Three-Dimensional Human Posture Recognition by Extremity Angle Estimation with Minimal IMU Sensor.

Recently, posture recognition technology has advanced rapidly. Herein, we present a novel posture angle calculation system utilizing a single inertial measurement unit and a spatial geometric equation to accurately identify the three-dimensional (3D) motion angles and postures of both the upper and lower limbs of the human body. This wearable system facilitates continuous monitoring of body movements without the spatial limitations or occlusion issues associated with camera-based methods. This posture-recognition system has many benefits. Providing precise posture change information helps users assess the accuracy of their movements, prevent sports injuries, and enhance sports performance. This system employs a single inertial sensor, coupled with a filtering mechanism, to calculate the sensor's trajectory and coordinates in 3D space. Subsequently, the spatial geometry equation devised herein accurately computed the joint angles for changing body postures. To validate its effectiveness, the joint angles estimated from the proposed system were compared with those from dual inertial sensors and image recognition technology. The joint angle discrepancies for this system were within 10° and 5° when compared with dual inertial sensors and image recognition technology, respectively. Such reliability and accuracy of the proposed angle estimation system make it a valuable reference for assessing joint angles.

Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

Enhanced biodegradation of benzo[a]pyrene with Trametes versicolor stimulated by citric acid.

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.

A cavity induced mode hybridization plasmonic sensor for portable detection of exosomes.

Exosomes have been considered as promising biomarkers for cancer diagnosis due to their abundant information from originating cells. However, sensitive and reliable detection of exosomes is still facing technically challenges due to the lack of a sensing platform with high sensitivity and reproducibility. To address the challenges, here we propose a portable surface plasmon resonance (SPR) sensing of exosomes with a three-layer Au mirror/SiO2 spacer/Au nanohole sensor, fabricated by an economical polystyrene nanosphere self-assembly method. The SiO2 spacer can act as an optical cavity and induce mode hybridization, leading to excellent optimization of both sensitivity and full width at half maximum compared with normal single layer Au nanohole sensors. When modified with CD63 or EpCAM aptamers, a detection of limit (LOD) of as low as 600 particles/µL was achieved. The sensors showed good capability to distinguish between non-tumor derived L02 exosomes and tumor derived HepG2 exosomes. Additionally, high reproducibility was also achieved in detection of artificial serum samples with RSD as low as 2%, making it feasible for clinical applications. This mode hybridization plasmonic sensor provides an effective approach to optimize the detection sensitivity of exosomes, pushing SPR sensing one step further towards cancer diagnosis.

Causal inference and mechanism for unraveling the removal of four pesticides from lettuce (Lactuca sativa L.) via ultrasonic processing and various immersion solutions.

This study explores the reduction of carbamates (CAs) and pyrethroids (PYs) - commonly used pesticides - in lettuce using various immersion solutions and ultrasonic processing. It also examines the role of machine learning and molecular docking in understanding the mechanisms of pesticide reduction. The results revealed that the highest reduction of both CAs and PYs exceeded 80 % on lettuce leaves. In most samples, the reduction increased with the power of ultrasonic processing and processing time. The results of machine learning models (XGBoost and SHAP) showed that during the immersion cleaning of CAs and PYs, as well as during both immersion cleaning and ultrasonic processing of CAs + PYs, the reduction was most influenced by the initial pesticide levels and immersion time. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of lettuce's wax layer identified 24 compounds, including fatty alcohols, fatty acids, fatty acid esters, and triterpenoids. Despite the absence of active sites, the lipophilic nature of long-chain aliphatic compounds aids in pesticide binding, while triterpenoids form strong hydrogen bonds with pesticides, indicating a robust adsorption on the lettuce surface. This study aims to offer insights into the efficient removal of chemical pesticide residues from fruits and vegetables, addressing critical concerns for food safety and human health.

Understanding the log file data from educational and psychological computer-based testing: A scoping review protocol.

With the advancement of computer-based testing, log file data has drawn considerable attention from researchers. Although emerging studies have begun to explore log file data, there is a gap in the exploitation of log file data for capturing and understanding participants' cognitive processes. The debate on how to maximize insights from log file data has not yet reached a consensus. Therefore, we present this protocol for a scoping review that aims to characterize the application of log file data in current publications, including the data pre-processing techniques, analytical methodologies, and theoretical frameworks used by researchers. This review will also aim to illuminate how log file data can enhance psychological and educational assessments. Our findings will highlight the opportunities and challenges presented by log file data as an emerging and essential source of evidence for future advancements in psychological and educational assessment.

Organic-inorganic hybrid interfaces with π-d electron coupling for preventing metal and sulfur leaching toward enhanced oxygen evolution reaction.

Transition metal sulfides (TMSs) catalysts with high catalytic oxygen evolution reaction (OER) activity have been extensively studied, especially Fe and Co-based sulfides. Fe and Co active sites with a strong synergistic effect, which can adjust the electron density distribution and effectively improve the electrocatalytic OER activity. However, TMSs have poor stability in alkaline environment caused by metal ions and sulfur elements are facilitated to dissolve. In this work, TMSs was modified by polyaniline (PANI) to inhibit the precipitation of iron, cobalt, and sulfur elements and enhance its stability under alkaline conditions. Moreover, π-d structure can also be formed by the coating of PANI, which can further adjust its own electronic structure on the basis of stabilizing the TMSs structure, so as to improve the electrochemical performance, rendering them to stably operate at harsh environment for more than 90 h. These findings offer new guidance for improving the electrocatalytic stability of TMSs.

Cryo-Milled ß-Glucan Nanoparticles for Oral Drug Delivery.

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded ß-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into ß-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the ß-glucan polymers, and the IC50s of drug solution and drug-loaded ß-glucan NPs were calculated as 228.8 ± 31.2 ng·mL-1 and 306.1 ± 46.3 ng·mL-1, respectively. Additionally, the LD50 of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded ß-glucan NPs could achieve a 7.4-fold longer T1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded ß-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled ß-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy.

Decoding the genome of bloodsucking midge Forcipomyia taiwana (Diptera: Ceratopogonidae): Insights into odorant receptor expansion.

Biting midges, notably those within the Ceratopogonidae family, have long been recognized for their epidemiological significance, both as nuisances and vectors for disease transmission in vertebrates. Despite their impact, genomic insights into these insects, particularly beyond the Culicoides genus, remain limited. In this study, we assembled the Forcipomyia taiwana (Shiraki) genome, comprising 113 scaffolds covering 130.4 Mbps-with the longest scaffold reaching 7.6 Mbps and an N50 value of 2.6 Mbps-marking a pivotal advancement in understanding the genetic architecture of ceratopogonid biting midges. Phylogenomic analyses reveal a shared ancestry between F. taiwana and Culicoides sonorensis Wirth & Jones, dating back approximately 124 million years, and highlight a dynamic history of gene family expansions and contractions within the Ceratopogonidae family. Notably, a substantial expansion of the odorant receptor (OR) gene family was observed, which is crucial for the chemosensory capabilities that govern biting midges' interactions with their environment, including host seeking and oviposition behaviors. The distribution of OR genes across the F. taiwana genome displays notable clusters on scaffolds, indicating localized tandem gene duplication events. Additionally, several collinear regions were identified, hinting at segmental duplications, inversions, and translocations, contributing to the olfactory system's evolutionary complexity. Among the 156 ORs identified in F. taiwana, 134 are biting midge-specific ORs, distributed across three distinct clades, each exhibiting unique motif features that distinguish them from the others. Through weighted gene co-expression network analysis, we correlated distinct gene modules with sex and reproductive status, laying the groundwork for future investigations into the interplay between gene expression and adaptive behaviors in F. taiwana. In conclusion, our study not only highlights the unique olfactory repertoire of ceratopogonid biting midges but also sets the stage for future studies into the genetic underpinnings of their unique biological traits and ecological strategies.

Repurposing the diuretic benzamil as an anti-osteosarcoma agent that acts by suppressing integrin/FAK/STAT3 signalling and compromising mitochondrial function.

Aims: Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods: MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results: Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and ß1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion: Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion.

Biodegradation of Trichloroethylene by Trametes versicolor and its Physiological Response to Contaminant Stress.

Trichloroethylene (TCE) poses a potentially toxic threat to humans and the environment and widely exists in contaminated sites. White rot fungi effectively degrade refractory pollutants, while a few research studies use white rot fungi to degrade TCE. In this study, we investigated TCE biodegradation by white rot fungi and the potential influencing factors in the environment and attempted to research the effect of TCE on the physiological characteristics of white rot fungi. White rot fungi (Trametes versicolor, Pseudotrametes gibbosa, Pycnoporus sanguines and Pleurotus ostreatus) were added to the liquid medium for shock culture. The results revealed that T. versicolor exhibited the most pronounced efficacy in removing TCE, with a degradation rate of 81.10% within a 7 d period. TCE induces and is degraded by cytochrome P450 enzymes. High pH and Cr(VI) adversely affected the effectiveness of the biodegradation of TCE, but the salinity range of 0-1% had less effect on biodegradation. Overall, the effectiveness of degradation of TCE by T. versicolor has been demonstrated, and it provides a reference for the application prospects of white rot fungi in TCE-contaminated soils.

Irisin combined index to diagnose central precocious puberty in girls: a cross-sectional study.

BACKGROUND: To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls. METHODS: In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test. RESULTS: Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index. CONCLUSIONS: Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.

Visualizing Nanoscale Interlayer Magnetic Interactions and Unconventional Low-Frequency Behaviors in Ferromagnetic Multishelled Structures.

Precise manipulation of van der Waals forces within 2D atomic layers allows for exact control over electron-phonon coupling, leading to the exceptional quantum properties. However, applying this technique to diverse structures such as 3D materials is challenging. Therefore, investigating new hierarchical structures and different interlayer forces is crucial for overcoming these limitations and discovering novel physical properties. In this work, a multishelled ferromagnetic material with controllable shell numbers is developed. By strategically regulating the magnetic interactions between these shells, the magnetic properties of each shell are fine-tuned. This approach reveals distinctive magnetic characteristics including regulated magnetic domain configurations and enhanced effective fields. The nanoscale magnetic interactions between the shells are observed and analyzed, which shed light on the modified magnetic properties of each shell, enhancing the understanding and control of ferromagnetic materials. The distinctive magnetic interaction significantly boosts electromagnetic absorption at low-frequency frequencies used by fifth-generation wireless devices, outperforming ferromagnetic materials without multilayer structures by several folds. The application of magnetic interactions in materials science reveals thrilling prospects for technological and electronic innovation.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Hybrids of two destructive subterranean termites established in the field, revealing a potential for gene flow between species.

Hybridization between invasive pest species may lead to significant genetic and economic impacts that require close monitoring. The two most invasive and destructive termite species worldwide, Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann), have the potential for hybridization in the field. A three-year field survey conducted during the dispersal flight season of Coptotermes in Taiwan identified alates with atypical morphology, which were confirmed as hybrids of the two Coptotermes species using microsatellite and mitochondrial analyses. Out of 27,601 alates collected over three years, 4.4% were confirmed as hybrid alates, and some advanced hybrids (>F1 generations) were identified. The hybrid alates had a dispersal flight season that overlapped with the two parental species 13 out of 15 times. Most of the hybrid alates were females, implying that mating opportunities beyond F1 may primarily be possible through female hybrids. However, the incipient colony growth results from all potential mating combinations suggest that only backcross colonies with hybrid males could sometimes lead to brood development. The observed asymmetrical viability and fertility of hybrid alates may critically reduce the probability of advanced-hybrid colonies being established in the field.

Enhanced bioremediation of organically combined contaminated soil by white rot fungal agent: physiological characteristics and contaminants degradation.

Microbial remediation of organically combined contaminated sites is currently facing technical challenges. White rot fungi possess broad-spectrum degradation capabilities, but most of the studies are conducted on polluted water bodies, and few research focus on the degradation of combined organically contaminated soils. This study aimed to investigate the physiological changes in Trametes versicolor to enhance its simultaneous degradation ability towards benzo(a)pyrene (BaP) and TPH. The results demonstrated that Trametes versicolor, when subjected to liquid fermentation, achieved an 88.08% degradation of individual BaP within 7 days. However, under the combined contamination conditions of BaP and TPH, the BaP degradation rate decreased to 69.25%, while the TPH degradation rate was only 16.95%. Furthermore, the degradation rate of BaP exhibited a significant correlation with the extracellular protein concentration and laccase activities. Conversely, the TPH degradation rate exhibited a significant and positive correlation with the intracellular protein concentration. Solid-state fermentation utilizing fungal agents proved to be the most effective method for removing BaP and TPH, yielding degradation rates of 56.16% and 15.73% respectively within 60 days. Overall, Trametes versicolor demonstrated a commendable capability for degrading combined PAHs-TPH pollutants, thereby providing theoretical insights and technical support for the remediation of organically combined contaminated sites.

DNA Barcoding Supports "Color-Pattern''-Based Species of Stictochironomus from China (Diptera: Chironomidae).

The genus Stictochironomus (Diptera: Chironomidae) has an almost worldwide distribution, with more than 30 species. However, species delimitation and identification based on the markings on the wings and legs are controversial and uncertain. In this study, we focused on color patterns to review the adults of the genus from China, and two new species (S. trifuscipes sp. nov. and S. quadrimaculatus sp. nov.) are described and figured. DNA barcodes can accurately separate the two new species with specific color patterns. However, heterospecific individuals form a monophyletic cluster in the phylogeny tree. For example, S. maculipennis (Meigen) and S. pictulus (Meigen), which have a lower interspecific genetic divergence, form a single clade. Sequences with the same species name but with high intraspecific distance form more than one phylogenetic clade, such as S. sticticus (Fabricius) of three clades, S. pictulus of four clades, S. akizukii (Tokunaga) and S. juncaii Qi, Shi, and Wang of two clades, might have potential cryptic species diversity. Species delimitation analysis using ASAP, PTP, and GMYC clearly delineated them as separate species. Consequently, color patterns are a good diagnostic characteristic for species delimitation in Stictochironomus. The distance-based analysis shows that a threshold of 4.5-7.7% is appropriate for species delimitation in Stictochironomus. Additionally, an updated key including color pattern variation for male adults of known Stictochironomus species from China is provided.

Enhancing the Repair of Substantial Volumetric Muscle Loss by Creating Different Levels of Blood Vessel Networks Using Pre-Vascularized Nerve Hydrogel Implants.

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.

Optimal Post-Operative Nalbuphine Dose Regimen: A Randomized Controlled Trial in Patients with Laparoscopic Cholecystectomy.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells.

Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.