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Background: The safety and efficacy of robotic liver resection (RLR) for patients with hepatocellular carcinoma (HCC) have been reported worldwide. However, the exact role of RLR in HCC patients with liver cirrhosis is not sufficiently determined., Methods: We conducted a retrospective study on consecutive patients with cirrhosis or non-cirrhosis who received RLR for HCC from 2018 to 2023. Data on patients' demographics and perioperative outcomes were collected and analyzed. Propensity score matching (PSM) analysis was performed. Multivariate logistic regression analysis was performed to determine the risk factors of prolonged postoperative length of stay (LOS) and morbidity., Results: Of the 571 patients included, 364 (64%) had cirrhosis. Among the cirrhotic patients, 48 (13%) were classified as Child-Pugh B. After PSM, the cirrhosis and non-cirrhosis group (n = 183) had similar operative time, estimated blood loss, postoperative blood transfusion, LOS, overall morbidity (p > 0.05). In addition, the intraoperative and postoperative outcomes were similar between the two groups in the subgroup analyses of patients with tumor size ≥ 5 cm, major hepatectomy, and high/expert IWATE difficulty grade. However, patients with Child-Pugh B cirrhosis had longer LOS and more overall morbidity than that of Child-Pugh A. Child-Pugh B cirrhosis, ASA score > 2, longer operative time, and multiple tumors were risk factors of prolonged LOS or morbidity in patients with cirrhosis., Conclusion: The presence of Child-Pugh A cirrhosis didn't significantly influence the difficulty and perioperative outcomes of RLR for selected patients with HCC. However, even in high-volume center, Child-Pugh B cirrhosis was a risk factor for poor postoperative outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Naphthalene (NAP) was frequently detected in polycyclic aromatic hydrocarbons (PAHs)-contaminated soil, and its residues may pose an eco-toxicological threat to soil organisms. The toxic effects of NAP were closely tied to phenolic and quinone metabolites in biological metabolism. However, the present knowledge concerning the eco-toxicological impacts of NAP metabolites at the animal level is scanty. Here, we assessed the differences in the eco-toxicological responses of Eisenia fetida (E. fetida) in NAP, 1-naphthol (1-NAO) or 1,4-naphthoquinone (1,4-NQ) contaminated soils. NAP, 1-NAO, and 1,4-NQ exposure triggered the onset of oxidative stress as evidenced by the destruction of the antioxidant enzyme system. The lipid peroxidation and DNA oxidative damage levels induced by 1-NAO and 1,4-NQ were higher than those of NAP. The elevation of DNA damage varied considerably depending on differences in oxidative stress and the direct mode of action of NAP or its metabolites with DNA. All three toxicants induced different degrees of physiological damage to the body wall, but only 1, 4-NQ caused the shedding of intestinal epithelial cells. The integrated biomarker response for different exposure times illustrated that the comprehensive toxicity at the animal level was 1,4-NQ > 1-NAO > NAP, and the time-dependent trends of oxidative stress responses induced by the three toxicants were similar. At the initial stage, the antioxidant system of E. fetida responded positively to the provocation, but the ability of E. fetida to resist stimulation decreased with the prolongation of time resulting in provocation oxidative damage. This study would provide new insights into the toxicological effects and biohazard of PAHs on soil animals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The human equilibrative nucleoside transporter 1 (SLC29A1, hENT1) is a solute carrier that modulates the passive transport of nucleosides and nucleobases, such as adenosine. This nucleoside regulates various physiological processes, such as vasodilation and -constriction, neurotransmission and immune defense. Marketed drugs such as dilazep and dipyridamole have proven useful in cardiovascular afflictions, but the application of hENT1 inhibitors can be beneficial in a number of other diseases. In this study, 39 derivatives of dilazep's close analogue ST7092 were designed, synthesized and subsequently assessed using [ 3 H]NBTI displacement assays and molecular docking. Different substitution patterns of the trimethoxy benzoates of ST7092 reduced interactions within the binding pocket, resulting in diminished hENT1 affinity. Conversely, [ 3 H]NBTI displacement by potentially covalent compounds 14b, 14c, and 14d resulted in high affinities (K i values between 1.1 and 17.5 nM) for the transporter, primarily by the ability of accommodating the inhibitors in various ways in the binding pocket. However, any indication of covalent binding with amino acid residue C439 remained absent, conceivably as a result of decreased nucleophilic residue reactivity. In conclusion, this research introduces novel dilazep derivatives that are active as hENT1 inhibitors, along with the first high affinity dilazep derivatives equipped with an electrophilic warhead. These findings will aid the rational and structure-based development of novel hENT1 inhibitors and pharmacological tools to study hENT1's function, binding mechanisms, and its relevance in (patho)physiological conditions., (© 2024. The Author(s).)

The Electrolytic Manganese Residue (EMR) is a by-product of the electrolytic manganese metal (EMM) industry, containing high concentrations of potential pollutants such as NH 4 + -N and soluble Mn 2+ . These components pose a serious threat to the ecological environment. To explore accurate, efficient, and harmless treatment methods for EMR, this study proposes a low-temperature thermochemical approach. The orthogonal experiment design investigates the effects of reaction temperature, reaction time, quicklime (CaO), sodium carbonate (Na 2 CO 3 ), sodium phosphate (Na 3 PO 4 ) (Reviewer #3), and water consumption on manganese solidified and ammonia removal from EMR. The results indicate that optimal conditions are a reaction temperature of 60 ℃ (Reviewer #3) and a reaction time of 10 min. CaO precipitates Mn 2+ as manganese hydroxide (Mn(OH) 2 ) (Reviewer #3), achieving effective manganese solidified and ammonia removal. The addition of Na 2 CO 3 causes Mn 2+ to form manganesecarbonate (MnCO 3 ) (Reviewer #3)precipitate, while Na 3 PO 4 makes Mn 2+ form Manganese phosphate trihydrate (Mn 3 (PO 4 ) 2 ·3H 2 O) (Reviewer #3). Increased water consumption enhances the interaction adequacy between ions. Under optimal conditions (CaO 10%, Na 2 CO 3 1%, Na 3 PO 4 0.5%, and 80% water consumption), the removal rate of ammonium ions reaches 98.5%, and the solidification rate of soluble Mn 2+ is 99.9%. The order of influence on ammonium ion removal is CaO > water consumption > Na 3 PO 4  > Na 2 CO 3 . Therefore, this study provides a new method for low-cost process disposal and efficient harmless treatment of EMR (Reviewer #3)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this meta-analysis was to evaluate the efficacy and safety of robotic pancreaticoduodenectomy (RPD) in improving perioperative aspects and postoperative complications in patients., Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library database systems for studies that compared RPD with laparoscopic pancreaticoduodenectomy (LPD). Meta-analysis was performed for 24 relevant outcomes, including perioperative outcomes and postoperative complications. Subsequently, a subgroup analysis based on geographical regions was conducted to investigate the impact of regional differences on the perioperative outcomes of the RPD group and the LPD group., Results: This review found 19 studies with 12,731 individuals (3539 RPD and 9192 LPD). In comparison to LPD, RPD had lower rates of Conversion (OR = 0.58, P < 0.00001), Blood Transfusion (OR = 0.59, P = 0.02), Length of Stay (MD = - 0.54, P = 0.01), postoperative complications [Pneumonia (OR = 0.31, P < 0.0001), and Wound Disruption (OR = 0.26, P = 0.0007)], and more thorough lymph node harvesting (MD = 1.25, P = 0.001). Subgroup analysis showed that Blood Transfusion (I 2  = 55%, P = 0.02), Conversion (I 2  = 30%, P < 0.00001), Length of Stay (I 2  = 71%, P = 0.01), and Lymph Node Harvested (I 2  = 87%, P = 0.001) were statistically significant. Interestingly, compared to China, other countries had lower rates of Conversion and more lymph nodes harvested for RPD surgery., Conclusion: The benefits of RPD surgery over LPD surgery in terms of therapy and an optimistic short-term prognosis are clearly supported by this study. Moreover, subgroup analysis based on regional differences revealed statistically significant results for Conversion, Length of Stay (days), Number of Lymph Nodes Harvested and the rate of Blood Transfusion, indicating significant variability across regions. This study provides a solid theoretical foundation and basis for the advancement of RPD in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes., Methods: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors., Results: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates., Conclusions: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes., (© 2024. Society of Surgical Oncology.)

Sinoatrial node (SAN) is the pacemaker of the heart in charge of initiating spontaneous electronical activity and controlling heart rate. Myocytes from SAN can generate spontaneous rhythmic action potentials, which propagate through the myocardium, thereby triggering cardiac myocyte contraction. Acutely, the method for isolating sinoatrial node myocytes (SAMs) is critical in studying the protein expression and function of myocytes in SAN. Currently, the SAMs were isolated by transferring SAN tissue directly into the digestion solution, but it is difficult to judge the degree of digestion, and the system was unstable. Here, we present a modified protocol for the isolation of SAMs in mice, based on the collagenase II and protease perfusion of the heart using a Langendorff apparatus and subsequent dissociation of SAMs. The appearance and droplet flow rate of the heart could be significantly changed during enzymatic digestion via perfusion, which allowed us to easily judge the degree of digestion and avoid incomplete or excessive digestion. The SAMs with stable yield and viability achieved from our optimized approach would facilitate the follow-up experiments., (© 2024. The Society for In Vitro Biology.)

Microplastics (MPs) have attracted much attention in recent years, due to the difficulty of degradation and threats to ecological systems and humans. Based on the analysis of 1429 articles on MPs in soil, we found that we know little about the behavior and fate of manure-born MPs from the livestock and poultry production systems to agriculture soils. This review summarizes the analytical methods for sampling, separation, and identification and the occurrence of MPs in livestock and poultry manure, mainly based on 7 surveys related to manure-born MPs. Then, the sources, fate, and environmental risks of MPs in livestock and poultry manure are discussed. MPs, heavy metals, pathogens, antibiotic resistance genes, and persistent organic pollutants are common pollutants in livestock and poultry manure. Worse, manure-born MPs will become smaller, rougher, and more numerous and could easily form more toxic compound pollution after complicated processes of manure treatment, which seriously threatens agricultural soil safety. Finally, an outlook is offered for future research. We hope this article to attract attention to the risks of MPs in livestock and poultry manure and provide a reference for future research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10 -5 mol/m 3 and 6.37×10 -6 mol/m 3 . In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations., (© 2023. Controlled Release Society.)

Background: Accumulating evidences have stressed the association between hypoxanthine phosphoribosyl transferase 1 (HPRT1) overexpression and the poor prognosis of various cancers. Our study, herein, preliminarily investigates the involvement of HPRT1 in nasopharyngeal carcinoma (NPC)., Methods: Data from TCGA were applied to read HPRT1 expression in diverse cancers including NPC and to predict the prognosis of NPC patients. The total RNA and protein from NPC cells and nasopharyngeal epithelial cells NP460 were extracted to quantify HPRT1 expression. Following the completion of transfection, the proliferation and migration of NPC cells were determined employing MTT, colony formation and western blot assay (the quantification on expressions of protein related to proliferation and migration)., Results: HPRT1 was differentially expressed in diverse cancers yet particularly highly expressed in NPC, and high HPRT1 expression was related to the poor prognosis of NPC patients. Also, HPRT1 expression was higher in NPC cells and its silencing diminished the viability and proliferation of NPC cells and reduced the expressions of CyclinD1, CyclinE, Multidrug Resistance Protein 1 (MDR1), matrix metalloproteinase (MMP)-2, and MMP-9., Conclusion: This study preliminarily explored the involvement of HPRT1 in NPC based on some cellular assays in vitro, which may provide evidence for investigating the specific mechanism underlying the effects of HPRT1 in cancers., (© 2024. The Author(s).)

Background: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated., Methods: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out., Results: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells., Conclusions: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The relation between operative time and postoperative complications in liver surgery is unclear. The aim of this study is to assess the impact of operative time on the development of postoperative complications in patients who underwent minimally invasive or open liver resections of various anatomical extent and technical difficulty levels., Methods: In this retrospective cohort study, patients that underwent a right hemihepatectomy (RH), technically major resection (anatomically minor resection in segment 1, 4a, 7 or 8; TMR) or left lateral sectionectomy (LLS) between 2000 and 2022 were extracted from a multicenter database comprising the prospectively maintained databases of 31 centers in 13 countries. Minimally invasive procedures performed during the learning curve were omitted. Logistic regression models, performed separately for 9 different groups based on stratification by procedure type and allocated surgical approach, were used to assess the association between the fourth quartile of operative time (25% of patients with the longest operative time) and postoperative complications., Results: Overall, 5424 patients were included: 1351 underwent RH (865 open, 373 laparoscopic and 113 robotic), 2821 TMR (1398 open, 1225 laparoscopic and 198 robotic), and 1252 LLS (241 open, 822 laparoscopic and 189 robotic). After adjusting for potential confounders (age, BMI, gender, ASA grade, previous abdominal surgery, disease type and extent, blood loss, Pringle, intraoperative transfusions and incidents), the fourth quartile of operative time, compared to the first three quartiles, was associated with an increased risk of postoperative complications after open, laparoscopic and robotic TMR (aOR 1.35, p = 0.031; aOR 1.74, p = 0.001 and aOR 3.11, p = 0.014, respectively), laparoscopic and robotic RH (aOR 1.98, p = 0.018 and aOR 3.28, p = 0.055, respectively) and solely laparoscopic LLS (aOR 1.69, p = 0.019)., Conclusions: A prolonged operative time is associated with an increased risk of postoperative complications, although it remains to be defined if this is a causal relationship., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibroblastic tumor, characterized to be an aggressive disease with high frequency of ALK rearrangement, rapid recurrence, and poor prognosis. Primary EIMS of thoracic origin is rarely observed. Herein, we described a case of 28-year-old female developed primary EIMS in the anterior mediastinum with hepatic metastasis. The EIMS displayed sheet-like growth of epithelioid and spindle cells with enlarged nuclei, abundant and eosinophilic cytoplasm, and infiltration of inflammatory cells. Immunohistochemical staining revealed positive expression of ALK in the nuclear membrane, and ALK rearrangement was identified by polymerase chain reaction assay. Alectinib showed partial response, and achieved a meaningful survival benefit for four months. Based on this case report and literature review, ALK inhibitor reveals promising activity on the rare but aggressive EIMS. Awareness of EIMS in thoracic disease and its clinicopathological features is essential to avoid erroneous diagnosis., (© 2024. The Author(s).)

In China, the rate of spicy food consumption is rising, and chili pepper is among the most popular spicy foods consumed nationwide. However, little effort has been made to understand the mechanism behind spicy food craving. This exploratory study aimed to investigate differences in insula-based resting state functional connectivity (rsFC) between spicy food cravers and non-cravers, and the association between rsFC, impulsivity and spicy food craving. A group of extreme cravers (n = 49) and a group of age- and sex-matched non-cravers (n = 46) completed a resting-state fMRI scan, during which participants were instructed to keep their eyes closed, to not think of anything in particular, and to remain awake. Participants completed the Spicy Food Craving Questionnaire, Barratt Impulsiveness Scale, Sensation Seeking Scale and Positive and Negative Affect Schedule, and rated the frequency of spicy food intake. Results revealed increased insula-occipital lobe resting-state functional connectivity in individuals with spicy food cravings, and the positive correlations between insula-middle occipital gyrus rsFC, impulsivity and spicy food craving. Specifically, the insula-middle occipital gyrus rsFC strength mediated the relationship between the motor impulsivity and spicy food craving. It is hoped that our exploratory findings may shed new insights into the neural mechanisms of spicy food craving and motivate further exploration of spicy food craving in diverse contexts and cultures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this paper, we proposed a complete study method to achieve accurate aortic dissection diagnosis at the patient level. Based on the CT angiography (CTA) images, a classification model named DAT-DenseNet, which combined the deep attention Transformer module with the DenseNet architecture is proposed. In the first phase, two DAT-DenseNet are combined in parallel. It is used to accurately achieve two classification task at the CTA images. In the second stage, we propose a feature fusion module. It concatenates and fuses the image features output from the two classification models on a patient by patient basis. In the comparison experiments of classification model performance, DAT-DenseNet obtained 92.41 % accuracy at the image level, which was 2.20 % higher than the commonly used model. In the comparison experiments of model fusion method, our method obtained 90.83 % accuracy at the patient level. The experiments showed that DAT-DenseNet model exhibits high performance at the image level. Our feature fusion module achieves the mapping from two classification image features to patient outcomes. It achieves accurate patient classification. The experiments' results in the Discussion section elaborate the details of the experiment and confirmed that the results were reliable., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) is a prevalent and aggressive malignancy with high mortality rates and significant risks to human well-being. Population-wide screening for tumor suppressor genes and oncogenes shows promise for reducing the incidence and fatality of CRC. Recent studies have suggested that NLRX1, an innate immunity suppressor, may play a role in regulating chronic inflammation and tumorigenesis. However, further investigation is needed to understand the specific role of NLRX1 in CRC. To evaluate the impact of NLRX1 on migration, invasion, and metastasis, two human colon cancer cell lines were studied in vitro. Additionally, a knockout mouse tumor-bearing model was used to validate the inhibitory effect of NLRX1 on tumor emergence and progression. The Seahorse XF96 technology was employed to assess mitochondrial function and glycolysis in colorectal cancer cells overexpressing NLRX1. Moreover, public databases were consulted to analyze gene and protein expression levels of NLRX1. Finally, the results were validated using a series of CRC patient samples. Our findings demonstrate that downregulation of NLRX1 enhances proliferation, colony formation, and tumor-forming capacity in HCT116 and LoVo cells. Conversely, overexpression of NLRX1 negatively impacts basal respiration and mitochondrial ATP-linked respiration in both cell lines, resulting in a notable decrease in maximal respiration during the standard mitochondrial stress test. Furthermore, analysis of data from the TCGA database reveals a significant reduction in NLRX1 expression in colon and rectal cancer tissues compared to normal tissues. This result was validated using clinical samples, where immunohistochemistry staining and western blotting demonstrated a notable reduction in NLRX1 protein levels in CRC compared to adjacent normal tissues. The decreased expression of NLRX1 may serve as a significant prognostic indicator and diagnostic biomarker for CRC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cytokine release syndrome (CRS) is a great challenge for the application of anti-CD19 CAR-T cell therapy. The aim of this study was to investigate the effect of knocking down interferon gamma (IFN-γ) by shRNA as a potential strategy to reduce the cytokine storms. A newly designed short hairpin interference RNA of IFN-γ (shIFN-γ) in CD19CAR gene was constructed. Several cellular model systems of approach using Nalm-6 cell lines including Nalm-6 CD19pos and Nalm-6 CD19neg with or without monocytes and endothelial cells were used to analyze the different levels of cytokines after shIFN-γ-anti-CD19CAR-T cell targeted therapy. The activity of this novel CD19CAR-T was evaluated both in vitro and in NSG mouse model. The killing efficacy of shIFN-γ-anti-CD19CAR-T at the E:T ratio of 2:1 was similar to that of regular anti-CD19CAR-T at the E:T ratio of 1:1. The IFN-γ level in the shIFN-γ-anti-CD19CAR-T cell group was (2673.1 ± 307.4) pg/ml at the E:T ratio of 2:1 which was significantly lower than that ((8261.5 ± 345.5) pg/ml) in the regular anti-CD19CAR-T group at the E:T ratio of 1:1. Cytotoxicity experiments in vitro showed significantly reduced concentrations of IFN-γ, IL-6 and TNFα in the shIFN-γ-anti-CD19CAR-T cell group compared to regular anti-CD19CAR-T cell group. Both regular anti-CD19CAR and shIFN-γ-CD19CAR-T exerted bystander killing effect in vitro. We conclude that shIFN-γ-anti-CD19CAR-T cells can reduce the generation of cytokine storms without significantly compromising their therapeutic efficacy in the preclinical setting. In mouse model, 3 × 10 6 shIFN-γ-anti-CD19CAR-T cells/mouse generated the similar killing efficacy to that with 2 × 10 6 regular anti-CD19CAR-T cells/mouse., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: This study provides novel insights into the evolution, diversification, and functions of melatonin biosynthesis genes in Prunus species, highlighting their potential role in regulating bud dormancy and abiotic stresses. The biosynthesis of melatonin (MEL) in plants is primarily governed by enzymatic reactions involving key enzymes such as serotonin N-acetyltransferase (SNAT), tryptamine 5-hydroxylase (T5H), N-acetylserotonin methyltransferase (ASMT) and tryptophan decarboxylase (TDC). In this study, we analyzed Melatonin genes in four Prunus species such as Prunus avium (Pavi), Prunus pusilliflora (Ppus), Prunus serulata (Pser), and Prunus persica (Pper) based on comparative genomics approach. Among the four Prunus species, a total of 29 TDCs, 998 T5Hs, 16 SNATs, and 115 ASMTs within the genome of four Prunus genomes. A thorough investigation of melatonin-related genes was carried out using systematic biological methods and comparative genomics. Through phylogenetic analysis, orthologous clusters, Go enrichment, syntenic relationship, and gene duplication analysis, we discovered both similarities and variations in Melatonin genes among these Prunus species. Additionally, our study revealed the existence of unique subgroup members in the Melatonin genes of these species, which were distinct from those found in Arabidopsis genes. Furthermore, the transcriptomic expression analysis revealed the potential significance of melatonin genes in bud dormancy regulation and abiotic stresses. Our extensive results offer valuable perspectives on the evolutionary patterns, intricate expansion, and functions of PavMEL genes. Given their promising attributes, PavTDCs, PavT5H, PavNAT, and three PavASMT genes warrant in-depth exploration as prime candidates for manipulating dormancy in sweet cherry. This was done to lay the foundation for future explorations into the structural and functional aspects of these factors in Prunus species. This study offers significant insights into the functions of ASMT, SNAT, T5H, and TDC genes and sheds light on their roles in Prunus avium. Moreover, it established a robust foundation for further exploration functional characterization of melatonin genes in fruit species., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Robotic distal pancreatectomy has increasingly been accepted as it has overcome some of the limitations of open distal pancreatectomy, whilst the outcomes following robotic radical antegrade modular pancreatosplenectomy (RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of robotic RAMPS and open RAMPS for PDAC., Methods: The patients who underwent robotic RAMPS and open RAMPS for PDAC at our clinical centre between January 2017 and December 2021 were reviewed. After a propensity score matching (PSM) at a 1:1 ratio, the perioperative and pathological outcomes in the both groups were reviewed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients., Results: 318 cases were recorded in robotic and open groups. The robotic group showed advantages in operative time [205.00 (166.00, 240.00) min vs 235 (184.75, 270.00) min, P = 0.002], estimated blood loss [100 (50, 100) ml vs 300 (100, 400) ml, P < 0.001], delayed gastric emptying [0 vs 5.03%, P = 0.007] and postoperative hospital stay [7.00 (5.00, 10.00) days vs 11.00 (8.00, 14.00) days, P < 0.001]. There were no significant differences in rate of severe postoperative complications between the robotic group and the open group. Multivariable analysis showed that carbohydrate antigen 19-9, estimated blood loss, N stage, tumour differentiation, chemotherapy and vascular invasion were independent risk factors for OS and RFS of these patients., Conclusions: Robotic RAMPS was safe and had some advantages over open RAMPS for PDAC. There were no significantly differences in oncological outcomes and long-term survival rates between the robotic and open groups. Robotic RAMPS expanded the indications for minimally invasive surgeries for PDAC to a certain extent., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The relationships between sleep quality and sleep hygiene awareness in the Chinese population were unclear. We aimed to investigate the associations and related factors between sleep quality and sleep hygiene awareness in adults and to identify the most central domain for sleep quality using network analysis., Methods: A cross-sectional survey was conducted from April 22 to May 5, 2020. Adults (18 years old or above) who had access to smartphones were invited to participate in this survey. The Pittsburg Sleep Quality Index (PSQI) and the Sleep Hygiene Awareness and Practice Scale (SHAPS) were used to evaluate the sleep quality and sleep hygiene awareness of the participants. Propensity score matching (PSM) was used as sensitivity analysis to reduce the confounding effects. Multiple logistic regression was performed to evaluate the associations. The R packages "bootnet" and "qgraph" were used to estimate the connection and calculate the network centrality indices between good and poor sleepers., Results: In total, 939 respondents were included in the analysis. Of them, 48.8% (95% CI: 45.6-52.0%) were identified as poor sleepers. Participants with nervous system diseases, psychiatric diseases, and psychological problems were more likely to have poor sleep quality. The notion that using sleep medication regularly was beneficial to sleep was associated with poor sleep quality. Similarly, the notion that waking up at the same time each day disrupted sleep was also associated with poor sleep quality. The findings were consistent before and after PSM. Subjective sleep quality was the most central domain for sleep quality in good and poor sleepers., Conclusion: Poor sleep quality was positively associated with certain sleep hygiene notions in Chinese adults. Effective measures such as self-relief, sleep hygiene education, and cognitive behavioral treatment may have been needed to improve sleep quality, especially during the COVID-19 outbreak., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

As an important raw material and intermediate product of the petrochemical industry, fluoranthene (Fla) can be emitted with industrial activities and has become a typical polycyclic aromatic hydrocarbon enriched in the Chinese topsoil layer, posing a significant threat to sensitive soil biota. Here, multispectral tools and molecular simulation techniques were integrated to elucidate the molecular mechanism of Fla interaction with key antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) at the molecular level. Meanwhile, we further revealed the cellular responses of SOD and CAT and the associated redox states in earthworm (Eisenia fetida) coelomocytes based on the molecular-level results. Our results showed that the exposure to Fla affected the backbone structure of SOD and CAT molecules and resulted in the formation of Fla-SOD polymers as well as an overall reduction in the size of the Fla-CAT binding system. Fla altered the microenvironment around Tyr residues in the SOD molecule and quenched the endogenous fluorescence of Tyr within the CAT molecule. In earthworm coelomocytes, Fla at 60 and 80 μM resulted in a significant elevation of CAT and SOD activities by 114% (p = 0.032) and 6.09% (p = 0.013), respectively. Molecular simulation results suggested that Fla-induced changes in the structure and conformation of SOD and CAT may be the key reason for their altered activities. The related redox homeostasis detection in earthworm coelomocytes indicated that high concentrations (80 μM) of Fla led to a significant accumulation of intracellular ROS (p = 0.018) and resulted in the development of lipid peroxidation. Our work contributes to an in-depth understanding of the biological effect of Fla to sensitive soil fauna, thus providing new ideas for Fla ecological risk prevention and control., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transient ischemic attack (TIA) presents a high risk for subsequent stroke, Alzheimer's disease (AD), and related dementia (ADRD). However, the neuropathophysiology of TIA has been rarely studied. By evaluating recurrent TIA-induced neuropathological changes, our study aimed to explore the potential mechanisms underlying the contribution of TIA to ADRD. In the current study, we established a recurrent TIA model by three times 10-min middle cerebral artery occlusion within a week in rat. Neither permanent neurological deficit nor apoptosis was observed following recurrent TIA. No increase of AD-related biomarkers was indicated after TIA, including increase of tau hyperphosphorylation and β-site APP cleaving enzyme 1 (BACE1). Neuronal cytoskeleton modification and neuroinflammation was found at 1, 3, and 7 days after recurrent TIA, evidenced by the reduction of microtubule-associated protein 2 (MAP2), elevation of neurofilament-light chain (NFL), and increase of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia at the TIA-affected cerebral cortex and basal ganglion. Similar NFL, GFAP and Iba1 alteration was found in the white matter of corpus callosum. In summary, the current study demonstrated that recurrent TIA may trigger neuronal cytoskeleton change, astrogliosis, and microgliosis without induction of cell death at the acute and subacute stage. Our study indicates that TIA-induced neuronal cytoskeleton modification and neuroinflammation may be involved in the vascular contribution to cognitive impairment and dementia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ureteral DJ stents are commonly used devices in urology. However, stent placement may cause LUTS and affect the quality of life. We evaluated the direct relationship between ureteral stents and sexual function., Methods: From October 2022 to December 2023, 82 male and 90 female sexually active patients who underwent ureteroscopy at Beijing Tiantan Hospital, Capital Medical University, were enrolled. The basic information, surgical data, and two questionnaire data including the International Index of Erectile Function-5 and the Female Sexual Function Index of patients before the operation (baseline, T0), on the day of the ureteral DJ tube extraction (T1), and 4 weeks after ureteral DJ tube extraction (T2) were collected to analyze the changes in the patients' sexual function., Results: The average age of male patients was 36 years and of female patients 39 years. Before the ureteral DJ stent placement, the mean ± SD IIEF-5 score was 22.86 ± 0.91, and the average FSFI score was 31.66 ± 1.44. On the day of the ureteral DJ stent removal, the IIEF-5 score was 16.37 ± 2.62 (p < 0.01) and the FSFI score was 15.83 ± 4.05 (p < 0.01). Four weeks after ureteral DJ stent removal, the average IIEF-5 score was 22.77 ± 1.06 (p = 0.61) and the average FSFI score was 30.99 ± 1.79 (p = 0.78)., Conclusions: Indwelling ureteral stents after ureteroscopy can temporarily affect the sexual function of both male and female patients, typically recovering within 4 weeks after stent removal., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions., (© 2024. The Author(s).)

Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca 2+ , Fe 3+ , Cu 2+ and Zn 2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. HIGHLIGHTS: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, characterized by high rates of angiogenesis and immune evasion. Paraspeckle genes, involved in gene regulation and RNA metabolism, have recently been linked to tumor progression. This study aims to elucidate the relationship between paraspeckle genes and HCC prognosis, focusing on SFPQ, DDX39B, and UBAP2., Methods: We analyzed HCC (LIHC) and prostate cancer (PRAD) samples from the TCGA database to explore the correlation between paraspeckle genes and angiogenesis. We conducted unsupervised clustering, risk scoring, and survival analysis to identify distinct patient groups and their clinical outcomes. Gene expression data were used to perform differential analysis and Gene Ontology (GO) enrichment., Results: Our analysis identified significant correlations between paraspeckle genes and angiogenesis across multiple cancer types. Elevated expression levels of SFPQ, DDX39B, and UBAP2 were associated with poor prognosis in HCC patients, and all of them has statistical significance. Unsupervised clustering of HCC samples based on paraspeckle gene expression revealed two distinct clusters, with high-risk patients exhibiting stronger immune suppression and tumor immune evasion. GO enrichment highlighted critical pathways related to angiogenesis and immune regulation. Additionally, a risk scoring model based on these genes effectively distinguished high-risk and low-risk patient groups, providing valuable prognostic insights., Conclusion: This study demonstrates that SFPQ, DDX39B, and UBAP2 are significantly associated with poor prognosis in HCC, likely due to their roles in promoting angiogenesis and immune suppression. These findings highlight the potential of paraspeckle genes as prognostic biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in HCC. Further research into their functional mechanisms and clinical applicability is crucial for advancing HCC treatment and improving patient outcomes., (© 2024. The Author(s).)

Background: We aimed to explore the association of sleep duration with depressive symptoms among rural-dwelling older adults in China, and to estimate the impact of substituting sleep with sedentary behavior (SB) and physical activity (PA) on the association with depressive symptoms., Methods: This population-based cross-sectional study included 2001 rural-dwelling older adults (age ≥ 60 years, 59.2% female). Sleep duration was assessed using the Pittsburgh Sleep Quality Index. We used accelerometers to assess SB and PA, and the 15-item Geriatric Depression Scale to assess depressive symptoms. Data were analyzed using restricted cubic splines, compositional logistic regression, and isotemporal substitution models., Results: Restricted cubic spline curves showed a U-shaped association between daily sleep duration and the likelihood of depressive symptoms (P-nonlinear < 0.001). Among older adults with sleep duration < 7 h/day, reallocating 60 min/day spent on SB and PA to sleep were associated with multivariable-adjusted odds ratio (OR) of 0.81 (95% confidence interval [CI] = 0.78-0.84) and 0.79 (0.76-0.82), respectively, for depressive symptoms. Among older adults with sleep duration ≥ 7 h/day, reallocating 60 min/day spent in sleep to SB and PA, and reallocating 60 min/day spent on SB to PA were associated with multivariable-adjusted OR of 0.78 (0.74-0.84), 0.73 (0.69-0.78), and 0.94 (0.92-0.96), respectively, for depressive symptoms., Conclusions: Our study reveals a U-shaped association of sleep duration with depressive symptoms in rural older adults and further shows that replacing SB and PA with sleep or vice versa is associated with reduced likelihoods of depressive symptoms depending on sleep duration., (© 2024. The Author(s).)

Background: Unlike human epidermal growth factor receptor 2 (HER2) amplification or exon 20 insertions, missense mutations in the extracellular domain (ECD), transmembrane domain (TMD), and intracellular domain (ICD) of the HER2 protein have been implicated as oncogenic in non-small cell lung cancer (NSCLC). However, their molecular subtypes, structural disparities, and clinical responses to current medical treatments, particularly HER2-targeted tyrosine kinase inhibitors (TKIs), remain unclear in NSCLC and warrant investigation., Methods: A real-world observational ATLAS study was conducted to gather and analyze therapeutic outcomes of chemotherapy or TKIs for heterogeneous HER2 missense mutations in NSCLC. Computational models of typical ECD, TMD, and ICD mutations were utilized to explore their structural variances., Results: We screened 37 eligible patients with HER2-activating missense mutations, of which 35 patients who had received chemotherapy or HER2-targeted TKIs as first-line therapy were available for response assessment. The median progression-free survival (PFS) for chemotherapy was 4.43 months (95% confidence interval [CI], 3.77-5.10), with an objective response rate (ORR) of 26.1% (6/23) and a disease control rate (DCR) of 17/23 (73.9%). The administration of afatinib, dacomitinib, and pyrotinib, HER2-targeted TKIs, achieved a median PFS of 4.65 months, with an ORR of 33.3% (4/12) and a DCR of 83.3% (10/12). Molecular modeling and computational simulations of ECD, TMD, and ICD mutations revealed their distinct structural characteristics., Conclusion: In comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC., (© 2024. The Author(s).)

A Gram-staining-negative, facultative aerobic, motile strain, designated strain ZSDE20 T , was isolated from the surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA gene of strain ZSDE20 T , affiliated it to the genus Photobacterium. It was closely related to Photobacterium lutimaris DF-42  T (98.92% 16S rRNA gene sequence similarity). Growth occurred at 4-28ºC (optimum 28ºC), pH 1.0-7.0 (optimum 7.0) and in the presence of 1-7% (w/v) NaCl (optimum 3%). The dominant fatty acids were summed feature 3 (C16:1 ω7c or/and C16:1 ω6c, 34.23%), summed feature 8 (C18:1 ω7c and C18:1 ω6c, 10.36%) and C16:0 (20.05%). The polar lipids of strain ZSDE20 T comprised phosphatidylethanolamine, phosphatidylcholine, lyso-phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol dimannoside, phosphatidylinositol mannosides and two unknown lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The DNA G + C content of strain ZSDE20 T was 45.6 mol%. Average nucleotide identity (ANI) values between ZSDE20 T and its reference species were lower than the threshold for species delineation (95-96%); in silico DNA-DNA hybridization further showed that strain ZSDE20 T had less than 70% similarity to its relatives. Based on the polyphasic evidences, strain ZSDE20 T is proposed as representing a novel species of the genus Photobacterium, for which the name Photobacterium pectinilyticum sp. nov. is proposed. The type strain is ZSDE20 T (= MCCC 1K06283 T  = KCTC 82885  T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Lumbar disc herniation is one of the most prevalent orthopedic issues in clinical practice. The lumbar spine is a crucial joint for movement and weight-bearing, so back pain can significantly impact the everyday lives of patients and is prone to recurring. The pathogenesis of lumbar disc herniation is complex and diverse, making it difficult to identify and assess after it has occurred. Magnetic resonance imaging (MRI) is the most effective method for detecting injuries, requiring continuous examination by medical experts to determine the extent of the injury. However, the continuous examination process is time-consuming and susceptible to errors. This study proposes an enhanced model, BE-YOLOv5, for hierarchical detection of lumbar disc herniation from MRI images. To tailor the training of the model to the job requirements, a specialized dataset was created. The data was cleaned and improved before the final calibration. A final training set of 2083 data points and a test set of 100 data points were obtained. The YOLOv5 model was enhanced by integrating the attention mechanism module, ECAnet, with a 3 × 3 convolutional kernel size, substituting its feature extraction network with a BiFPN, and implementing structural system pruning. The model achieved an 89.7% mean average precision (mAP) and 48.7 frames per second (FPS) on the test set. In comparison to Faster R-CNN, original YOLOv5, and the latest YOLOv8, this model performs better in terms of both accuracy and speed for the detection and grading of lumbar disc herniation from MRI, validating the effectiveness of multiple enhancement methods. The proposed model is expected to be used for diagnosing lumbar disc herniation from MRI images and to demonstrate efficient and high-precision performance., (© 2024. International Federation for Medical and Biological Engineering.)

Copper ions (Cu 2+ ) and sulfide (S 2- ) play essential roles in many physiologies and pathologic processes. Herein, a new "on-off-on" tryptanthrin-based probe TR-1 (TR-1) has been designed and synthesized in a facile and economical way. TR-1 exhibited highly selective and sensitive response to Cu 2+ without any interference over 14 competitive metal ions and the detection limit downs to 24 nM, which is far below the Chinese standard of fishery water quality (157 nM). The 'in situ' prepared complex TR-1 + Cu 2+ could also be applied to detect S 2- with the detection limit of 62 nM. Further, TR-1 was potentially applied for the analysis of copper ions in water samples., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Nickel-rich layered oxide LiNi x Co y Mn z O 2 (NCM, x + y + z = 1) is the most promising cathode material for high-energy lithium-ion batteries. However, conventional synthesis methods are limited by the slow heating rate, sluggish reaction dynamics, high energy consumption, and long reaction time. To overcome these challenges, we first employed a high-temperature shock (HTS) strategy for fast synthesis of the NCM, and the approaching ultimate reaction rate of solid phase transition is deeply investigated for the first time. In the HTS process, ultrafast average reaction rate of phase transition from Ni 0.6 Co 0.2 Mn 0.2 (OH) 2 to Li- containing oxides is 66.7 (% s -1 ), that is, taking only 1.5 s. An ultrahigh heating rate leads to fast reaction kinetics, which induces the rapid phase transition of NCM cathodes. The HTS-synthesized nickel-rich layered oxides perform good cycling performances (94% for NCM523, 94% for NCM622, and 80% for NCM811 after 200 cycles at 4.3 V). These findings might also assist to pave the way for preparing effectively Ni-rich layered oxides for lithium-ion batteries., (© 2024. The Author(s).)

Tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) is increasing and has emerged as a global public health issue. However, the mechanism of tigecycline resistance remains unclear. The objective of this study was to investigate the potential role of efflux pump system in tigecycline resistance. 29 tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains were collected and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The ramR, acrR, rpsJ, tet(A), and tet(X) were amplified by polymerase chain reaction (PCR). The mRNA expression of different efflux pump genes and regulator genes were analyzed by real-time PCR. Additionally, KP14 was selected for genome sequencing. KP14 genes without acrB, oqxB, and TetA were modified using suicide plasmids and MIC of tigecycline of KP14 with target genes knocked out was investigated. It was found that MIC of tigecycline of 20 out of the 29 TNSKP strains decreased by over four folds once combined with phenyl-arginine-β-naphthylamide dihydrochloride (PaβN). Most strains exhibited upregulation of AcrAB and oqxAB efflux pumps. The strains with acrB, oqxB, and tetA genes knocked out were constructed, wherein the MIC of tigecycline of KP14∆acrB and KP14∆tetA was observed to be 2 µg/mL (decreased by 16 folds), the MIC of tigecycline of KP14ΔacrBΔTetA was 0.25 µg/mL (decreased by 128 folds), but the MIC of tigecycline of KP14∆oqxB remained unchanged at 32 µg/mL. The majority of TNSKP strains demonstrated increased expression of AcrAB-TolC and oqxAB, while certain strains showed mutations in other genes associated with tigecycline resistance. In KP14, both overexpression of AcrAB-TolC and tet(A) gene mutation contributed to the mechanism of tigecycline resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors., Aim: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system., Method: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model., Results: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings., Conclusion: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The blood-brain barrier (BBB) poses a major obstacle in the treatment of all types of central nervous system (CNS) diseases. Small interfering RNA (siRNA) offers in principle a promising therapeutic approach by downregulating disease-related genes via RNA interference. However, the BBB is a formidable barrier for macromolecules such as nucleic acids. In an effort to develop a brain-targeted strategy for siRNA delivery systems formed by electrostatic interactions with cationic polymers (polyplexes (PXs)), we investigated the suitability of the well-known surfactant-based approach for Apolipoprotein E (ApoE)-functionalization of nanoparticles (NPs). The aim of this present work was to investigate if ApoE coating of siRNA PXs formed with cationic branched 25-kDa poly(ethyleneimine) (b-PEI) and nylon-3 polymers without or after precoating with polysorbate 80 (PS 80) would promote successful delivery across the BBB. We utilized highly hydrophobic NM 0.2 /CP 0.8 nylon-3 polymers to evaluate the effects of hydrophobic cyclopentyl (CP) subunits on ApoE binding efficacy and observed successful ApoE binding with and without PS 80 precoating to the nylon-3 but not the PEI polyplexes. Accordingly, ApoE-coated nylon-3 polyplexes showed significantly increased uptake and gene silencing in U87 glioma cells but no benefit in vivo. In conclusion, further optimization of ApoE-functionalized polyplexes and more sophisticated in vitro models are required to achieve more successful in vitro-in vivo translation in future approaches., (© 2023. The Author(s).)

Introduction: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias., Methods: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement., Results: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary., Conclusion: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Heart failure (HF) refers to a group of clinical syndromes in which various heart diseases lead to the inability of cardiac output to meet the metabolic needs of the body's tissues. Cardiac metabolism requires enormous amounts of energy; thus, impaired myocardial energy metabolism is considered a key factor in the occurrence and development of HF. Mitochondria serve as the primary energy source for cardiomyocytes, and their regular functionality underpins healthy cardiac function. The mitochondrial quality control system is a crucial mechanism for regulating the functionality of cardiomyocytes, and any abnormality in this system can potentially impact the morphology and structure of mitochondria, as well as the energy metabolism of cardiomyocytes. Phosphoglycerate mutase 5 (PGAM5), a multifunctional protein, plays a key role in the regulation of mitochondrial quality control through multiple pathways. Therefore, abnormal PGAM5 function is closely related to mitochondrial damage. This article reviews the mechanism of PGAM5's involvement in the regulation of the mitochondrial quality control system in the occurrence and development of HF, thereby providing a theoretical basis for future in-depth research., Competing Interests: Declarations of interest The authors declare that they have no conflict of interest or financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults., Methods: We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10., Results: This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95-0.99), female sex (0.53; 0.36-0.77), hypertension (0.68; 0.54-0.85), depressive symptoms (2.68; 2.07-3.46), high OSA risk (2.11; 1.69-2.63), and poor sleep quality (2.12; 1.60-2.82)., Conclusion: EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS., (© 2024. The Author(s).)

Posterior ocular disease, a disease that accounts for 55% of all ocular diseases, can contribute to permanent vision loss if left without treatment. Due to the special structure of the eye, various obstacles make it difficult for drugs to reach lesions in the posterior ocular segment. Therefore, the development of highly permeable targeted drugs and delivery systems is particularly important. Exosomes are a class of extracellular vesicles at 30-150 nm, which are secreted by various cells, tissues, and body fluids. They carry various signaling molecules, thus endowing them with certain physiological functions. In this review, we describe the ocular barriers and the biogenesis, isolation, and engineering of exosomes, as exosomes not only have pharmacological effects but also are good nanocarriers with targeted properties. Moreover, their biocompatibility and immunogenicity are better than synthetic nanocarriers. Most importantly, they may have the ability to pass through the blood-eye barrier. Thus, they may be developed as both targeted nano-drugs and nano-delivery vehicles for the treatment of posterior ocular diseases. We focus on the current status and potential application of exosomes as targeted nano-drugs and nano-delivery vehicles in posterior ocular diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes is known to negatively affect male reproduction. Recent clinical results have confirmed that mesenchymal stem cell (MSC)-based therapies are safe and effective for the treatment of diabetes. However, the effect and potential mechanism through which MSC transplantation improves diabetes-derived male reproductive dysfunction are still unknown. In the present study, we first established a male T1D mouse model through intraperitoneal injection of streptozotocin for five consecutive days. Subsequently, we evaluated the blood glucose levels, fertility, and histology and immunology of the pancreas, testes, and penis of T1D mice with or without transplantation of menstrual blood-derived endometrial stem cells (MenSCs) or umbilical cord mesenchymal stem cells (UCMSCs). Glucose was added to the medium in which the Leydig cells were cultured to imitate high glucose-injured cell viability. Subsequently, we evaluated the cellular viability, ROS levels, and mitochondrial membrane potential of Leydig cells treated with or without MenSC-conditioned medium (MenSC-CM) using a CCK8 assay, immunofluorescence, and flow cytometry. The targeted proteins are involved in the potential mechanism underlying MenSC-derived improvements, which was further validated via Western blotting. Collectively, our results indicated that MenSC transplantation significantly ameliorated reproductive dysfunction in male T1D mice by enhancing cellular antioxidative capacity and promoting angiogenesis. This study provides solid evidence and support for the application of MSCs to improve diabetes-induced male reproductive dysfunction., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Capacity-limited visual working memory (VWM) requires that individuals have sufficient memory space and the ability to filter distractors. Negative emotional states are known to impact VWM storage, yet their influence on distractor filtering within VWM remains underexplored. We conducted direct neural measurement of participants (n = 56) who conducted a lateralized change detection task with distractors, while manipulating the emotional state by presenting neutral or negative images before each trial. We found a detrimental effect of distractors on memory accuracy under both neutral and negative emotional states. Using the event-related potential (ERP) component, contralateral delay activity (CDA; sensitive to VWM load), to observe the VWM load in each condition, we found that in the neutral state, the participants showed significantly higher late CDA amplitudes when remembering 4 targets compared with 2 targets and 2 targets with 2 distractors but no significant difference when remembering 2 targets compared with 2 targets with 2 distractors. In the negative state, no significant CDA amplitude differences were evident when remembering 4 targets and 2 targets, but CDA was significantly higher when remembering 2 targets with 2 distractors compared with 2 targets. These results suggest that the maximum number of items participants could store in VWM was lower under negative emotional states than under neutral emotional states. Importantly, the participants could filter out distractors when in a neutral emotional state but not in a negative emotional state, indicating that negative emotional states impair their ability to filter out distractors in VWM., (© 2024. The Author(s).)

Achieving efficient and stable photocatalytic degradation of xylene hinges on the advancement of photocatalytic materials with outstanding visible light activity. This low-carbon strategy serves as a promising solution to combat air pollution effectively. In this study, we synthesized a Z-scheme heterojunction Ag@CuO/UiO-66-NH 2 nanocomposite by hydrothermal method to investigate its photodegradation properties for xylene gas under visible light conditions. XRD, XPS, SEM, FTIR, and UV-vis analyses were employed to confirm the presence of the Z-scheme heterojunction. The CuO/UiO-66-NH 2 (CuU-2) composite has high photocatalytic activity, which is 2.37 times that of the original UiO-66-NH 2 . The incorporation of Z-scheme heterojunction facilitates efficient charge transfer and separation, leading to a substantial enhancement in photocatalytic activity. The Ag@CuO/UiO-66-NH 2 (Ag-1@CuU) composite has the highest photocatalytic activity with a degradation efficiency of 84.12%, which is 3.36 times and 1.41 times that of UiO-66-NH 2 and CuO/UiO-66-NH 2 , respectively. The silver cocatalyst improves the absorption capacity of the composite material to visible light, makes the ultraviolet visible absorption edge redshift, and significantly improves the photocatalytic performance. This study introduces a novel approach for xylene gas degradation and offers a versatile strategy for designing and synthesizing metal-organic framework (MOF)-based photocatalysts with exceptional performance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Minimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies., Methods: A total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis., Results: A total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM., Conclusions: The presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables., (© 2023. Society of Surgical Oncology.)

Purpose: The medico-legal risk associated with application of medical directives in the emergency department (ED) is unknown. The objective of this study was to describe and analyze factors associated with medico-legal risk in cases involving medical directives in the ED., Methods: We conducted a descriptive analysis of closed medico-legal cases [hospital complaints, regulatory authority (i.e., College) complaints, and civil legal actions] involving emergency physicians in Canadian EDs involving medical directives (alternate terms including "standing order", "nursing initiated", "nurse initiated", "nursing order", "triage initiated", "triage ordered", "directive", "ED protocol", and "ED's protocol"). We used data from closed cases involving the Canadian Medical Protective Association from January 2016 until December 2021. We abstracted descriptive factors of the cases and used a framework for contributing factors classification., Results: From 2016 until 2021, 43,332 cases were closed and 1957 involved emergency physicians for which there was medico-legal information available for analysis. In all, 28 involved emergency physicians and medical directives. Situational awareness, team communication, and issues with clinical decision-making were the most important factors contributing to harm and medico-legal risk. Peer experts were critical of physicians not reviewing all results available for patients when initiated through a directive, misinterpreting test results, a less than thorough initial assessment, and of failing to reassess patients or re-order investigations when indicated., Conclusion: Our findings suggest that the medico-legal risk exposure from the use of medical directives in the ED is low. Emergency departments may consider implementing systems to support adherence to medical directive policies, ensure physicians are alerted when medical directives are completed in a timely fashion, and leverage tools to notify the healthcare team when results have not been reviewed., (© 2023. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)