Robust Micro-Sized and Defect-Rich Carbon-Carbon Composites as Advanced Anodes for Potassium-Ion Batteries.

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Engineering CSFe Bond Confinement Effect to Stabilize Metallic-Phase Sulfide for High Power Density Sodium-Ion Batteries.

Metallic-phase iron sulfide (e.g., Fe7 S8 ) is a promising candidate for high power density sodium storage anode due to the inherent metal electronic conductivity and unhindered sodium-ion diffusion kinetics. Nevertheless, long-cycle stability can not be achieved simultaneously while designing a fast-charging Fe7 S8 -based anode. Herein, Fe7 S8 encapsulated in carbon-sulfur bonds doped hollow carbon fibers (NHCFs-S-Fe7 S8 ) is designed and synthesized for sodium-ion storage. The NHCFs-S-Fe7 S8 including metallic-phase Fe7 S8 embrace higher electron specific conductivity, electrochemical reversibility, and fast sodium-ion diffusion. Moreover, the carbonaceous fibers with polar CSFe bonds of NHCFs-S-Fe7 S8 exhibit a fixed confinement effect for electrochemical conversion intermediates contributing to long cycle life. In conclusion, combined with theoretical study and experimental analysis, the multinomial optimized NHCFs-S-Fe7 S8 is demonstrated to integrate a suitable structure for higher capacity, fast charging, and longer cycle life. The full cell shows a power density of 1639.6 W kg-1 and an energy density of 204.5 Wh kg-1 , respectively, over 120 long cycles of stability at 1.1 A g-1 . The underlying mechanism of metal sulfide structure engineering is revealed by in-depth analysis, which provides constructive guidance for designing the next generation of durable high-power density sodium storage anodes.

Enhanced optical forces on coupled chiral particles at arbitrary order exceptional points.

Exceptional points (EPs)-non-Hermitian degeneracies at which eigenvalues and eigenvectors coalesce-can give rise to many intriguing phenomena in optical systems. Here, we report a study of the optical forces on chiral particles in a non-Hermitian system at EPs. The EPs are achieved by employing the unidirectional coupling of the chiral particles sitting on a dielectric waveguide under the excitation of a linearly polarized plane wave. Using full-wave numerical simulations, we demonstrate that the structure can give rise to enhanced optical forces at the EPs. Higher order EPs in general can induce stronger optical forces. In addition, the optical forces exhibit an intriguing "skin effect": the force approaches the maximum for the chiral particle at one end of the lattice. The results contribute to the understanding of optical forces in non-Hermitian systems and can find applications in designing novel optical tweezers for on-chip manipulations of chiral particles.

Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.

PVP with or without microwave ablation for the treatment of painful spinal metastases from NSCLC: a retrospective case-control study.

OBJECTIVE: To compare the clinical efficacy of percutaneous vertebroplasty (PVP) alone and microwave ablation (MWA) combined with PVP for the treatment of painful spinal metastases from non-small cell lung cancer (NSCLC). METHODS: From October 2014 to October 2021, the data of 58 NSCLC patients with refractory painful spinal metastases (visual analog scale score ≥ 5) were retrospectively collected and analyzed. Patients in Group A (n = 30) and Group B (n = 28) received PVP alone and MWA combined with PVP, respectively. The primary endpoint was pain relief. The secondary endpoints were quality of life (QoL), local tumor progression (LTP), and complications. RESULTS: The technical success rate was 100% in both groups. Patients in both groups showed similar pain relief at 1-12 weeks, but patients in Group B still showed sustained pain relief at 24 weeks compared to those in Group A (p = 0.03). The assessment of QoL showed similar changes. LTP (33.00% vs. 7.14%, p = 0.02) and cement leakage rates (40.00% vs. 7.14%, p = 0.03) were lower in Group B. The multivariate analysis demonstrated spinal metastases with a maximum diameter ≤ 3.0 cm (p = 0.027) and MWA combined with PVP (p = 0.028) were two independent protective factors for LTP. For cement leakage, spinal metastases with vertebral body compression (p = 0.019) was an independent risk factor, while MWA combined with PVP (p = 0.042) was an independent protective factor. CONCLUSION: MWA combined with PVP for painful spinal metastases from NSCLC performed more sustained pain relief (>6 months) and ultimately improved QoL with lower LTP and cement leakage rates, compared to PVP alone.

Novel 1,3,4-Thiadiazole Derivatives: Synthesis, Antiviral Bioassay and Regulation the Photosynthetic Pathway of Tobacco against TMV Infection.

Tobacco mosaic virus (TMV) is a systemic virus that poses a serious threat to crops worldwide. In the present study, a series of novel 1-phenyl-4-(1,3,4-thiadiazole-5-thioether)-1H-pyrazole-5-amine derivatives was designed and synthesized. In vivo antiviral bioassay results indicated that some of these compounds exhibited excellent protective activity against TMV. Among the compounds, E2 (EC50 = 203.5 µg/mL) was superior to the commercial agent ningnanmycin (EC50 = 261.4 µg/mL). Observation of tobacco leaves infected with TMV-GFP revealed that E2 could effectively inhibit the spread of TMV in the host. Further plant tissue morphological observation indicated that E2 could induce the tight arrangement and alignment of the spongy mesophyll and palisade cells while causing stomatal closure to form a defensive barrier to prevent viral infection in the leaves. In addition, the chlorophyll content of tobacco leaves was significantly increased after treatment with E2, and the net photosynthesis (Pn) value was also increased, which demonstrated that the active compound could improve the photosynthetic efficiency of TMV-infected tobacco leaves by maintaining stable chlorophyll content in the leaves, thereby protecting host plants from viral infection. The results of MDA and H2O2 content determination revealed that E2 could effectively reduce the content of peroxides in the infected plants, reducing the damage to the plants caused by oxidation. This work provides an important support for the research and development of antiviral agents in crop protection.

Optical force and torque on small particles induced by polarization singularities.

Optical forces in the near fields have important applications in on-chip optical manipulations of small particles and molecules. Here, we report a study of optical force and torque on small particles induced by the optical polarization singularities of a gold cylinder. We show that the scattering of the cylinder generates both electric and magnetic C lines (i.e., lines of polarization singularities) in the near fields. The intrinsic spin density of the C lines can induce complex optical torque on a dielectric/magnetic particle, and the near-field evolutions of the C lines are accompanied by a gradient force on the particle. The force and torque manifest dramatic spatial variations, providing rich degrees of freedom for near-field optical manipulations. The study, for the first time to our knowledge, uncovers the effect of optical polarization singularities on light-induced force and torque on small particles. The results contribute to the understanding of chiral light-matter interactions and can find applications in on-chip optical manipulations and optical sensing.

Light funneling by spin-orbit-coupled chiral particles on an arbitrary order exceptional surface.

Optical systems at non-Hermitian exceptional points (EPs) have intriguing properties that promise novel applications in light manipulations. Here, we realize an arbitrary order exceptional surface (ES), i.e., a surface of arbitrary order EPs, in chiral particles that couple with each other via the photonic spin-orbit interaction mediated by a dielectric waveguide. The chirality of the particles enables selective excitation of the chiral dipole modes by linearly polarized light. The unidirectional coupling of the chiral dipole modes gives rise to the ES in the parameter space defined by the material loss and coupling distance of the particles. We apply the system to realize a light funnel that can convert free-space plane waves to guided waves and funnel the incident light energy into a ring resonator. The results can find applications in designing optical switches, on-chip conversion of guided waves, and harvest of light energy.

Design, Synthesis and in Vitro Antifungal Mechanism of Novel Phenylalanine Derivatives.

To explore novel molecules with unique mechanisms against plant pathogenic fungi, a series of phenylalanine derivatives containing a 1,3,4-oxadiazothioether moiety were designed and synthesized. Bioassays revealed that some target compounds at 100 µg/mL exhibited excellent antifungal activities against Thanatephorus cucumeris, such as G6 (92.1 %), G10 (94.3 %), G18 (99.1 %), and G19 (98.7 %), better than that of the commercial fungicide azoxystrobin (90.6 %), and the EC50 value of G10 against T. cucumeris was 31.9 µg/mL. Further mechanism studies of T. cucumeris treated with G10 demonstrated that this compound can affect the growth of mycelia by disrupting the integrity of the membrane, and the higher the concentration of the compound is, the greater the degree of membrane integrity damage, similar to the commercial fungicide azoxystrobin. These conclusions provide important information for further mechanism studies of this series of phenylalanine derivatives.

Is coronavirus-related research becoming more interdisciplinary? A perspective of co-occurrence analysis and diversity measure of scientific articles.

The outbreak of coronavirus disease 2019 (COVID-19) has had a significant repercussion on the health, economy, politics and environment, making coronavirus-related issues more complicated and difficult to adequately address by relying on a single field. Interdisciplinary research can provide an effective solution to complex issues in the related field of coronavirus. However, whether coronavirus-related research becomes more interdisciplinary still needs corroboration. In this study, we investigate interdisciplinary status of the coronavirus-related fields via the COVID-19 Open Research Dataset (CORD-19). To this end, we calculate bibliometric indicators of interdisciplinarity and apply a co-occurrence analysis method. The results show that co-occurrence relationships between cited disciplines have evolved dynamically over time. The two types of co-occurrence relationships, Immunology and Microbiology & Medicine and Chemical Engineering & Chemistry, last for a long time in this field during 1990-2020. Moreover, the number of disciplines cited by coronavirus-related research increases, whereas the distribution of disciplines is uneven, and this field tends to focus on several dominant disciplines such as Medicine, Immunology and Microbiology, Biochemistry, Genetics and Molecular Biology. We also measure the disciplinary diversity of COVID-19 related papers published from January to December 2020; the disciplinary variety shows an upward trend, while the degree of disciplinary balance shows a downward trend. Meanwhile, the comprehensive index 2Ds demonstrates that the degree of interdisciplinarity in coronavirus field decreases between 1990 and 2019, but it increases in 2020. The results help to map the interdisciplinarity of coronavirus-related research, gaining insight into the degree and history of interdisciplinary cooperation.

Robust exceptional point of arbitrary order in coupled spinning cylinders.

Exceptional points (EPs), i.e., non-Hermitian degeneracies at which eigenvalues and eigenvectors coalesce, can be realized by tuning the gain/loss contrast of different modes in non-Hermitian systems or by engineering the asymmetric coupling of modes. Here we demonstrate a mechanism that can achieve EPs of arbitrary order by employing the non-reciprocal coupling of spinning cylinders sitting on a dielectric waveguide. The spinning motion breaks the time-reversal symmetry and removes the degeneracy of opposite chiral modes of the cylinders. Under the excitation of a linearly polarized plane wave, the chiral mode of one cylinder can unidirectionally couple to the same mode of the other cylinder via the spin-orbit interaction associated with the evanescent wave of the waveguide. The structure can give rise to arbitrary-order EPs that are robust against spin-flipping perturbations, in contrast to conventional systems relying on spin-selective excitations. In addition, we show that higher-order EPs in the proposed system are accompanied by enhanced optical isolation, which may find applications in designing novel optical isolators, nonreciprocal optical devices, and topological photonics.

Prediction Methods of Herbal Compounds in Chinese Medicinal Herbs.

Chinese herbal medicine has recently gained worldwide attention. The curative mechanism of Chinese herbal medicine is compared with that of western medicine at the molecular level. The treatment mechanism of most Chinese herbal medicines is still not clear. How do we integrate Chinese herbal medicine compounds with modern medicine? Chinese herbal medicine drug-like prediction method is particularly important. A growing number of Chinese herbal source compounds are now widely used as drug-like compound candidates. An important way for pharmaceutical companies to develop drugs is to discover potentially active compounds from related herbs in Chinese herbs. The methods for predicting the drug-like properties of Chinese herbal compounds include the virtual screening method, pharmacophore model method and machine learning method. In this paper, we focus on the prediction methods for the medicinal properties of Chinese herbal medicines. We analyze the advantages and disadvantages of the above three methods, and then introduce the specific steps of the virtual screening method. Finally, we present the prospect of the joint application of various methods.

Standard b-value versus low b-value diffusion-weighted MRI in renal cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: We sought to determine the comparative diagnostic performance of standard b-value (800-1000 s/mm2) versus low b-value (400-500 s/mm2) diffusion-weighted magnetic resonance imaging (DW-MRI) in the detection of renal cell carcinoma (RCC). METHOD: After a systematic review of the available literature, studies were included that reported b-values, used a histopathological reference standard, and allowed construction of 2 × 2 contingency tables for detection of RCC lesions using DW-MRI. In addition, a summary receiver operating characteristic (SROC) analysis was performed. RESULTS: Four articles that complied with all inclusion and exclusion criteria were selected for data extraction and analysis (n = 248 lesions in 266 patients). All four studies were high quality. Standard b-value DW-MRI displayed a pooled sensitivity of 0.59 (95% confidence interval (CI): 0.51-0.67) and a pooled specificity of 0.50 (95% CI: 0.30-0.70), while low b-value DW-MRI displayed a pooled sensitivity of 0.58 (95% CI: 0.48-0.63) and a pooled specificity of 0.23 (95% CI: 0.09-0.44). The SROC curve of standard b-value DW-MRI displayed an AUC of 0.61 and a Q*index of 0.59, while the SROC curve of low b-value DW-MRI displayed an AUC of 0.68 and a Q*index of 0.64. CONCLUSION: Standard b-value DW-MRI showed a superior specificity but an approximately equivalent sensitivity to low b-value DW-MRI in detecting RCC lesions in the kidney. However, low b-value DW-MRI displayed an overall superior diagnostic accuracy over standard b-value DW-MRI.

Leveraging ChatGPT to optimize depression intervention through explainable deep learning.

Introduction: Mental health issues bring a heavy burden to individuals and societies around the world. Recently, the large language model ChatGPT has demonstrated potential in depression intervention. The primary objective of this study was to ascertain the viability of ChatGPT as a tool for aiding counselors in their interactions with patients while concurrently evaluating its comparability to human-generated content (HGC). Methods: We propose a novel framework that integrates state-of-the-art AI technologies, including ChatGPT, BERT, and SHAP, to enhance the accuracy and effectiveness of mental health interventions. ChatGPT generates responses to user inquiries, which are then classified using BERT to ensure the reliability of the content. SHAP is subsequently employed to provide insights into the underlying semantic constructs of the AI-generated recommendations, enhancing the interpretability of the intervention. Results: Remarkably, our proposed methodology consistently achieved an impressive accuracy rate of 93.76%. We discerned that ChatGPT always employs a polite and considerate tone in its responses. It refrains from using intricate or unconventional vocabulary and maintains an impersonal demeanor. These findings underscore the potential significance of AIGC as an invaluable complementary component in enhancing conventional intervention strategies. Discussion: This study illuminates the considerable promise offered by the utilization of large language models in the realm of healthcare. It represents a pivotal step toward advancing the development of sophisticated healthcare systems capable of augmenting patient care and counseling practices.

Clinical application of the retrograde track method in reopening dysfunctional biliary stents.

Background: Biliary stent dysfunction is challenging to treat in clinic. The retrograde track method (RTM) has a promising clinical application in the reopening of dysfunctional biliary stents. This study aimed to evaluate the clinical value of the RTM in reopening dysfunctional biliary stents. Methods: From February 2013 to January 2020, 151 patients underwent percutaneous transhepatic biliary interventional procedures for reopening dysfunctional biliary stents at the First Affiliated Hospital of Zhengzhou University, and 25 patients (12 females, 13 males; mean age 63.12 years old) underwent the RTM after anterograde reopening dysfunction biliary stent failure. Technical success, clinical success, irradiation dose, procedure time, complications, and overall survival (OS) were recorded, and levels of total bilirubin (TBIL), direct bilirubin (DB), alanine aminotransferase (ALT), albumin (ALB), and carbohydrate antigen-199 (CA-199) were compared before treatment and 1 month after treatment. Results: The technical and clinical success rates were 100% and 96%, respectively, and the irradiation dose and procedure times were 774.07±330.80 mGy and 45.16±9.48 min, respectively. Two patients (8%) experienced major complications. The median OS was 10.73 months [95% confidence interval (CI): 9.37-12.09]. Compared with pretreatment values, the mean levels at 1 month after RTM administration for TBIL (189.47±59.20 vs. 44.65±16.12 µmol/L), DB (144.21±55.83 vs. 27.95±13.86 µmol/L), ALT (89.62±30.85 vs. 49.44±14.25 U/L), and CA-199 (584.59±269.82 vs. 176.76±100.68 U/mL) showed significant decreases, while that of ALB (36.32±2.05 vs. 40.22±1.95 g/L) showed a significant increase (all P values <0.05). Conclusions: RTM is an effective alternative treatment method when anterograde reopening of a dysfunctional biliary stent occurs.

Microstructure and Texture Evolution of Cu-Ni-P Alloy after Cold Rolling and Annealing.

The microstructure and texture evolution of Cu-Ni-P alloy after cold rolling and annealing at 500 °C was studied by electron backscattering diffraction (EBSD). The equiaxed grain is elongated and the dislocation density increases gradually after cold rolling. The grain boundaries become blurred and the structure becomes banded when the reduction in cold rolling reaches 95%. A typical rolling texture is formed with the increase in deformation amount in cold rolling. The deformation structure gradually disappeared and recrystallized new grains were formed after annealing at 500 °C. The recrystallization nucleation mechanism of Cu-Ni-P alloy at 60% reduction is mainly a bow nucleation mechanism. A shear band begins to form after annealing at 80% reduction. The shear band becomes the preferred nucleation location with the increase in reduction. Most adjacent recrystallized grains growing in the shear band have a twin relationship.

A novel technique to remove migrated esophageal stent under fluoroscopy.

PURPOSE: To evaluate the efficacy and safety of a novel technique for removal of migrated esophageal stent (MES) under fluoroscopy. METHODS: From January 2009 to April 2023, 793 patients with a dysphagia score of 3-4 underwent esophageal stenting at our center, and 25 patients (mean age: 70.06 years old; male/female: 15/10) underwent stent removal using "loop method" under fluoroscopy. The primary outcomes were technical success and complications. The secondary outcomes were procedure time, radiation exposure, biochemical indicators [white blood cell (WBC), hemoglobin (Hb), platelet (PLT), albumin (ALB), alanine transaminase (ALT), total bilirubin (TB), urea nitrogen (UN) and C-reactive protein] of pre- and post-treatment at 2 weeks. RESULTS: Technical success was 100% without major complications. The mean procedure time was (39.44 ± 9.28) minutes, which showed no statistical significance between benign (n = 5) and malignant (n = 20) group [(42.40 ± 8.85) vs (38.71 ± 9.46) mins, p > 0.05]. The mean radiation exposure was (332.88 ± 261.47) mGy, which showed no statistical significance between benign and malignant group [(360.74 ± 231.43) vs (325.92 ± 273.54) mGy, p > 0.05]. Pre- and post-procedure Hb [(114.46 ± 11.96) vs. (117.57 ± 13.12) g/L] and ALB [(42.26 ± 3.39) vs. (44.12 ± 3.77) g/L] showed significant difference (p < 0.05), while WBC, PLT, CRP, and ALT showed no significance (p > 0.05). CONCLUSION: Fluoroscopy-guided "Loop method" for MES removal is an effective and safe alternative technique.

Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

Efficacy and safety of raltitrexed-eluting CalliSpheres® bead transarterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma: a single-arm, prospective study.

Background: The most common loadable chemotherapeutic drugs in drug-eluting bead transarterial chemoembolization (DEB-TACE) include doxorubicin, epirubicin, etc. CalliSpheres® beads have exhibited efficient loadability and eluting characteristics for raltitrexed as well as in vitro and animal experiments. However, the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. Objectives: To assess the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage HCC. Design: The study was conducted as a single-arm prospective study. Methods: This study was a prospective, single-arm trial conducted between June 2019 and June 2022. CalliSpheres® beads loaded with raltitrexed were used in the DEB-TACE procedure. The follow-up lasted for at least 1 year or until death. The primary endpoint was overall survival (OS), and the secondary endpoints were time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: The 6-month ORR and disease control rates were 90.1% and 93.8%, respectively. The median OS was 33.0 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Child-Pugh class and bilobar disease occurrence were identified as independent OS predictors. The median TTP and PFS were 22.7 and 19.8 months, respectively. Eleven (11.5%) patients experienced at least one grade 3 AE, and serious AEs were reported in five participants (5.2%). No patient experienced grade 4 or 5 AEs. Conclusion: Raltitrexed-loaded DEB-TACE is feasible, safe, and effective in patients with intermediate-stage HCC. Trial registration: This trial was registered at www.chictr.org.cn under the identifier: 1900024097 on 25 June 2019.

Efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma The utility of raltitrexed-loaded CalliSphere® beads in drug-eluting bead transarterial chemoembolization (DEB-TACE) has been demonstrated in in vitro and animal experiments. However, its efficacy and safety in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. Hence, this study aimed to assess the efficacy and safety profiles of DEB-TACE for such patients. We discovered that raltitrexed-loaded DEB-TACE led to a 6-month ORR of 90.1%, a median OS of 33.0 months, a median TTP of 22.7 months, and a median PFS of 19.8 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Factors such as Child-Pugh class and bilobar disease occurrence were identified as independent predictors of OS. The study also showed acceptable safety profiles, with a low incidence of grade 3 adverse events and no grade 4 or 5 adverse events. The results indicated that raltitrexed-eluting CalliSpheres® beads for TACE can be a viable option for treating patients with intermediate-stage HCC.