversed only by preventive cinnamon administration. In vitro, exposure of hippocampal cells to the plasma of different groups induced a surge in oxidative stress. This was associated with an increased t-BID/BID ratio. Cinnamon treatment, particularly in the preventive arm, normalized these modifications. Conclusions: Our study shows a neuroprotective effect of cinnamon by rescuing brain redox and apoptosis homeostasis in lupus, paving the way for its use as a natural therapeutic compound in the clinical management of lupus. Full article

With the widespread adoption of blockchain technology, its public ledger characteristic enhances transaction transparency but also amplifies the risk of privacy breaches. Attackers can infer users’ real identities and behaviors by analyzing public transaction patterns and address relationships, posing a severe threat to users’ privacy and security, and thus hindering further advancements in blockchain applications. To address this challenge, covert communication has emerged as an effective strategy for safeguarding the privacy of blockchain users and preventing information leakage. But existing blockchain-based covert communication schemes rely solely on the immutability of blockchain itself for robustness and suffer from low transmission efficiency. To tackle these issues, this paper proposes a stealthy communication model with blockchain smart contract for bidding systems. The model initiates by preprocessing sensitive information using a secret-sharing algorithm-the Shamir (t, n) threshold scheme-and subsequently embeds this information into bidding amounts, facilitating the covert transfer of sensitive data. We implemented and deployed this model on the Ethereum platform and conducted comprehensive performance evaluations. To assess the stealthiness of our approach, we employed a suite of statistical tests including the CDF, the Kolmogorov–Smirnov test, Welch’s t-test and K–L divergence. These analyses confirmed that amounts carrying concealed information were statistically indistinguishable from regular transactions, thus validating the effectiveness of our solution in maintaining the anonymity and confidentiality of information transmission within the blockchain ecosystem. Full article

Effective cancer therapy with limited adverse effects is a major challenge in the medical field. This is especially complicated by the development of acquired chemoresistance. Understanding the mechanisms that underlie these processes remains a major effort in cancer research. In this review, we focus on the dual role that Bid protein plays in apoptotic cell death via the mitochondrial pathway, in oncogenesis and in cancer therapeutics. The BH3 domain in Bid and the anti-apoptotic mitochondrial proteins (Bcl-2, Bcl-XL, mitochondrial ATR) it associates with at the outer mitochondrial membrane provides us with a viable target in cancer therapy. We will discuss the roles of Bid, mitochondrial ATR, and other anti-apoptotic proteins in intrinsic apoptosis, exploring how their interaction sustains cellular viability despite the initiation of upstream death signals. The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria. Full article

Osteosarcoma malignancy currently represents a major health problem; therefore, the need for new therapy approaches is of great interest. In this regard, the current study aims to evaluate the anti-neoplastic potential of a newly developed phosphinic acid derivative (2-carboxyethylphenylphosphinic acid) and, subsequently, to outline its pharmaco-toxicological profile by employing two different in vitro human cell cultures (keratinocytes—HaCaT—and osteosarcoma SAOS-2 cells), employing different techniques (MTT assay, cell morphology assessment, LDH assay, Hoechst staining and RT-PCR). Additionally, the results obtained are compared with three commercially available phosphorus-containing compounds (P1, P2, P3). The results recorded for the newly developed compound (P4) revealed good biocompatibility (cell viability of 77%) when concentrations up to 5 mM were used on HaCaT cells for 24 h. Also, the HaCaT cultures showed no significant morphological alterations or gene modulation, thus achieving a biosafety profile even superior to some of the commercial products tested herein. Moreover, in terms of anti-osteosarcoma activity, 2-carboxyethylphenylphosphinic acid expressed promising activity on SAOS-2 monolayers, the cells showing viability of only 55%, as well as apoptosis features and important gene expression modulation, especially Bid downregulation. Therefore, the newly developed compound should be considered a promising candidate for further in vitro and in vivo research related to osteosarcoma therapy. Full article

Rebar quantity estimation is pivotal for determining the cost of construction projects and is essential for bidding purposes. A bar bending schedule plays a crucial role by providing rebar information and bending instructions, facilitating efficient procurement. Traditional methods, which rely on manually extracting data from 2D (two-dimensional) drawings, are error-prone and hinder construction productivity. This study utilized a special length approach to yield optimal rebar consumption, resulting in a total rebar order of 19,582.427 t and minimizing rebar waste to 0.77%. Additionally, this method saved 3000.22 t of rebar compared to traditional methods, using only stock lengths. To enhance the accuracy and efficiency, a 3D (three-dimensional) model was developed in a Building Information Modeling (BIM) environment to prepare a Bar Bending Schedule (BBS) automatically, integrated with an Application Programming Interface (API) for data entry to eliminate manual errors. The efficacy of the proposed algorithm was confirmed by comparing the rebar quantities it generated with those obtained from optimization calculations. The results demonstrated a mean absolute error of 0.017 and a mean absolute percentage error of 1.13%, validating the algorithm’s precision. Furthermore, this method reduced the manpower required for BBS preparation by 33.33%, highlighting its potential to revolutionize construction workflow efficiency and accuracy. Full article

Farming is a major sector required for any nation to become self-sustainable. Quality seeds heavily influence the effectiveness of farming. Seeds cultivated by breeders pass through several entities in order to reach farmers. The existing seed supply chain is opaque and intractable, which not only hinders the growth of crops but also makes the life of a farmer miserable. Blockchain has been widely employed to enable fair and secure transactions between farmers and buyers, but concerns related to transparency and traceability in the seed supply chain, counterfeit seeds, middlemen involvement, and inefficient processes in the agricultural ecosystem have not received enough attention. To address these concerns, a blockchain-based solution is proposed that brings breeders, farmers, warehouse owners, transporters, and food corporations to a single platform to enhance transparency, traceability, and trust among trust-less parties. A smart contract updates the status of seeds from a breeder from $submitted$ to $approved$. Then, a non-fungible token (NFT) corresponding to approved seeds is minted for the breeder, which records the date of cultivation and its owner (breeder). The NFT enables farmers to keep track of seeds right from the date of their cultivation and their owner, which helps them to make better decisions about picking seeds from the correct owner. Farmers directly interact with warehouses to purchase seeds, which removes the need for middlemen and improves the trust among trust-less entities. Furthermore, a tender for the transportation of seeds is auctioned on the basis of the priority location $lo{c}_p$, Score, and bid_amount of every transporter, which provides a fair chance to every transporter to restrict the monopoly of a single transporter. The proposed system achieves immutability, decentralization, and efficiency inherently from the blockchain. We implemented the proposed scheme and deployed it on the Ethereum network. Smart contracts deployed over the Ethereum network interact with React-based web pages. The analysis and results of the proposed model indicate that it is viable and secure, as well as superior to the current seed supply chain system. Full article

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect. Full article

IoT (Internet-of-Things)-powered devices can be exploited to connect vehicles to smart city infrastructure, allowing vehicles to share their intentions while retrieving contextual information about diverse aspects of urban viability. In this paper, we place ourselves in a transient scenario in which next-generation vehicles that are able to communicate with the surrounding infrastructure coexist with traditional vehicles with limited or absent IoT capabilities. We focus on intersection management, in particular on reusing existing traffic lights empowered by a new management system. We propose an auction-based system in which traffic lights are able to exchange contextual information with vehicles and other nearby traffic lights with the aim of reducing average waiting times at intersections and consequently overall trip times. We use bid propagation to improve standard vehicle trip times while allowing emergency vehicles to free up the way ahead without needing ad hoc system for such vehicle, only an increase in their budget. The proposed system is then tested against two baselines: the classical Fixed Time Control system currently adopted for traffic lights, and an auction strategy that does not exploit traffic light coordination. We performed a large set of experiments using the well known MATSim transport simulator on both a synthetic Manhattan map and on a map we built of an urban area located in Modena, Northern Italy. Our results show that the proposed approach performs better than the classical fixed time control system and the auction strategy that does not exploit coordination among traffic lights. Full article

Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, have potential anticancer properties. Our study investigated the in vitro cytotoxic potential and mode of action of HAs extracts containing anthocyanins in colorectal cancer cells. The results showed that Hibiscus anthocyanin-rich extracts induced apoptosis in human colorectal cancer cells through the activation of multiple signaling pathways of AMPK. We observed the dose–response and time-dependent induction of apoptosis with HAs. Subsequently, the activation of Fas-mediated proteins triggered apoptotic pathways associated with Fas-mediated apoptosis-related proteins, including caspase-8/tBid. This caused the release of cytochrome C from the mitochondria, resulting in caspase-3 cleavage and apoptosis activation in intestinal cancer cells. These data elucidate the relationship between Has’ regulation of apoptosis-related proteins in colorectal cancer cells and apoptotic pathways. Full article