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Puerarin, an isoflavone, exhibits protective effects against liver damage. This study investigated the effects of puerarin on the growth, liver immunity, and antioxidant capacity of yellowfin seabream fed with oxidized fish oil. A total of 135 yellowfin seabream (13.00±0.05 g) were randomly divided into nine tanks (15 fish per tank), and fed with three types of diets for 56 days: a normal control fed with 6 % fresh fish oil (NC), an experimental control fed with 6 % oxidized fish oil (OFO), and a treatment fed with 6 % oxidized fish oil and supplemented with 400 mg/kg puerarin (OFP). Results showed, oxidized fish oil decreased the growth of fish, caused liver damage, and suppressed the fish's immunity. Compared to the NC group, the weight gain (WG) and specific growth rate (SGR) of the fish in the OFO group were significantly reduced; the activities of superoxide dismutase (SOD) and catalase (CAT) in serum were significantly decreased; liver morphology showed loose cytoplasm with a large amount of fatty degeneration; the lysozyme (LZM) activity in serum and liver was significantly reduced. On the other hand, compared to the NC and OFO groups, the WG and SGR of fish in the OFP group were significantly improved. Additionally, compared to the OFO group, the serum SOD and liver CAT activities in the fish of the OFP group were significantly increased, and the MDA content in serum and liver was significantly reduced. The extensive fatty degeneration in the liver was alleviated. The LZM activity in the serum and liver of fish in the OFP group was significantly higher than that in the OFO group, returning to the levels of the NC group. Meanwhile, puerarin significantly enhanced the expression of Nrf2. In conclusion, puerarin alleviated the adverse reactions induced by oxidized fish oil and promoted the growth of yellowfin seabream.

This study was conducted to investigate the effects of puerarin on growth, digestive enzymes, antioxidant capacity, immunity and liver health of Acanthopagrus latus. Four diets were formulated: a control diet (C) and C supplemented with 200, 400, and 600 mg/kg puerarin (CP2, CP4, and CP6, respectively) and a eight-week feeding trial was conducted of fish. The results showed that the addition of 400 mg/kg puerarin significantly increased weight gain (WG), specific growth rate (SGR), and decreased the feed conversion ratio (FCR) compared to C group. Dietary supplementation with 600 mg/kg puerarin significantly increased lipase (LPS) activity compared to the C group. The addition of 200 mg/kg puerarin significantly reduced low-density lipoprotein cholesterol (LDL-C) and 400 mg/kg puerarin significantly reduced total cholesterol (T-CHO), triglycerides (TG) and HDL-C compared to the C group. Dietary supplementation with 400 mg/kg puerarin significantly increased serum and liver glutathione (GSH) activity and decreased malondialdehyde (MDA) content compared to the C group. Addition of 400 mg/kg puerarin significantly increased liver catalase (CAT) activity compared to the C group. Supplementation of 600 mg/kg and 400 mg/kg of puerarin significantly increased serum alkaline phosphatase (AKP) and lysozyme (LZM) activities, respectively. Compared to the C group, the addition of 200 mg/kg of puerarin significantly increased the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) in the liver. CP4-feeding significantly upregulated the expression of nrf2, ho-1, and gclc while downregulating the expression of keap1 compared to the C group. The addition of puerarin significantly reduced the expression of tnf-α and il-6 compared to the C group. Supplementation of 200 mg/kg puerarin significantly reduced the expression of bax compared to the C group. In conclusion, dietary supplementation with puerarin had positive effects on the growth, digestive enzymes, antioxidant capacity, immunity, and liver health of fish, particularly at 503.5 mg/kg.

In this paper, semideterministic multi-input multi-output (MIMO) channel modeling is proposed for a tunnel with two types of cross sections. To be more consistent with the MIMO propagation characteristics of the measured data, ray tracing (RT) is used to simulate the specular components (SCs) and a directed path channel modeling method based on directive scattering model (DSM) is used to simulate the diffuse components (DCs), which has an important contribution in MIMO channel capacity. The performance of the proposed model is compared in terms of delay domain, angle domain, and channel capacity. By analyzing the DSM and the propagation graph based on the Lambertian scattering model (LSM), it was demonstrated that the proposed method is more suitable in terms of comprehensive performance.

As a new display technology, electrowetting display (EWD) has many excellent display characteristics, such as paper-like, low power consumption, quick response and full color. These characteristics make EWD devices very suitable for portable devices. However, the gray-scale distortion caused by the contact angle hysteresis of EWDs seriously affects the accuracy of gray-scale display. To improve this phenomenon, the hysteresis curve of an EWD panel was studied according to the motion characteristics of advancing contact angle and receding contact angle of oil in a pixel. Then, a driving scheme for EWDs using alternating current (AC) voltage instead of direct current (DC) voltage was proposed in this paper. And the advantages and disadvantages of the driving scheme at different AC frequencies from 90 to 2,700 Hz were analyzed through experiments. According to the stability of aperture ratio in EWDs, a 470 Hz AC driving scheme was determined. Experimental results showed that the aperture ratio distortion of EWDs could be reduced from 35.82 to 5.97%, which significantly improved the display performance of pixel units.

Summary: Rechargeable aqueous Zn/manganese dioxide (Zn/MnO2) batteries are attractive energy storage technology owing to their merits of low cost, high safety, and environmental friendliness. However, the β-MnO2 cathode is still plagued by the sluggish ion insertion kinetics due to the relatively narrow tunneled pathway. Furthermore, the energy storage mechanism is under debate as well. Here, β-MnO2 cathode with enhanced ion insertion kinetics is introduced by the efficient oxygen defect engineering strategy. Density functional theory computations show that the β-MnO2 host structure is more likely for H+ insertion rather than Zn2+, and the introduction of oxygen defects will facilitate the insertion of H+ into β-MnO2. This theoretical conjecture is confirmed by the capacity of 302 mA h g−1 and capacity retention of 94% after 300 cycles in the assembled aqueous Zn/β-MnO2 cell. These results highlight the potentials of defect engineering as a strategy of improving the electrochemical performance of β-MnO2 in aqueous rechargeable batteries. : Energy Storage; Nanomaterials; Energy Materials Subject Areas: Energy Storage, Nanomaterials, Energy Materials

Abstract Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Tripartite motif containing 55 (TRIM55), also known as muscle-specific ring finger 2 (Murf2), belongs to the TRIM protein family and serves as an E3 ligase. Recently, the function and mechanism of TRIM55 in the advancement of solid tumors have been elucidated. However, the role of TRIM55 and its corresponding protein substrates in HCC remains incompletely explored. In this study, we observed a significant reduction in TRIM55 expression in HCC tissues. The downregulation of TRIM55 expression correlated with larger tumor size and elevated serum alpha-fetoprotein (AFP), and predicted unfavorable overall and tumor-free survival. Functional experiments demonstrated that TRIM55 suppressed the proliferation, migration, and invasion of HCC cells in vitro, as well as hindered HCC growth and metastasis in vivo. Additionally, TRIM55 exhibited a suppressive effect on HCC angiogenesis. Mechanistically, TRIM55 interacted with nuclear factor 90 (NF90), a double-stranded RNA-binding protein responsible for regulating mRNA stability and gene transcription, thereby facilitating its degradation via the ubiquitin-proteasome pathway. Furthermore, TRIM55 attenuated the association between NF90 and the mRNA of HIF1α and TGF-β2, consequently reducing their stability and inactivating the HIF1α/VEGF and TGFβ/Smad signaling pathways. In conclusion, our findings unveil the important roles of TRIM55 in suppressing the progression of HCC partly by promoting the degradation of NF90 and subsequently modulating its downstream pathways, including HIF1α/VEGF and TGFβ/Smad signaling.

Abstract UBE2C, a ubiquitin-conjugating enzyme, functions as an oncogene in different types of human cancers. Nonetheless, the exact influence of UBE2C on the development of HCC via regulation of ubiquitination remains uncertain. Here, we found that UBE2C displayed elevated levels of expression in HCC and was associated with an unfavorable prognosis, as evidenced by the analysis of the TCGA database and the examination of clinical specimens. The role of UBE2C in HCC revealed its ability to promote the growth and metastasis of HCC. Mechanistically, UBE2C activated Notch signaling, as evidenced by the upregulation of N1ICD and Hes1, crucial components of the Notch pathway, and activation of the RBP-JK luciferase reporter by UBE2C. Finally, rescue experiments demonstrated that the oncogenic role of UBE2C was eliminated through treatment with the Notch inhibitor DAPT, while overexpression of N1ICD alleviated the anticarcinogenic impact of knockdown of UBE2C. Altogether, the results of our study indicate that UBE2C plays a role in the activation of Notch signaling and could potentially serve as a viable target for therapeutic interventions in HCC.

Abstract Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy.

Cerebral edema caused by blood–brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell–derived neural stem cell exosomes (hiPSC–NSC–Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC–NSC–Exos on blood–brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC–NSC–Exos mitigated neurological deficits, enhanced blood–brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC–NSC–Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post–intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC–NSC–Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood–brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood–brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

The incidence of colorectal cancer is relatively high in our country, with the majority of patients being diagnosed at an advanced stage. For individuals with advanced-stage colorectal cancer, conversion or neoadjuvant therapy is frequently necessitated to facilitate surgical intervention and achieve a curative effect. And about 10% to 30% of colon cancer patients are complicated with intestinal obstruction. Surgical intervention remains the primary treatment for managing intestinal obstructions, albeit with a considerable risk of perioperative mortality and an increased likelihood of postoperative complications. PDT, as a neoadjuvant treatment for colon cancer, can shrink the local tumor and relieve obstruction, and is effective in colon cancer combined with obstruction. Robotic surgery has the advantages of high stability and low trauma, and compared with laparoscopic colon cancer surgery, robotic surgery can achieve better results. Fluorescent laparoscopic clarifies the location and size of the tumor lesion, allowing for greater precision when removing colon cancer lesions in robotic surgery. Therefore, in the treatment of colon cancer, PDT can offer an opportunity for surgery after relieving obstruction in patients with obstructive colon cancer. Additionally, when combined with fluorescent laparoscopic robotic colon cancer surgery, it provides a novel treatment approach for patients with obstructive colon cancer. Preoperative photodynamic neoadjuvant therapy combined with robotic colon cancer surgery has not yet been reported. Here, we report a case of colon cancer with obstruction, preoperative TNM stage was T4N1, and the lesion had caused intestinal stenosis. After four sessions of PDT, the patient’s intestinal lumen was unobstructed and the lesion had regressed. After evaluation, fluorescent laparoscopic localization and visualization of lymph nodes combined with robotic colon cancer resection were performed. Postoperative pathology showed that the patient’s tumor regression grade was grade 1. The patient’s tumor was completely resected with good resection effect. No tumor invasion was found on both sides of the resection margin, and the patient did not relapse after surgery.

Genetic sequencing has revolutionized immunotherapy in colorectal cancer (CRC). Recent clinical trials have revealed a positive response to immunotherapy-based systemic therapies in CRC patient subgroups with microsatellite instability (MSI)-High or DNA polymerase epsilon (POLE) mutation. However, the unsatisfactory response rates was the major limitation in real-world practice of the precision immunotherapy in CRC. Adding photodynamic therapy (PDT) to systemic immunotherapy has showed synergetic anti-tumor effect by modulating tumor microenvironment, while the eligible patient’s subgroups which would benefit from this combination remained equivocal. Here we reported a synchronous colorectal cancer patient with MSI-High and POLE mutation who had accelerated response in less than 2 cycles (42 days) of immunotherapy-based systemic therapies after tumor-directed PDT and has remained progression-free by far. This case enlightened the synergetic effect of PDT in immunotherapy-treated CRC patients, with the MSI and POLE-mutation status as predictors of survival benefits.

[INLINE:1] We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury. However, its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear. In this study, we first used an HT22 scratch injury model to mimic traumatic brain injury, then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p. We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress. Furthermore, luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α, while an IRE1α functional salvage experiment confirmed that miR-124-3p targeted IRE1α and reduced its expression, thereby inhibiting endoplasmic reticulum stress in injured neurons. Finally, we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced. These findings suggest that, after repetitive mild traumatic brain injury, miR-124-3 can be transferred from microglia-derived exosomes to injured neurons, where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress. Therefore, microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

Abstract HSPA13, an important member of the heat shock protein family, plays an essential role in the oncogenesis of many organs, but the mechanism and function in hepatocellular carcinoma (HCC) is still unclear. In the present study, we found that HSPA13 was highly expressed in HCC and predicted poor clinical prognosis. Upregulation of HSPA13 was significantly associated with vascular invasion in HCC patients. Functionally, knockdown experiments demonstrated that HSPA13 promoted HCC proliferation, migration, and invasion. Mechanistic investigation showed that HSPA13 could interact with TANK to inhibit its ubiquitination and degradation. In addition, the expression of HSPA13 and TANK were positively correlated in HCC tissues. To conclude, the present study uncovers the oncogenic function of HSPA13 in the progression of HCC by regulating the stability of TANK. These findings suggest that HSPA13 and TANK may serve as promising targets for the diagnosis and treatment of HCC.

Piezoelectric inkjet printing technology, known for its high precision and cost-effectiveness, has found extensive applications in various fields. However, the issue of residual vibration significantly limits its printing quality and efficiency. This paper presents a method for suppressing residual vibration based on the particle swarm optimization (PSO) algorithm. Initially, an improved PI model considering the nonlinear hysteresis characteristics of piezoelectric ceramics is established, and the model is identified through a strain gauge circuit to ensure its accuracy in describing the nonlinear hysteresis characteristics. Subsequently, a dynamic model of the piezoelectric inkjet printing system is constructed, with precise parameter identification achieved using the self-induction principle. This enables precise simulation of residual vibration. Finally, the driving waveform is optimized based on the PSO algorithm, with iterative calculations employed to find the optimal combination of driving waveform parameters, effectively suppressing residual vibration while ensuring sufficient injection energy. The results indicate that this method significantly reduces the amplitude of residual vibration, thereby effectively enhancing printing quality and stability. This research offers a novel solution for residual vibration suppression in piezoelectric inkjet printing technology, potentially advancing its applications in printing and biofabrication.

Background: OA imposes a heavy burden on patients and society in that its mechanism is still unclear, and there is a lack of effective targeted therapy other than surgery. Methods: The osteoarthritis dataset GSE55235 was downloaded from the GEO database and analyzed for differential genes by limma package, followed by analysis of immune-related modules by xcell immune infiltration combined with the WGCNA method, and macrophage polarization-related genes were downloaded according to the Genecard database, and VennDiagram was used to determine their intersection. These genes were also subjected to gene ontology (GO), disease ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Using machine learning, the key osteoarthritis genes were finally screened. Using single gene GSEA and GSVA, we examined the significance of these key gene functions in immune cell and macrophage pathways. Next, we confirmed the correctness of the hub gene expression profile using the GSE55457 dataset and the ROC curve. Finally, we projected TF, miRNA, and possible therapeutic drugs using the miRNet, TargetScanHuman, ENCOR, and NetworkAnalyst databases, as well as Enrichr. Results: VennDiagram obtained 71 crossover genes for DEGs, WGCNA-immune modules, and Genecards; functional enrichment demonstrated NF-κB, IL-17 signaling pathway play an important role in osteoarthritis-macrophage polarization genes; machine learning finally identified CSF1R, CX3CR1, CEBPB, and TLR7 as hub genes; GSVA analysis showed that CSF1R, CEBPB play essential roles in immune infiltration and macrophage pathway; validation dataset GSE55457 analyzed hub genes were statistically different between osteoarthritis and healthy controls, and the AUC values of ROC for CSF1R, CX3CR1, CEBPB and TLR7 were more outstanding than 0.65. Conclusions: CSF1R, CEBPB, CX3CR1, and TLR7 are potential diagnostic biomarkers for osteoarthritis, and CSF1R and CEBPB play an important role in regulating macrophage polarization in osteoarthritis progression and are expected to be new drug targets.

Abstract Objectives To explore the diagnostic accuracy of ultrasound measurement of optic nerve sheath diameter (ONSD) and optic disc height (ODH) in detecting intracranial hypertension in non‐small‐cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM). Methods Seventy‐two patients with NSCLC‐LM and 65 patients with NSCLC were enrolled. The ONSD, ODH, eyeball transverse diameter (ETD), and eyeball vertical diameter (EVD) were measured by ultrasound. Subsequently, lumbar puncture was performed in NSCLC‐LM patients to measure cerebrospinal fluid pressure (CSFP), and intrathecal chemotherapy was regularly implemented. Pearson's correlation analysis was used to analyze the relationship between CSFP and ultrasound findings. The diagnostic accuracy of ONSD, ODH, and combined ONSD and ODH was evaluated by receiver operating characteristic (ROC) curve analysis and the corresponding area under the ROC curve (AUC). Results The ONSD, ODH, ONSD/ETD, and ONSD/EVD values were higher in the NSCLC‐LM group (all p 280 mmH2O were 0.787 (95% CI: 0.64–0.93, sensitivity 68.75%, specificity 91.07%), 0.885 (95% CI: 0.81–0.96, sensitivity 100%, specificity 69.64%), 0.765 (95% CI: 0.64–0.89, sensitivity 81.25%, specificity 64.29%), and 0.788 (95% CI: 0.64–0.93, sensitivity 56.25%, specificity 91.07%), respectively. When ONSD was combined with ODH, the AUC was 0.913 (95% CI: 0.83–0.99, sensitivity 87.85%, specificity 85.70%). Furthermore, intrathecal chemotherapy was associated with a downtrend in CSFP and ultrasound findings. Conclusion There are important advantages of using bedside ultrasonography for detecting elevated CSFP in NSCLC‐LM patients. Further research should be performed to evaluate the clinical significance of an enlarged ONSD and increased ODH in NSCLC‐LM.

Small extracellular vesicles(sEVs), a subset of extracellular vesicles with a bilateral membrane structure, contain biological cargoes, such as lipids, nucleic acids, and proteins. sEVs are crucial mediators of intercellular communications in the physiological and pathological processes of the central nervous system. Because of the special structure and complex pathogenesis of the brain, central nervous system disorders are characterized by high mortality and morbidity. Increasing evidence has focused on the potential of sEVs in clinical application for central nervous system disorders. sEVs are emerging as a promising diagnostic and therapeutic tool with high sensitivity, low immunogenicity, superior safety profile, and high transfer efficiency. This review highlighted the development of sEVs in central nervous system disorder clinical application. We also outlined the role of sEVs in central nervous system disorders and discussed the limitations of sEVs in clinical translation.

Confronting the challenge of identifying unknown fault types in rolling bearing fault diagnosis, this study introduces a multi-scale bearing fault diagnosis method based on transfer learning. Initially, a multi-scale feature extraction network, MBDCNet, is constructed. This network, by integrating the features of vibration signals at multiple scales, is dedicated to capturing key information within bearing vibration signals. Innovatively, this study replaces traditional convolution with dynamic convolution in MBDCNet, aiming to enhance the model’s flexibility and adaptability. Furthermore, the study implements pre-training and transfer learning strategies to maximally extract latent knowledge from source domain data. By optimizing the loss function and fine-tuning the learning rate, the robustness and generalization ability of the model in the target domain are significantly improved. The proposed method is validated on bearing datasets provided by Case Western Reserve University and Jiangnan University. The experimental results demonstrate high accuracy in most diagnostic tasks, achieving optimal average accuracy on both datasets, thus verifying the stability and robustness of our approach in various diagnostic tasks. This offers a reliable research direction in terms of enhancing the reliability of industrial equipment, especially in the field of bearing fault diagnosis.

Abstract The incidence of repetitive mild traumatic brain injury (rmTBI), one of the main risk factors for predicting neurodegenerative disorders, is increasing; however, its underlying mechanism remains unclear. As suggested by several studies, ferroptosis is possibly related to TBI pathophysiology, but its effect on rmTBI is rarely studied. Mesenchymal stromal cells (MSCs), the most studied experimental cells in stem cell therapy, exert many beneficial effects on diseases of the central nervous system, yet evidence regarding the role of MSCs in ferroptosis and post-rmTBI neurodegeneration is unavailable. Our study showed that rmTBI resulted in time-dependent alterations in ferroptosis-related biomarker levels, such as abnormal iron metabolism, glutathione peroxidase (GPx) inactivation, decrease in GPx4 levels, and increase in lipid peroxidation. Furthermore, MSC treatment markedly decreased the aforementioned rmTBI-mediated alterations, neuronal damage, pathological protein deposition, and improved cognitive function compared with vehicle control. Similarly, liproxstatin-1, a ferroptosis inhibitor, showed similar effects. Collectively, based on the above observations, MSCs ameliorate cognitive impairment following rmTBI, partially via suppressing ferroptosis, which could be a therapeutic target for rmTBI.

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Abstract The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill‐defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long‐term TAE is challenging due to blockade of the tumor‐supplying artery. Here, a super‐stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long‐term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long‐term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal‐to‐normal tissues ratio—even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long‐term embolization therapy in clinical practice and has great potential for a translational pipeline.

Background: Lung cancer is a major public health issue and an enormous burden on society in China. Most lung cancers occur in elderly patients with non-small cell lung cancer (NSCLC), and many factors limit their treatment options. Chemotherapy-free therapy can avoid psychological fear, treatment pain, and adverse reactions caused by chemotherapy. Patients with non-small cell lung cancer with tumour protein p53 (TP53) gene mutations or Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations tend to be more sensitive to anlotinib or programmed cell death protein 1 (PD-1) drugs. However, Kirsten rat sarcoma viral oncogene homologue is a proto-oncogene downstream of the epidermal growth factor receptor (EGFR) gene; therefore, if the Kirsten rat sarcoma viral oncogene homologue gene has an activating mutation, EGFR-targeted drug resistance may occur. Further studies are needed to explore whether patients with dual Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations can be treated with targeted immunotherapy without chemotherapy.Case presentation: A 74-year-old man was referred to the Lanzhou University Second Hospital due to chest tightness, shortness of breath, and weight loss for 2 months and was diagnosed with moderately to poorly differentiated adenocarcinoma. Laboratory examinations showed increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and CA199 levels, and gene sequencing indicated mutations in Kirsten rat sarcoma viral oncogene homologue and tumour protein p53. Immunohistochemical analysis showed positive PD-L1 and PD-1 expression. Peripheral blood immune checkpoint test using flow cytometry indicated that the PD-1 + CD8 levels were positive. After multi-disciplinary treatment, therapy with a combination of anlotinib and camrelizumab was initiated. Camrelizumab 200 mg was administered intravenously once every 3 weeks. Anlotinib 12 mg was administered orally daily before breakfast for 2 weeks with a week of rest in every cycle of 21 days. A reduction in alpha-fetoprotein, carcinoembryonic antigen, CA125, CA199, and CA724 levels was observed up to the first cycle, which decreased within the normal limits up to the second cycle and continued until the eighteenth cycle. The patient’s chest tightness, shortness of breath, weight loss, and other symptoms significantly improved following treatment. Computed tomography imaging showed that the neoplastic lesion was dramatically reduced. The patient is currently being followed-up for more than 2 years to evaluate the duration of the response.Conclusion: Chemotherapy-free immunotherapy combined with targeted therapy is an effective treatment for advanced non-small cell lung cancer in elderly patients with Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations. Such therapies should be supported with further clinical studies with larger sample sizes.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, which is susceptible in elderly people with declined mobility, athletes of full contact sports, military personnel and victims of domestic violence. It has been pathologically diagnosed in brain donors with a history of repetitive mild traumatic brain injury (rmTBI), but cannot be clinically diagnosed for a long time. By the continuous efforts by neuropathologists, neurologists and neuroscientists in recent 10 years, an expert consensus for the diagnostic framework of CTE was proposed in 2021 funded by the National Institute of Neurological Disorders and Stroke. The new consensus contributes to facilitating research in the field. However, it still needs to incorporate in vivo biomarkers to further refine and validate the clinical diagnostic criteria. From this, a single-center, observational cohort study has been being conducted by Tianjin Medical University General Hospital since 2021. As a pilot study of this clinical trial, the present research recruited 12 pairs of gender- and age-matched rmTBI patients with healthy subjects. Their blood samples were collected for exosome isolation, and multi-omics screening to explore potential diagnostic biomarkers in blood and its exosomes. The expression level of CHL1 protein, KIF2A mRNA, LIN7C mRNA, miR-297, and miR-1183 in serum and exosomes were found to be differentially expressed between groups. Besides, serum and exosomal CHL1, KIF2A, and miR-1183, as well as exosomal miR-297 were further verified as potential biomarkers for CTE by low-throughput assays. They are expected to contribute to establishing a novel set of CTE diagnostic signatures with classic neurodegenerative indicators in our future study, thereby updating the consensus diagnostic criteria for CTE by incorporating new evidence of the in vivo biomarkers.

Edge detection is a crucial step in many computer vision tasks, and in recent years, models based on deep convolutional neural networks (CNNs) have achieved human-level performance in edge detection. However, we have observed that CNN-based methods rely on pre-trained backbone networks and generate edge images with unwanted background details. We propose four new fusion difference convolution (FDC) structures that integrate traditional gradient operators into modern CNNs. At the same time, we have also added a channel spatial attention module (CSAM) and an up-sampling module (US). These structures allow the model to better recognize the semantic and edge information in the images. Our model is trained from scratch on the BIPED dataset without any pre-trained weights and achieves promising results. Moreover, it generalizes well to other datasets without fine-tuning.

Rolling bearing fault diagnosis is of great significance to the safe and reliable operation of manufacturing equipment. In the actual complex environment, the collected bearing signals usually contain a large amount of noises from the resonances of the environment and other components, resulting in the nonlinear characteristics of the collected data. Existing deep-learning-based solutions for bearing fault diagnosis perform poorly in classification performance under noises. To address the above problems, this paper proposes an improved dilated-convolutional-neural network-based bearing fault diagnosis method in noisy environments named MAB-DrNet. First, a basic model called the dilated residual network (DrNet) was designed based on the residual block to enlarge the model’s perceptual field to better capture the features from bearing fault signals. Then, a max-average block (MAB) module was designed to improve the feature extraction capability of the model. In addition, the global residual block (GRB) module was introduced into MAB-DrNet to further improve the performance of the proposed model, enabling the model to better handle the global information of the input data and improve the classification accuracy of the model in noisy environments. Finally, the proposed method was tested on the CWRU dataset, and the results showed that the proposed method had good noise immunity; the accuracy was 95.57% when adding Gaussian white noises with a signal-to-noise ratio of −6 dB. The proposed method was also compared with existing advanced methods to further prove its high accuracy.

Background and objective Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM. Methods Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient. Results Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P

Although there are still no satisfactory answers to the question of why we need to sleep, a better understanding of its function will help to improve societal attitudes toward sleep. Sleep disorders are very common in neurodegenerative diseases and are a key factor in the quality of life of patients and their families. Alzheimer’s disease (AD) is an insidious and irreversible neurodegenerative disease. Along with progressive cognitive impairment, sleep disorders and disturbances in circadian rhythms play a key role in the progression of AD. Sleep and circadian rhythm disturbances are more common in patients with AD than in the general population and can appear early in the course of the disease. Therefore, this review discusses the bidirectional relationships among circadian rhythm disturbances, sleep disorders, and AD. In addition, pharmacological and non-pharmacological treatment options for patients with AD and sleep disorders are outlined.

In the field of rough set, feature reduction is a hot topic. Up to now, to better guide the explorations of this topic, various devices regarding feature reduction have been developed. Nevertheless, some challenges regarding these devices should not be ignored: (1) the viewpoint provided by a fixed measure is underabundant; (2) the final reduct based on single constraint is sometimes powerless to data perturbation; (3) the efficiency in deriving the final reduct is inferior. In this study, to improve the effectiveness and efficiency of feature reduction algorithms, a novel framework named parallel selector for feature reduction is reported. Firstly, the granularity of raw features is quantitatively characterized. Secondly, based on these granularity values, the raw features are sorted. Thirdly, the reordered features are evaluated again. Finally, following these two evaluations, the reordered features are divided into groups, and the features satisfying given constraints are parallel selected. Our framework can not only guide a relatively stable feature sequencing if data perturbation occurs but can also reduce time consumption for feature reduction. The experimental results over 25 UCI data sets with four different ratios of noisy labels demonstrated the superiority of our framework through a comparison with eight state-of-the-art algorithms.

Neural inflammatory response is a crucial pathological change in intracerebral hemorrhage (ICH) which accelerates the formation of perihematomal edema and aggravates neural cell death. Although surgical and drug treatments for ICH have advanced rapidly in recent years, therapeutic strategies that target and control neuroinflammation are still limited. Exosomes are important carriers for information transfer among cells. They have also been regarded as a promising therapeutic tool in translational medicine, with low immunogenicity, high penetration through the blood-brain barrier, and ease of modification. In our previous research, we have found that exogenous administration of miRNA-124-overexpressed microglial exosomes (Exo-124) are effective in improving post-injury cognitive impairment. From this, we evaluated the potential therapeutic effects of miRNA-124-enriched microglial exosomes on the ICH mice in the present study. We found that the gene-edited exosomes could attenuate neuro-deficits and brain edema, improve blood–brain barrier integrity, and reduce neural cell death. Moreover, the protective effect of Exo-124 was abolished in mice depleted of Gr-1+ myeloid cells. It suggested that the exosomes exerted their functions by limiting the infiltration of leukocyte into the brain, thus controlling neuroinflammation following the onset of ICH. In conclusion, our findings provided a promising therapeutic strategy for improving neuroinflammation in ICH. It also opens a new avenue for intranasal delivery of exosome therapy using miRNA-edited microglial exosomes.

With the continuous development of intelligent manufacturing technology, the intelligent production line for the Industrial Internet of Things occupies an important position in the field of industrial intelligence. OPC UA is a standard for communication data exchange between intelligent production line devices. OPC UA can establish a unified information model for production line devices and improve the connectivity of heterogeneous networks. However, in industrial wireless network application scenarios, there are various types of sensing information and large amounts of data to be transmitted. Each type of data has different requirements for real-time. The traditional OPC UA communication method is difficult to achieve real-time and reliable transmission in intelligent production lines and can’t meet the transmission requirements of time-sensitive data. In this paper, we propose a real-time communication model of the OPC UA wireless network for intelligent production lines (UAMPDS). IEEE 802.15.4e TSCH is used as the wireless communication infrastructure, and OPC UA protocols are fused to this model. Meanwhile, we design a load-aware time-slot scheduling algorithm to dynamically allocate and schedule time slots according to the network topology and traffic load of each node. We also implement a dynamic preemptive resource scheduling strategy based on service differentiation to ensure real-time transmission of time-sensitive data. The experimental results show that this model achieves differentiated services based on data with different latency tolerance and effectively reduces the transmission latency of real-time service data under the constrained network resources. It can avoid the starvation phenomenon of low priority queues, and improves the overall quality of service of intelligent production line communication networks.

Sleep deprivation (SD) induces systemic inflammation that promotes neuronal pyroptosis. The purpose of this study was to investigate the effect of an antioxidant modafinil on neuronal pyroptosis and cognitive decline following SD. Using a mouse model of SD, we found that modafinil improved learning and memory, reduced proinflammatory factor (IL-1β, TNF-α, and IL-6) production, and increased the expression of anti-inflammatory factors (IL-10). Modafinil treatment attenuated inflammasome activity and reduced neuronal pyroptosis involving the NLRP3/NLRP1/NLRC4-caspase-1-IL-1β pathway. In addition, modafinil induced an upregulation of brain-derived neurotrophic factor (BDNF) and synaptic activity. These results suggest that modafinil reduces neuronal pyroptosis and cognitive decline following SD. These effects should be further investigated in future studies to benefit patients with sleep disorders.

Abstract Alzheimer’s disease (AD) has been a devastating public health with the development of global aging. Approaches for reducing the current AD epidemic are becoming a primary focus of human healthcare due to the lack of achieved lasting and complete remission strategies to treat AD with the characteristics of heterogeneity and complexity. Exosomes, which is the new emerging approach to intercellular communication, provide novel perspective on identified therapeutic strategies of AD. Mesenchymal stem cell-derived exosomes (MSC-exos) are emerging to be an appealing therapeutic tool for AD, with the donor-derived properties and the characteristics of minimal immunogenicity, effortless storage, nature delivery vehicles, and low risks of tumor formation based on the previous researches. In this review, we elaborate the mechanism of MSC-exos in the treatment of AD and discuss limitations in the clinical application.

Background and objective Leptomeningeal metastasis (LM) are a severe complication of non-small cell lung cancer (NSCLC), and normally accompanied by poor prognosis. For the patients with targetable mutations, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment, but the acquired TKI resistance is inextricable. The aim of this study is to analyze the different gene mutation spectrum and mutation frequency of the cerebrospinal fluid (CSF) and plasma in NSCLC patients with LM, and screen out the drug-resistant mutations so as to guide the choice of treatment accurately. Methods The paired CSF and plasma samples were collected from the NSCLC-LM patients with acquired TKI resistance. Next generation sequencing (NGS) was used to detect the gene variations of circulating tumor DNA (ctDNA). Results A total of 18 NSCLC patients with LM were collected. Of the basic mutations, 11 cases (61.11%) were EGFR, 6 cases (33.33%) were anaplastic lymphoma kinase (ALK), and 1 case (5.56%) was ROS proto-oncogene 1, receptor tyrosine kinase (ROS1). Tumor protein p53 gene (TP53) and mesenchymal-epithelial transition factor (MET) were the two most frequently accompanying mutated genes in CSF ctDNA. The detected mutation rate of CSF samples was higher than that of plasma samples (100.00% vs 66.67%, P=0.006), and the maximum allelic fractions were all higher in CSF than in plasma (P

Background and Objective Leptomeningeal metastasis (LM) is one of the most common causes of death in patients with advanced non-small cell lung cancer (NSCLC), which is defined as malignant cells spreading to meninges and cerebrospinal fluid (CSF). Therefore, early diagnosis and timely treatment are essential. CSF cytology is the gold standard for LM diagnosis, however, it has a low sensitivity for diagnosis and can’t be used to evaluate the treatment effect. The aim of this study was to assess the clinical value of serum and CSF tumor markers (TM) in the diagnosis and treatment of NSCLC patients with LM. Methods Nineteen patients with NSCLC-LM and 27 patients with nonmalignant neurological diseases (NMNDs) were included. We tested the levels and positive rates of carbohydrate antigen (CEA), carbohydrate antigen-125 (CA125), cytokeratin 19 fragments (CYFRA21-1) and neurone specific enolase (NSE) in CSF and serum, compared the sensitivity and specificity in the diagnosis of LM between different groups, and analyzed the correlation of detection between serum and CSF. Finally, we measured serum and CSF TM dynamically in 2 patients with NSCLC developing LM in an attempt to correlate these with the treatment response of extracranial and intracranial, respectively. Results The levels and positive rates of TM in CSF and serum in LM group were higher than those in NMNDs (P0.05). In CSF, CYFRA21-1 has the highest sensitivity (88.2%) and CEA has the best specificity (92.3%) to distinguish patients between LM and NMNDs. For combined detection of CEA, CA125, CYFRA 21-1 and NSE in CSF, when at least CEA or NSE was positive in patients with LM, the sensitivity and negative predictive value were 100.0%, and the specificity was 74.1%. When both CYFRA21-1 and NSE were positive, the specificity and positive predictive value were 100.0%, and the sensitivity was 78.9%. Furthermore, subgroup analysis showed that the detection rates of TM in CSF cytology positive population was higher than that in typical abnormalities magnetic resonance imaging population, but there was no statistical difference (P>0.05). The detection of TM between serum and CSF in LM patients had no significant correlation. Moreover, biochemical properties of CSF from ventricle and lumbar puncture are similar, therefore evaluating the levels of TM in serum and CSF dynamically can be used to assess the extracranial and intracranial treatment effect, respectively. Conclusion Our study demonstrates that Serum and CSF TM can work as an auxiliary clinical diagnostic tool, which has a potential value in early diagnosis of NSCLC patients with LM. Serial measurement of TM may play an important role in the clinical management of NSCLC patients with LM, which is worthy of further promotion and clinical application.

This paper proposes a functional safety and information security protection mechanism based on blockchain technology. The design of the basic level and integration level blockchain structure of CPS distributed architecture and related functional safety and information security measures are introduced. An effective communication judgment mechanism based on functional safety error threshold is proposed, which is stored and judged by smart contract. And a refund transaction with a clock is proposed to ensure the effective execution of the functional safety error threshold mechanism. The article takes cyber physical machine tool system as an example to describe the SIL judgment method of CPS physical equipment and functional safety loop and combines SIL with fault diagnosis and risk protection. Finally, the rationality of our proposed mechanism is proved by information security, functional security, real-time and maintainability.

BackgroundRepetitive mild traumatic brain injury (rmTBI) is closely associated with chronic traumatic encephalopathy (CTE). Neuroinflammation and neuropathological protein accumulation are key links to CTE progression. Exosomes play important roles in neuroinflammation and neuropathological protein accumulation and spread. Here, we explored the role of brain-derived exosomes (BDEs) in mice with rmTBI and how the inhibition of BDE release contributes to neuroprotection.MethodsGW4869 was used to inhibit exosome release, and behavioural tests, PET/CT and western blotting were conducted to explore the impact of this inhibition from different perspectives. We further evaluated cytokine expression by Luminex and microglial activation by immunofluorescence in mice with rmTBI after exosome release inhibition.ResultsInhibition of BDE release reversed cognitive impairment in mice with rmTBI, enhanced glucose uptake and decreased neuropathological protein expression. Inhibition of BDE release also changed cytokine production trends and enhanced microglial proliferation.ConclusionIn this study, we found that BDEs are key factor in cognitive impairment in mice with rmTBI and that microglia are the main target of BDEs. Thus, inhibition of exosome release may be a new strategy for improving CTE prognoses.

Most of data set can be represented in an asymmetric matrix. How to mine the uncertain information from the matrix is the primary task of data processing. As a typical unsupervised learning method, three-way k-means clustering algorithm uses core region and fringe region to represent clusters, which can effectively deal with the problem of inaccurate decision-making caused by inaccurate information or insufficient data. However, same with k-means algorithm, three-way k-means also has the problems that the clustering results are dependent on the random selection of clustering centers and easy to fall into the problem of local optimization. In order to solve this problem, this paper presents an improved three-way k-means algorithm by integrating ant colony algorithm and three-way k-means. Through using the random probability selection strategy and the positive and negative feedback mechanism of pheromone in ant colony algorithm, the sensitivity of the three k-means clustering algorithms to the initial clustering center is optimized through continuous updating iterations, so as to avoid the clustering results easily falling into local optimization. Dynamically adjust the weights of the core domain and the boundary domain to avoid the influence of artificially set parameters on the clustering results. The experiments on UCI data sets show that the proposed algorithm can improve the performances of three-way k-means clustering results and is effective in revealing cluster structures.

Amyloid-β (Aβ) is the predominant pathologic protein in Alzheimer’s disease (AD). The production and deposition of Aβ are important factors affecting AD progression and prognosis. The deposition of neurotoxic Aβ contributes to damage of the blood–brain barrier. However, the BBB is also crucial in maintaining the normal metabolism of Aβ, and dysfunction of the BBB aggravates Aβ deposition. This review characterizes Aβ deposition and BBB damage in AD, summarizes their interactions, and details their respective mechanisms.

Impairment in spatial navigation (SN) and structural network topology is not limited to patients with Alzheimer’s disease (AD) dementia and can be detected earlier in patients with mild cognitive impairment (MCI). We recruited 32 MCI patients (65.91 ± 11.33 years old) and 28 normal cognition patients (NC; 69.68 ± 10.79 years old), all of whom underwent a computer-based battery of SN tests evaluating egocentric, allocentric, and mixed SN strategies and diffusion-weighted and T1-weighted Magnetic Resonance Imaging (MRI). To evaluate the topological features of the structural connectivity network, we calculated its measures such as the global efficiency, local efficiency, clustering coefficient, and shortest path length with GRETNA. We determined the correlation between SN accuracy and network topological properties. Compared to NC, MCI subjects demonstrated a lower egocentric navigation accuracy. Compared with NC, MCI subjects showed significantly decreased clustering coefficients in the left middle frontal gyrus, right rectus, right superior parietal gyrus, and right inferior parietal gyrus and decreased shortest path length in the left paracentral lobule. We observed significant positive correlations of the shortest path length in the left paracentral lobule with both the mixed allocentric–egocentric and the allocentric accuracy measured by the average total errors. A decreased clustering coefficient in the right inferior parietal gyrus was associated with a larger allocentric navigation error. White matter hyperintensities (WMH) did not affect the correlation between network properties and SN accuracy. This study demonstrated that structural connectivity network abnormalities, especially in the frontal and parietal gyri, are associated with a lower SN accuracy, independently of WMH, providing a new insight into the brain mechanisms associated with SN impairment in MCI.

The cross‐talk between hepatic stellate cells (HSCs) and hepatic carcinoma cells contributes to hepatocellular carcinoma (HCC) progression, but the underlying mechanism is largely unknown. We report here that activated HSCs induce upregulation of nicotinamide N‐methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in HCC tissues were positively correlated with vascular invasion, increased serum HBV‐DNA levels, and distant metastasis. In addition, functional assays showed that NNMT promoted HCC cell invasion and metastasis by altering the histone H3 methylation on 27 methylation pattern and transcriptionally activating cluster of differentiation 44 (CD44). NNMT‐mediated N6‐methyladenosine modification of CD44 mRNA resulted in the formation of a CD44v3 splice variant, while its product 1‐methyl‐nicotinamide stabilized CD44 protein by preventing ubiquitin‐mediated degradation. Finally, NNMT was also shown to be a target of statins that inhibited metastasis of hepatoma cells. Taken together, our study shows for the first time that the NNMT/CD44v3 axis regulates HCC metastasis and presents NNMT as a promising prognostic biomarker and therapeutic target for HCC.

Leptomeningeal metastasis (LM) is one of the most severe complications of non-small-cell lung cancer (NSCLC), and its incidence is increasing gradually with the progress of targeted therapies. There are currently no standard guidelines for the therapy of LM. Intrathecal chemotherapy is the mainstay of treatment for NSCLC patients with LM, but the optimal drug, administration route and mode, and dosage remain unclear. We report a case of LM from NSCLC, who received the intrathecal chemotherapy with pemetrexed by Ommaya reservoir after prior targeted therapies. This local treatment improved the quality of life, and obtained the clearing of CSF cytology and stable lesions of LM without any notable side effects. After confirmation of LM, the patient has survived 17 months until now. Here we report the first case to demonstrate the potential effectiveness of intrathecal pemetrexed by Ommaya reservoir for the treatment of LM of NSCLC, summarize the safety and effectiveness of intrathecal chemotherapy in combination with related literatures, and provide a new strategy for local treatment of LM in clinical.

Abstract Background CDK5, an atypical member of the CDK family, play a significant role in the tumorigenesis of multiple organ, but CDK5 and its substrates in genesis and development of HCC is still unclear. Methods Expression of CDK5 in HCC tumor and paired adjacent noncancerous tissues from 90 patients were measured by Western blotting, immunohistochemistry, and real-time PCR. The role of CDK5 in cell function and tumorigenesis was explored in HCC cell lines, ex vivo xenografts and diethylnitrosamine induced HCC model. Furthermore, comparative phosphoproteomic screening identified the oncoprotein TPX2 as a new substrate of CDK5. We also identified the effect of CDK5/P25 interaction blocker tamoxifen on HCC cell growth and migration. Results CDK5 was increased in HCC tisues and the level of CDK5 was correlated with the severity of HCC based on patient recurrence and 5-year fatality rate. Exogenously expressed CDK5 but not kinase-dead CDK5 promoted proliferation, migration, and invasion of HCC cells. Functional ablation of CDK5 significantly inhibited the exacerbation of HCC cells. Xenograft implantation of HCC cells overexpressing CDK5 promoted tumorigenesis, and genetic knockdown of CDK5 reduced HCC growth and metastasis in vivo. More importantly, heterozygous knockout CDK5 (Cdk5+/−) attenuated HCC tumorigenesis induced by diethylnitrosamine. CDK5-mediated phosphorylation of TPX2 at serine 486 promoted its protein stability. TPX2 silence could restore HCC cell migration capability with overexpression CDK5. Treatment with tamoxifen inhibited cell growth and migration of HCC, demonstrating the role of active CDK5 in HCC. Conclusions Our results suggest activation of CDK5 is associated with HCC tumorigenesis. CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular proliferation and tumorigenicity.

In this study, a hoop-strain sensor was developed by embedding a bare fiber Bragg grating (FBG) sensor inside 3D printed Polylactic Acid (PLA) filament. Fabrication process of the hoop-strain sensor indicates that the initial temperature of the melted PLA is around 50 °C which is obviously lower than the printing temperature of the printer nozzle (around 200°C). A typical residual wavelength was found after the fabrication process of the hoop-strain sensor. The shrinkage deformation of the present sensor was around 208 με after fabrication. The hoop-strain sensor was flexible and can be used to measure both circumferential strain change and contact pressure between hoop-strain sensors and cylinders. Calibration tests for elongation measurement indicate that the sensitivity and minimum resolution with respect to strain change are 4.04 nm/% and 3.574 με, respectively. The obtained measurement sensitivity and resolution for pressure measurement were 0.0035 nm/kPa, and 0.286 kPa, respectively. The maximum measurement ranges of the hoop-strain sensor for strain and pressure measurement are larger than 1% and 800 kPa, respectively.

Prolonged neuroinflammation is a driving force for neurodegenerative disease, and agents against inflammatory responses are regarded as potential treatment strategies. Here we aimed to evaluate the prevention effects on gliosis by dexamethasone (DEX), an anti-inflammation drug. We used DEX to treat the nicastrin conditional knockout (cKO) mouse, a neurodegenerative mouse model. DEX (10 mg/kg) was given to 2.5-month-old nicastrin cKO mice, which have not started to display neurodegeneration and gliosis, for 2 months. Immunohistochemistry (IHC) and Western blotting techniques were used to detect changes in neuroinflammatory responses. We found that activation of glial fibrillary acidic protein (GFAP) positive or ionized calcium binding adapter molecule1 (Iba1) positive cells was not inhibited in nicastrin cKO mice treated with DEX as compared to those treated with saline. These data suggest that DEX does not prevent or ameliorate gliosis in a neurodegenerative mouse model when given prior to neuronal or synaptic loss.

Over recent years, traditional manufacturing factories have been accelerating their transformation and upgrade toward smart factories, which are an important concept within Industry 4.0. As a key communication technology in the industrial internet architecture, time-sensitive networks (TSNs) can break through communication barriers between subsystems within smart factories and form a common network for various network flows. Traditional routing algorithms are not applicable for this novel type of network, as they cause unnecessary congestion and latency. Therefore, this study examined the classification of TSN flows in smart factories, converted the routing problem into two graphical problems, and proposed two heuristic optimization algorithms, namely GATTRP and AACO, to find the optimal solution. The experiments showed that the algorithms proposed in this paper could provide a more reasonable routing arrangement for various TSN flows with different time sensitivities. The algorithms could effectively reduce the overall delay by up to 74% and 41%, respectively, with promising operating performances.

With the widespread use of industrial Internet technology in intelligent production lines, the number of task requests generated by smart terminals is growing exponentially. Achieving rapid response to these massive tasks becomes crucial. In this paper we focus on the multi-objective task scheduling problem of intelligent production lines and propose a task scheduling strategy based on task priority. First, we set up a cloud-fog computing architecture for intelligent production lines and built the multi-objective function for task scheduling, which minimizes the service delay and energy consumption of the tasks. In addition, the improved hybrid monarch butterfly optimization and improved ant colony optimization algorithm (HMA) are used to search for the optimal task scheduling scheme. Finally, HMA is evaluated by rigorous simulation experiments, showing that HMA outperformed other algorithms in terms of task completion rate. When the number of nodes exceeds 10, the completion rate of all tasks is greater than 90%, which well meets the real-time requirements of the corresponding tasks in the intelligent production lines. In addition, the algorithm outperforms other algorithms in terms of maximum completion rate and power consumption.

In recent years, self-supervised monocular depth estimation has gained popularity among researchers because it uses only a single camera at a much lower cost than the direct use of laser sensors to acquire depth. Although monocular self-supervised methods can obtain dense depths, the estimation accuracy needs to be further improved for better applications in scenarios such as autonomous driving and robot perception. In this paper, we innovatively combine soft attention and hard attention with two new ideas to improve self-supervised monocular depth estimation: (1) a soft attention module and (2) a hard attention strategy. We integrate the soft attention module in the model architecture to enhance feature extraction in both spatial and channel dimensions, adding only a small number of parameters. Unlike traditional fusion approaches, we use the hard attention strategy to enhance the fusion of generated multi-scale depth predictions. Further experiments demonstrate that our method can achieve the best self-supervised performance both on the standard KITTI benchmark and the Make3D dataset.