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Abstract Introduction Urine-derived exosomes could potentially be biomarkers for bladder cancer (BC) diagnosis. This study aimed to systematically evaluate the diagnostic worth of urine-derived exosomes in BC patients through a meta-analysis of diverse studies. Methods A systematic search was carried out in PubMed, Web of Science, Embase, Cochrane, and CNKI databases to obtain the literature concerning the diagnosis of BC via urine-derived exosomes. A literature retrieval strategy was devised to pick articles and extract needed data from the literature. QUADS-2 was used to evaluate the quality of the included literatures, and the aggregated diagnostic effect was assessed by calculating the area under the aggregated SROC curve. All statistical analyses and plots were conducted with STATA 14.0 and RevMan5.3. Results A total of 678 articles were retrieved by means of the search strategy of the online database. Through screening, 21 articles were obtained, involving 3348 participants and 77 studies. The meta-analysis of the results indicated that urinary exosomes had a combined sensitivity of 0.75, a specificity of 0.77, and a combined AUC of 0.83 for the diagnosis of BC, suggesting that urine-derived exosomes have a relatively satisfactory diagnostic effect in the detection of BC. Among the subgroups classified by biomarker, long non-coding RNAs (lncRNAs) had the highest comprehensive sensitivity (SEN = 0.78), and miRNAs had the highest comprehensive specificity (SPN = 0.81). In other subgroup analyses, the biomarker panel for multiple exosomes combined diagnosis demonstrated the best diagnostic efficacy, with a combined the area under the curve ( AUC) of 0.87. Conclusions As a novel biomarker, urine-derived exosomes have significant diagnostic prospects in the diagnosis of BC. Nevertheless, their application in clinical settings still demands a considerable number of clinical trials to confirm their clinical feasibility and practicability.

Avermectin (AVM), a compound derived from the fermentation of Avermectin Streptomyces, has insecticidal, acaricidal, and nematicidal properties. Widely employed in agriculture, it serves as an effective and broad-spectrum insecticide for pest control. Although the toxicity of AVM at low doses may not be readily apparent, prolonged and extensive exposure can result in poisoning. To investigate the toxic effects of AVM on the body, this study established rat models of AVM poisoning with both low and high concentrations of the compound. Fifteen male rats were randomly assigned to one of three groups (n=5 per group): a control group, a low-concentration group, and a high-concentration group. The low-concentration group was administered an oral dose of 2 mg/kg AVM once daily for a duration of seven days, while the high-concentration group received an oral dose of 10 mg/kg AVM once daily for the same period. This study examined the impact of AVM on liver function and gut microbiota in rats using weight monitoring, liver function indicator detection, liver metabolomics sequencing, colon barrier function testing, and gut microbiota sequencing. The findings of this study demonstrated that exposure to 2 or 10 mg/kg AVM for seven days can lead to a notable decrease in rat weight, as well as induce liver dysfunction and metabolic disturbances. Additionally, AVM exposure can disrupt the composition of the intestinal microbiota and impair the integrity of the colon mucosal barrier, causing downregulation of Occludin expression and upregulation of inflammation-related protein expression levels such as IL-1β, Myd88, and TLR4. Furthermore, bioinformatics analysis revealed a significant association between liver dysfunction and dysbiosis of the gut microbiota. These findings have implications for the agricultural use of AVM and its potential contribution to environmental pollution. Consequently, individuals involved in AVM usage should prioritize safety precautions and monitor liver function.

Abstract Background Intravenous lidocaine could be a potential alternative adjuvant to propofol-based sedation for gastroscopy in elderly patients. This study aimed to evaluate the effect of intravenous lidocaine on the median effective dose (ED50) of propofol induction dose in elderly patients undergoing painless gastroscopy. Methods The study included 70 patients aged ≥ 60 years undergoing painless gastroscopy with 64 randomly assigned to either group L (2% lidocaine 1.5 mg/kg, n = 31) or group N (equal volume normal saline, n = 33). All patients received propofol induction following 0.1 μg/kg intravenous sufentanil. The Dixon “up-and-down” sequential method was used, with a 1.5 mg/kg initial induction dose of propofol followed by a 0.1 mg/kg sequential variable dose. The primary endpoint was the ED50 of the propofol induction dose. The total propofol dose, recovery time, adverse events, and local anesthetic intoxication reactions were also recorded. Results The ED50 of propofol induction dose was 0.670 (95% confidence interval [CI] 0.216–0.827) mg/kg in group L and 1.118 (95% CI 0.803–1.232) mg/kg in group N. There was a statistically significant difference between the two groups (p

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1−/−) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Organic phototransistors, renowned for their exceptional biocompatibility, hold promise in phototherapy for tracking the efficacy of photosensitive drugs within treatment areas. Nevertheless, it has been found that organic semiconductors are less effective in detecting ultraviolet (UV) light because of their narrow bandgap. Here, we show that UV photodetection in phototransistors using donor-acceptor (D-A) polymer semiconductors can be significantly enhanced by incorporating PCBM nanocrystals. This integration results in a band mismatch between the nanocrystals and the D-A polymer at the interface. These nanocrystals also demonstrate a notable capability of modulating threshold voltage under UV light. The devices incorporating nanocrystals exhibit a photoresponsivity of 0.16 A/W, surpassing the photoresponsivity of the devices without nanocrystals by 50%. The specific detection rate of devices with nanocrystals is around 2.00 × 1010 Jones, which is twice as high as that of devices without nanocrystals. The presented findings offer a potential avenue to improve the efficiency of polymer phototransistors for UV detection.

Abstract Background EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. Methods A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient’s rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. Results There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. Conclusions In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.

Hepatocellular carcinoma (HCC) has a very high incidence and fatality rate, and in most cases, it is already at an advanced stage when diagnosed. Therefore, early prevention and detection of HCC are two of the most effective strategies. However, the methods recommended in the practice guidelines for the detection of HCC cannot guarantee high sensitivity and specificity except for the liver biopsy, which is known as the “gold standard”. In this review, we divided the detection of HCC into pre-treatment diagnosis and post-treatment monitoring, and found that in addition to the traditional imaging detection and liver biopsy, alpha fetoprotein (AFP), lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), protein induced by vitamin K absence or antagonist-II (PIVKA-II) and other biomarkers are excellent biomarkers for HCC, especially when they are combined together. Most notably, the emerging liquid biopsy shows great promise in detecting HCC. In addition, lactic dehydrogenase (LDH), suppressor of cytokine signaling (SOCS) and other relevant biomarkers may become promising biomarkers for HCC post-treatment monitoring. Through the detailed introduction of the diagnostic technology of HCC, we can have a detailed understanding of its development process and then obtain some enlightenment from the diagnosis, to improve the diagnostic rate of HCC and reduce its mortality.

Abstract Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage‐based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor‐transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN‐γ‐treated macrophages, making macrophage‐based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF‐κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

Abstract Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4+ and CD8+ T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.

Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel–mediated neural circuit basis for RIH that can guide analgesic development.

Abstract Judging the maturity level of each hand‐wrist reference bone is the core issue in bone age assessment. Relying on the superiority of convolutional neural networks in feature representation, deep learning is widely studied for the automatic bone age assessment. However, an efficient but complex deep learning network requests a large dataset with bone‐maturity‐level labels for training, restricting its large‐scale application in bone maturity classification. For this reason, we transform the bone‐maturity‐level classification problem into the similarity matching problem. Also, we propose a general structure based on Siamese network by merging two inputs into a two‐channel input and introducing a dual attention mechanism, to create an Attentional Two‐Channel Network (ATC‐Net). This paper takes the intermediate phalanges III as an example to assess the performance of the similarity matching method and the ATC‐Net. Experiments show that our method can perform better on small datasets, which effectively makes up for the data shortage problem. The ATC‐Net used for classification significantly reduces the evaluation time compared with other classical networks. It reduces the time of assessing one sample by about 49% as compared to VGG‐16. And more importantly, it achieves the highest classification accuracy of 92.74% among all investigated networks.

Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer’s solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer’s solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear.Objective: To compare the effects of sodium bicarbonate Ringer’s solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation.Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively.Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38–0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006).Conclusion: Sodium bicarbonate Ringer’s solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation.

Background: This study aimed to compare the effects of different depths of sedation during propofol anesthesia on postoperative recovery 24 h after knee arthroscopy day surgery in adult patients.Methods: This prospective randomized controlled trial involved 126 patients (ASA physical status 1–2) who were scheduled to undergo arthroscopic day surgery. Patients were randomly divided into two groups: the light-sedation (L-Group) or deep-sedation (D-Group). In the L-group, the bispectral index values were kept in the range of 50–59; in the D-group, the bispectral index values were maintained in the range of 40–49. The Quality of Recovery-15 (QoR-15) score assessed 24 h postoperatively using a 15-item questionnaire was the primary outcome. Secondary outcomes included Athens Insomnia Scale scores, postoperative pain scores, nausea or vomiting.Results: The total QoR-15 score 24 h postoperatively was similar in the two groups (L-group median:130, IQR [127–132] vs. D-group median:131, IQR [126–135], p = 0.089). But among the five dimensions of the QoR-15, physiological comfort was significantly better in the D-group than L-group (p < 0.001). The time to open eyes (p < 0.001), follow the command (p < 0.001) and to extubation (p < 0.001) after surgery in the L-group were shorter than the D-group. The Athens Insomnia Scale scores (p < 0.001) and incidence of dreaming (p = 0.041) at the first postoperative night in the L-group was significantly higher than those in the D-group. Propofol consumption in the L-group was less than D-group (p < 0.001).Conclusion: For patients undergoing arthroscopic day surgery, general anesthesia with high-bispectral-index (50–59) cannot improve the total QoR-15 score 24 h postoperatively after surgery, but can lessen propofol consumption, reduce the time of extubation and anesthesia recovery period, compared with low-bispectral-index (40–49). Patients exposed to general anesthesia with low-bispectral-index values (40–49) may have better quality sleep and physical comfort than those with high-bispectral-index values (50–59).Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=126526, identifier ChiCTR2100046340

Abstract Background Highly structured electroencephalography (EEG) oscillations can occur in adults during etomidate-induced general anesthesia, but the link between these two phenomena is poorly understood. Therefore, in the present study, we investigated the electroencephalogram dynamics of etomidate-induced loss of consciousness (LOC) in order to understand the neurological mechanism of etomidate-induced LOC. Methods This study is a prospective observational study. Etomidate-induced anesthesia was performed on eligible patients undergoing elective surgery. We analyzed EEG data from 20 patients who received etomidate for the induction of general anesthesia. We used power spectra and coherence methods to process and analyze the EEG data. Our study was based on 4-channel EEG recordings. Results Compared with the baseline (awake period), etomidate induced an increase in power in delta, theta, alpha and beta waves during LOC. Compared with the awake period, the delta-wave (1–4 Hz), alpha-wave(8–13 Hz), and theta-wave(4–8 Hz) coherence increased significantly during LOC, while the slow-wave (

Liver ischemia-reperfusion injury (IRI) is a major complication of liver trauma, resection, and transplantation. IRI may lead to liver dysfunction and failure, but effective approach to address it is still lacking. To better understand the cellular and molecular mechanisms of liver IRI, functional roles of numerous cell types, including hepatocytes, Kupffer cells, neutrophils, and sinusoidal endothelial cells, have been intensively studied. In contrast, hepatic stellate cells (HSCs), which are well recognized by their essential functions in facilitating liver protection and repair, have gained less attention in their role in IRI. This review provides a comprehensive summary of the effects of HSCs on the injury stage of liver IRI and their associated molecular mechanisms. In addition, we discuss the regulation of liver repair and regeneration after IRI by HSCs. Finally, we highlight unanswered questions and future avenues of research regarding contributions of HSCs to IRI in the liver.

Interferon-γ (IFN-γ)-activated macrophages restrain the replication of intracellular parasites and disrupt the integrity of vacuolar pathogens. The growth of the less virulent type II strain of Toxoplasma gondii (such as ME49) was strongly inhibited by IFN-γ-activated murine macrophages. However, the mechanism of resistance is poorly understood. Immunity-related GTPases (IRGs) as well as guanylate-binding proteins (GBPs) contributed to this antiparasitic effect. Previous studies showed the cassette of autophagy-related proteins including Atg7, Atg3, and Atg12-Atg5-Atg16L1 complex, plays crucial roles in the proper targeting of IFN-γ effectors onto the parasitophorous vacuole (PV) membrane of Toxoplasma gondii and subsequent control of parasites. TgCDPK3 is a calcium dependent protein kinase, located on the parasite periphery, plays a crucial role in parasite egress. Herein, we show that the less virulent strain CDPK3 (ME49, type II) can enhance autophagy activation and interacts with host autophagy proteins Atg3 and Atg5. Infection with CDPK3-deficient ME49 strain resulted in decreased localization of IRGs and GBPs around PV membrane. In vitro proliferation and plaque assays showed that CDPK3-deficient ME49 strain replicated significantly more quickly than wild-type parasites. These data suggested that TgCDPK3 interacts with the host Atg3 and Atg5 to promote the localization of IRGs and GBPs around PV membrane and inhibits the intracellular proliferation of parasites, which is beneficial to the less virulent strain of Toxoplasma gondii long-term latency in host cells.

Abstract Background Lung cancer has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Therapies for lung cancer have relatively poor outcomes and further improvements are required. Circular RNAs have been reported to participate in the occurrence and progression of cancer. Information on the functions and mechanism of circRNAs in lung cancer is limited and needs more exploration. Methods We detected expression of genes and proteins by qPCR and western blot. Function of circSATB2 was investigated using RNA interference and overexpression assays. Location of circSATB2 was assessed by fluorescence in situ hybridization (FISH). Interaction of circSATB2, miR-326 and FSCN1 was confirmed by dual-luciferase reporter assay. Results Data from the investigation showed that circSATB2 was highly expressed in NSCLC cells and tissues. circSATB2 positively regulated fascin homolog 1, actin-bundling protein 1 (FSCN1) expression via miR-326 in lung cancer cells. Furthermore, circSATB2 can be transferred by exosomes and promote the proliferation, migration and invasion of NSCLC cells, as well as induce abnormal proliferation in normal human bronchial epithelial cells. Also, circSATB2 was highly expressed in serumal exosomes from lung cancer patients with high sensitivity and specificity for clinical detection and was related to lung cancer metastasis. Conclusions circSATB2 participated in the progression of NSCLC and was differentially expressed in lung cancer tissue and serumal exosomes. circSATB2 may be potential biomarker for the diagnosis of NSCLC.

In forensic practice, the identification of antemortem burns and postmortem burns is of the utmost importance. Reports from previous studies have shown that miRNAs, with lengths stretching over 18–25 nucleotides, are highly stable and resistant to degradation. However, there has been little research into the application of miRNAs in identifying antemortem and postmortem burns. This study compared the expression of miR-711 and miR-183-3p levels in mouse and postmortem human burned skins using RT-qPCR assay. RT-qPCR examination of burned mouse skins showed that increased miR-711 and miR-183-3p expression in comparison to intact skin tissues. The increased expressions of these two miRNAs were observed until 120 h after death in burned mouse skins, whereas no significant changes were found in postmortem burned skins. In human burned skins, the increased levels of these two miRNAs at 48 h following autopsy occurred in 19 of 26 subjects, which appeared to be related to the severity of the burn. These findings suggest that miR-711 and miR-183-3p may act as biomarkers for vital reaction of skin burn.Key points This study investigated miR-711 and miR-183-3p levels in mouse and postmortem human burned skins using RT-qPCR. Increased miR-711 and miR-183-3p levels were observed in burned mouse skins. The increased expressions of these two miRNAs were observed until 120 h after death in burned mouse skin. The increased levels of these two miRNAs were observed until 48 h after autopsy in 19 of 26 forensic cases, which appeared to be related to the severity of the burn.

Adopting proton exchange membrane fuel cells fuelled by hydrogen presents a promising solution for the shipping industry’s deep decarbonisation. However, the potential safety risks associated with hydrogen leakage pose a significant challenge to the development of hydrogen-powered ships. This study examines the safe design principles and leakage risks of the hydrogen gas supply system of China’s first newbuilt hydrogen-powered ship. This study utilises the computational fluid dynamics tool FLACS to analyse the hydrogen dispersion behaviour and concentration distributions in the hydrogen fuel cell room based on the ship’s parameters. This study predicts the flammable gas cloud and time points when gas monitoring points first reach the hydrogen volume concentrations of 0.8% and 1.6% in various leakage scenarios, including four different diameters (1, 3, 5, and 10 mm) and five different directions. This study’s findings indicate that smaller hydrogen pipeline diameters contribute to increased hydrogen safety. Specifically, in the hydrogen fuel cell room, a single-point leakage in a hydrogen pipeline with an inner diameter not exceeding 3 mm eliminates the possibility of flammable gas cloud explosions. Following a 10 mm leakage diameter, the hydrogen concentration in nearly all room positions reaches 4.0% within 6 s of leakage. While the leakage diameter does not impact the location of the monitoring point that first activates the hydrogen leak alarm and triggers an emergency hydrogen supply shutdown, the presence of obstructions near hydrogen detectors and the leakage direction can affect it. These insights provide guidance on the optimal locations for hydrogen detectors in the fuel cell room and the pipeline diameters on hydrogen gas supply systems, which can facilitate the safe design of hydrogen-powered ships.

Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPARα involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPARα) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPARα, thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPARα activation could be an effective therapy against hepatic ischemia/reperfusion injury.

Toxoplasma gondii can infect almost all endotherm organisms including humans and cause life-threatening toxoplasmosis in immunocompromised individuals, which leads to serious public health problems. Developing an excellent vaccine against this disease is impending. In present study, we formulated a cocktail protein vaccine including the TgMIF, TgCDPK3, and Tg14-3-3 proteins, which play critical roles in T. gondii infection. The recombinant protein vaccines were constructed and assessed by vaccination in BALB/c mice. We organized the mice in various protein combination groups of vaccines, and all mice were immunized with corresponding proteins at 0, 2, and 4 weeks. The specific protective effects of the vaccines on mice against T. gondii were analyzed by the mensuration of cytokines, serum antibodies, splenocyte proliferation assay, survival time, and parasite cyst burden of mice after the challenge. The study indicated that mice immunized with all three multicomponent proteins vaccine triggered a strong immune response with highest levels of IFN-γ production and IgG antibody compared with the other two protein combinations and controls. Moreover, there was an increase in IL-4 production and antigen-specific lymphocyte proliferation. The parasite cysts were significantly reduced (resulting in an 82.7% reduction), and survival time was longer in immunized mice with three multicomponent proteins compared with the other groups of mice. The enhanced humoral and cell-mediated immunity indicated that the protein cocktail vaccine containing three antigens provided effective protection for mice. These results indicated that recombinant TgMIF, TgCDPK3, and Tg14-3-3 multicomponent proteins were potential candidates for vaccine against toxoplasmosis.

The therapeutic approach of liver fibrosis is still an unsolved clinical problem worldwide. Notably, the accumulation of extracellular matrix (ECM) in the liver is mediated by the production of cytokines and growth factors, such as transforming growth factor-β1 (TGF-β1) in hepatic stellate cells (HSCs). Ring finger protein 2 (RNF2) was identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), mediating the monoubiquitination of histone H2A. In recent years, a growing amount of evidence suggests that RNF2 may play an important role in multiple pathological processes involved in cancer. Here, we explored the role of RNF2 in liver fibrogenesis and its potential mechanisms. The results showed that RNF2 was up-regulated in human fibrotic liver tissue. Knockdown of RNF2 led to a decreasing expression of collagen1 and α-smooth muscle actin (α-SMA) in LX-2 cells, which was upregulated by RNF2 overexpression. Moreover, RNF2 overexpression significantly promoted TGF-β1-induced LX-2 cell proliferation but decreased apoptosis. Furthermore, knockdown of RNF2 inhibited the activation of ERK/p38 signaling pathways induced by TGF-β1. These data suggested that RNF2 is an effective pro-fibrogenic factor for HSC activation via ERK/p38 signaling pathway. RNF2 inhibition might be a promising therapeutic target for liver fibrosis.

Fine particulate matter (PM2.5) has been verified to augmented the incidence of pneumonia, asthma, pulmonary fibrosis, and other pulmonary diseases. Airway inflammation is the pathological basis of the respiratory system, and understanding the molecular mechanisms responsible for airway inflammation may thus support the diagnosis and treatment of respiratory diseases. In our study, human bronchial epithelial cells (BEAS-2B) were exposed to various concentrations of PM2.5 for 48 h. PM2.5 entered the cells, resulting in increased production of interleukin 6 (IL-6) and interleukin 8 (IL-8) and decreased the expression of circular RNA 406961 (circ_406961). Further, PM2.5 with a concentration of 75 μg/mL was applied to mechanism study. Functional experiments further confirmed that circ_406961 inhibited PM2.5-induced BEAS-2B cell inflammation. RNA pull-down and mass spectrometry showed that circ_406961 interacted with interleukin enhancer-binding factor 2 (ILF2), which could regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase 8 (MAPK8, JNK). Our studies showed that circ_406961 inhibited activation of STAT3/JNK pathways via interacting with ILF2 protein, thereby inhibiting the PM2.5-induced inflammatory reaction.

Due to the influence of the irregular shapes and the adjacent positions of the wrist reference bones, it is difficult for the expert to accurately estimate the mature indication of the wrist reference bones of the minor. How to precisely segment the reference bones of the minor is a challenge. For this problem, the ARU-Net for wrist reference bone segmentation is proposed. First, we extract the reference bone ROI by Faster R-CNN. Then, the pre-processed ROI is fed into ARU-Net for segmentation. On the basis of traditional U-Net, ARU-Net adds residual mapping and attention mechanism, which improves the utilization rate of features and the accuracy of reference bone segmentation. Finally, a post-processing method including the flood fill algorithm and the morphological operation is used to eliminate jagged edges and holes in the segmented result. The hamate is one of the most difficult reference bones to segment in the wrist. This paper takes it as an example to assess the performance of ARU-Net. Experiments show that compared with FCN, U-Net and ResUnet, the accuracy and F1 scores of ARU-Net are higher. The accuracy rate is 96.4%, and the F1 score is 0.953. The post-processing method can further improve the result. Finally, the accuracy rate reaches 96.5%, and the F1 score reaches 0.954. In order to verify the segmentation stability of ARU-Net, it is also applied to the segmentation of the radius and the capitate. RU-Net can precisely segment the reference bone, which facilitates the expert to assess its mature indication, so as to accurately evaluate the bone age.

Abstract Circular RNAs are widely expressed in eukaryotic cells and associated with cancer. However, limited studies to date have focused on the potential role of circRNAs in progression of lung cancer. Data from the current investigation showed that circRNA 100146 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and the chemically induced malignant transformed bronchial cell line, 16HBE-T, as well as 40 paired tissue samples of NSCLC. Suppression of circRNA 100146 inhibited the proliferation and invasion of cells and promoted apoptosis. Furthermore, circRNA 100146 could interact with splicing factors and bind miR-361-3p and miR-615-5p to regulate multiple downstream mRNAs. Our collective findings support a role of circRNA 100146 in the development of NSCLC and further demonstrate endogenous competition among circRNA 100146, SF3B3 and miRNAs, providing novel insights into the mechanisms underlying non-small cell lung cancer.

In this study, RNA-sequencing (RNA-seq) was utilized to investigate the effects of luteolin on hepatotoxicity caused by methamphetamine (METH). The rats in METH group were administrated with METH (15 mg/kg, two times per day) via intraperitoneal (i.p.) injections for four consecutive days. The rats in luteolin + METH group were firstly administrated with luteolin (100 mg/kg, once a day) by oral gavage for 3 days before METH treatment. Lueolin attenuated the hepatotoxicity induced by METH via histopathological and biochemical analysis. The results of RNA-seq showed that luteolin could regulate 497 differentially expressed genes (DEGs), and the selected DEGs were mainly enriched in eight pathways, according to KEGG analysis. Furthermore, qRT-PCR was utilized to verify the results of RNA-seq. Six genes were selected as follows: liver enriched antimicrobial peptide 2 (Leap2), fatty acid synthase (Fasn), fatty acid binding protein 5 (Fabp5), patatin like phospholipase domain containing 3 (Pnpla3), myelin basic protein (Mbp) and calmodulin 3 (Calm3). Though because of the design flaws, the luteolin group has not been included, this study demonstrated that luteolin might exert hepato-protective effects from METH via modulation of oxidative phosphorylation, cytochrome P450 and certain signaling pathways.

Abstract Background Previous studies have shown that prolonged time spent on screen-based sedentary behavior was significantly associated with lower health status in children, independent of physical activity levels. The study aimed to explore the individual and environmental correlates of screen time (ST) among 8–19-year-old students in China. Methods The study surveyed ST using a self-administered questionnaire in Chinese students aged 8–19 years; 1063 participants were included in the final analysis. Individual and environmental correlates of ST were assessed using a mixed-effects model (for continuous outcome variables) and multiple logistic regression model (for binary outcome variables). Results Prolonged ST was observed in 14.7% of boys and 8.9% of girls. Of the ST, weekend and mobile phone/tablet use represented 80% and 40%, respectively. A positive relationship was observed between media accessibility and ST in both boys and girls (p < 0.05), whereas the presence of parents/others while using screens was a negative factor for longer ST (p < 0.05). Among the assessed correlates, access to a television (TV) in students’ bedrooms was associated with prolonged total and weekend ST (p < 0.05 and p < 0.001, respectively). However, spending time on a mobile phone/tablet or a computer rather than viewing a TV, along with increased media accessibility, increased ST. Conclusions These results indicate that greater media accessibility was positively associated and the presence of parents/others was negatively associated with prolonged ST in both Chinese boys and girls. Development of new and effective strategies against prolonged ST are required, especially for small screen device-based ST on weekends.

From the perspective of risk control, when hydrogen fuel and fuel cells are used on ships, there is a possibility of low-flash fuel leakage, leading to the risk of explosion. Since the fuel cell space (cabin for fuel cell installations) is an enclosed space, any small amount of leakage must be handled properly. In ship design, area classification is a method of analyzing and classifying the areas where explosive gas atmospheres may occur. If the fuel cell space is regarded as a hazardous area, all the electrical devices inside it must be explosion-proof type, which will make the ship’s design very difficult. This paper takes a Chinese fuel cell powered ship as an example to analyze its safety. Firstly, the leakage rates of fuel cell modules, valves, and connectors are calculated. Secondly, the IEC60079-10-1 algorithm is used to calculate the risk level of the fuel cell space. Finally, the ship and fuel cells are optimized and redesigned, and the risk level of the fuel cell space is recalculated and compared. The result shows that the optimized fuel space risk level could be reduced to the level of the non-hazardous zone.

Objectives. Dexmedetomidine is widely used as an adjunct to general anesthesia. In this study, we evaluated the effects of perioperative dexmedetomidine infusion on postoperative analgesia in patients undergoing lateral thoracotomy for thoracic esophageal cancer. Methods. A total of 62 patients undergoing lateral thoracotomy for thoracic esophageal cancer were randomized to receive adjuvant therapy with either dexmedetomidine (0.5 μg/kg intravenous bolus injection for 10 min before induction of anesthesia, followed by continuous infusion of 0.2–0.4 μg/kg/h until the end of surgery, and 0.06 μg/kg/h for 5 days after surgery) or equal volumes of saline. Acute postoperative pain was treated with patient-controlled intravenous sufentanil and flurbiprofen axetil. The primary outcomes of this study were the numbers of analgesic requirements in the first postoperative 72 h. Results. Perioperative dexmedetomidine did not decrease the numbers of analgesic requirements in the first postoperative 72 h (dexmedetomidine group: 12.14 ± 4.76, saline group: 10.89 ± 5.66; p=0.367). Likewise, the groups did not differ with respect to total postoperative analgesic requirements, postoperative pain, perioperative inflammation, blood cell count, incidence of adverse events, surgical recovery (assessed at postoperative days 2 and 5 using the surgical recovery scale), length of hospital stay, hospital cost, incidence of chronic pain, or quality of life. Notably, dexmedetomidine had beneficial effects on decreasing intraoperative opioid consumption and improving postoperative sleep quality. Discussion. Perioperative dexmedetomidine has limited analgesic benefits in lateral thoracotomy for esophageal cancer when added to an opioid-based multimodal anesthetic regimen but can reduce opioid consumption.

Toxoplasma gondii is an obligate intracellular parasite responsible for toxoplasmosis, which can cause severe disease in the fetus and immunocompromised individuals. Developing an effective vaccine is crucial to control this disease. Macrophage migration inhibitory factor (MIF) has gained substantial attention as a pivotal upstream cytokine to mediate innate and adaptive immune responses. Homologs of MIF have been discovered in many parasitic species, and one homolog of MIF has been isolated from the parasite Toxoplasma gondii. In this study, the recombinant Toxoplasma gondii MIF (rTgMIF) as a protein vaccine was expressed and evaluated by intramuscular injection in BALB/c mice. We divided the mice into different dose groups of vaccines, and all immunizations with purified rTgMIF protein were performed at 0, 2, and 4 weeks. The protective efficacy of vaccination was analyzed by antibody assays, cytokine measurements and lymphoproliferative assays, respectively. The results obtained indicated that the rTgMIF vaccine elicited strong humoral and cellular immune responses with high levels of IgG antibody and IFN-γ production compared to those of the controls, in addition to slight higher levels of IL-4 production. After vaccination, a stronger lymphoproliferative response was also noted. Additionally, the survival time of mice immunized with rTgMIF was longer than that of the mice in control groups after challenge infection with virulent T. gondii RH tachyzoites. Moreover, the number of brain tissue cysts in vaccinated mice was reduced by 62.26% compared with the control group. These findings demonstrated that recombinant TgMIF protein is a potential candidate for vaccine development against toxoplasmosis.

Objective. To assess different doses of nalbuphine with flurbiprofen compared to sufentanil with flurbiprofen in multimodal analgesia efficacy for elderly patients undergoing gastrointestinal surgery with a transverse abdominis plane block (TAPB). Methods. 158 elderly patients scheduling for elective open gastrointestinal surgery under general anesthesia and TAPB were randomly assigned to four groups according to different doses of nalbuphine with flurbiprofen in postoperative intravenous analgesia (PCIA). Postoperative pain intensity, effective pressing numbers of PCIA, and adverse effects were recorded at 6, 12, 24, and 48 hours after surgery. Results. Postoperative pain intensity, effective pressing numbers, and the incidence of postoperative nausea and vomiting (PONV) were similar among the four groups after surgery, while the severity of PONV was decreased in Group L compared with Group S at 6, 12, and 48 h after surgery. No individual experienced pruritus, respiratory depression, or hypotension. Conclusions. Low dose of nalbuphine (15 μg·kg−1·ml−1) combined with flurbiprofen is superior for elderly patients undergoing elective open gastrointestinal surgery with TAPB in terms of the efficient postoperative analgesia and decreased severity of PONV. This trial is registered with NCT02984865.

Novel stimuli elicit behaviors that are collectively known as specific exploration. These behaviors allow the animal to become more familiar with the novel objects within its environment. Specific exploration is frequently suppressed by defensive reactions to predator cues. Herein, we examine if this suppression occurs in Drosophila melanogaster by measuring the response of these flies to wild harvested predators. The flies used in our experiments have been cultured and had not lived under predator threat for multiple decades. In a circular arena with centrally-caged predators, wild type Drosophila actively avoided the pantropical jumping spider, Plexippus paykulli, and the Texas unicorn mantis, Phyllovates chlorophaena, indicating an innate defensive reaction to these predators. Interestingly, wild type Drosophila males also avoided a centrally-caged mock spider, and the avoidance of the mock spider became exaggerated when it was made to move within the cage. Visually impaired Drosophila failed to detect and avoid the Plexippus paykulli and the moving mock spider, while the broadly anosmic orco2 mutants were fully capable of detecting and avoiding Plexippus paykulli, indicating that these flies principally relied upon vison to perceive the predator stimuli. During early exploration of the arena, exploratory activity increased in the presence of Plexippus paykulli and the moving mock spider. The elevated activity induced by Plexippus paykulli disappeared after the fly had finished exploring, suggesting the flies were capable of habituating the predator cues. Taken together, these results indicate that despite being isolated from predators for decades Drosophila will visually detect these predators, retain innate defensive behaviors, respond by increasing exploratory activity in the arena rather than suppressing activity, and may habituate to normal predator cues.

Antisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach to antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc to the 5′-terminus of the ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase techniques. Here we show a direct comparison of a solution-phase and a solid-phase conjugation strategy. The solution-phase approach, using amine-pentafluorophenyl (PFP) ester coupling, is higher yielding and gives material of slightly higher purity, but requires several additional unit operations and longer production time. The solid-phase approach, using a protected GalNAc ligand phosphoramidite, is more expedient, but results in lower yield and purity. Both strategies efficiently deliver conjugated material in excellent purity.

Introduction: Music interventions can alleviate patient anxiety and improve post-surgical satisfaction. However, it remains uncertain whether personal music preferences affect efficacy. The authors tested whether personal music intervention with patient-selected songs played ad libitum is more effective than standard therapist-designed treatment with classical music. Methods: A prospective, parallel-group, single-blinded, randomized controlled trial with 229 participants (aged 18-60 years) previously scheduled for elective surgery. Data analyses followed a modified intention-to-treat principle. The patients were randomized into three groups: Standard care without music (Control), therapist-designed classic music treatment (TT), or personal music intervention with patient-selected songs played ad libitum by the patient (PI). All patients received standard post-anaesthesia care, and music intervention was started upon arrival at the post-anaesthesia care unit. Primary outcomes were anxiety and overall satisfaction at discharge. In contrast, secondary outcomes were systolic blood pressure during music intervention, the sleep quality of the night after surgery, and the occurrence of postoperative nausea and vomiting within the first 24 h after surgery. Results: Compared with therapist-designed music treatment, personal intervention decreased systolic blood pressure (T0: 124.3 ± 13.7, 95% CI:121-127.7; T20min: 117.6 ± 10.4, 95% CI:115-120.1; T30min: 116.9 ± 10.6, 95% CI:114.3-119.4), prevented postoperative nausea and vomiting (Control: 55.9%, TT: 64.6%, PI: 77.6%), including severe postoperative nausea (VAS score>4; Control: 44.1%; TT: 33.8%; PI: 20.9%) and severe emesis (Frequency = 3, Control: 13.2%; TT: 7.7%; PI: 4.5%). None of the treatments affected sleep quality at night after surgery (Median, Q1-Q3, Control: 3, 1-3; TT: 3, 1-4; PI: 3, 1-3.5). Personal, but not therapist, music intervention significantly prevented anxiety (Control: 36.4 ± 5.9, 95% CI:35.0-37.9; TT: 36.2 ± 7.1, 95% CI: 34.4-37.9; PI: 33.8 ± 5.6, 95% CI: 32.4-35.2) and emesis (Control: 23.9%; TT: 23.4%; PI: 13.2%) and improved patient satisfaction (Median, Q1-Q3, C: 8, 6-8; TT: 8, 7-9; PI: 8, 7-9). Conclusions: Personal music intervention improved postoperative systolic blood pressure, anxiety, nausea, emesis, and overall satisfaction, but not sleep quality, as compared to therapist-designed classic intervention. [ABSTRACT FROM AUTHOR]