Impact of blood pressure variability and cerebral small vessel disease: A systematic review and meta-analysis.

Importance: Abnormal blood pressure pattern is an independent risk factor for vascular events. Blood pressure variability can predict cardiovascular and cerebrovascular disease outcomes and is closely associated with the risk of cognitive impairment. However, the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers remains unclear. This study aimed to evaluate the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers. Data sources: We searched multiple databases, including Embase, Web of Science, PubMed, Cochrane Library, UpToDate, and World of Science, from their inception until November 27, 2023.Main Outcomes and Measures: A meta-analysis of 19 observational studies involving 14519 participants was performed. Findings: ①Systolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and lacunar infarction; ② Diastolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and cerebral microbleeds; ③ Non-dipping patterns were correlated with white matter hyperintensities and lacunar infarction. ④ Reverse-dipping patterns were significantly correlated with white matter hyperintensities and cerebral microbleeds. Conclusions: and Relevance: Blood pressure variability correlates with neuroimaging markers of cerebral small vessel disease and its burden. Hence, early monitoring and intervention of blood pressure variability may be essential for the early diagnosis, prevention and treatment of cerebral small vessel disease.

Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties. RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level. CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

Long-Term High-Fat Diet Impairs AQP4-Mediated Glymphatic Clearance of Amyloid Beta.

As a risk factor for Alzheimer's disease (AD), studies have demonstrated that long-term high-fat diet (HFD) could accelerate the deposition of amyloid beta (Aß) in the brain. The glymphatic system plays a critical role in Aß clearance from the brain. However, studies investigating the effects of long-term HFD on glymphatic function have reported paradoxical outcomes, and whether glymphatic dysfunction is involved in the disturbance of Aß clearance in long-term HFD-fed mice has not been determined. In the present study, we injected fluorescently labeled Aß into the hippocampus and found that Aß clearance was decreased in HFD-fed mice. We found that long-term HFD-fed mice had decreased glymphatic function by injecting fluorescent tracers into the cisterna magna and corpus striatum. In long-term HFD-fed mice, aquaporin-4 (AQP4) polarization in the cortex was disrupted, and glymphatic clearance activity was positively correlated with the AQP4 polarization index. In HFD-fed mice, the disturbance of Aß clearance from the hippocampus was exacerbated by TGN-020, a specific inhibitor of AQP4, whereas TGN-073, an enhancer of AQP4, ameliorated it. These findings suggest that long-term HFD disrupts Aß clearance by inhibiting AQP4-mediated glymphatic function. The underlying mechanism may involve the disruption of AQP4 polarization.

Nonlinearly coupled electro-osmotic flow in variable charge soils.

Electro-osmosis has been valued as a promising technology to enhance the dewatering of waste sludge, stabilization and environmental remediation of soils with low permeability. However, the coefficient of electro-osmotic permeability (keo) is commonly taken as constant value which is particularly not the case in variable charge soil. As a result, the nonlinearity of the electro-osmotic flow (EOF) and the direction reverse could not be interpreted. Herein, the electro-chemical parameters were monitored in electro-osmotic experiment with natural variable charge soil. It was observed that evolutions showed significant nonlinear behavior and were correlated. The comprehensive Zeta potential model proposed by the authors was applied to simulate the nonlinear keo induced by the variable pH and electrolyte concentration. The agreement between tested and simulated flow rate variation and excess pore water pressure distribution demonstrated the reliability of the theory. The error rate of the simulations through coupling nonlinear keo and voltage gradient Ex was reduced to 29.4% from 381.9% of calculations with constant parameters. The direction reverse of EOF was innovatively interpreted. Hence, the numerical model would act as a useful tool to connect these electro-chemical parameters and provide guidance to evaluate contributions of commonly used pH conditioning measurements.

First report of Fusarium humuli causing stem spots in Nicotiana tabacum L in China.

Tobacco is one of the most important economic crops in China. Disease is one of the main factors affecting the quality of tobacco production (Cai et al. 2022). Stem spot disease of tobacco was observed in the Planting Demonstration Garden in Chang Ning (26°37N; 112° 31E), Hunan Province of China, from May to June 2023. The disease seriously retarded tobacco growth and the incidence rate was about 30-50% of the plants(Yun Yan 87). Most of infected tobacco had black spots on the stems, and the spots expanded and joined together quickly, while many stems turned black and withered. For pathogen isolation, symptomatic stem samples were collected and disinfected with 75% ethanol for 30 s and 2% sodium hypochlorite for 1 minute, followed by rinsing with sterile distilled water three times. Subsequently, small pieces (5 × 5 mm) of diseased tissues were placed on potato dextrose agar (PDA) and incubated in the dark at 25 °C for 24 h to 36 h. The emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method(Yu et al. 2022). In total, 16 cultures with the same appearance were isolated from 30 disease spots on the stem. Strain coded as hnxryc2 was randomly selected for identification. After culturing in PDA for 7 days, white and dense colonies wereobserved with a mean radial growth rate of 6.4 mm/day. The strain cultured 10 days on SNA. Morphological observations were made on 10-day-old culture on SNA medium, and macroconidia were sickle-shaped and slightly curved, with 3-5 septa (2.32-7.00 µm × 0.53-1.17 µm, n = 50), neither microconidia nor chlamydospores were observed. These morphological characteristics were consistent with the description of Fusarium humuli (Wang et al. 2019, Li et al. 2023). Furthermore, primers ITS1/ITS4, EF728F/EF986R, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR(Xie et al. 2023) were used to amplify the ITS region, EF-1α, RPB1, and RPB2 from strain hnxryc2, respectively. The sequence alignment of hnxryc2 with the NCBI database and FUSARIOID-ID shows the following results: The sequence of ITS region(GenBank accession number PP543715) was 100% identical to these of Fusarium sp. (MN428026.1), the sequences of EF-1α, RPB1, and RPB2 of strain hnxryc2(GenBank accession numbersOR257586, OR326856 and OR257587 respectively) were 99% to 100% identical to these of F. humuli (GenBank accession numbers MK289578.1, MZ824672.1 and MZ824673.1, respectively). Then a phylogenetic tree based on ITS region, EF-1α, and RPB2 sequences was constructed (Kroon et al. 2004). The strain hnxryc2 was more closely related to F. humuli (CGMCC3.19374 GenBank accession nos. MK280845.1, MK289570.1 and MK289724.1, respectively), with bootstrap values 88%. Pathogenicity tests were performed on detached stems of tobacco and potted plants. Wounded stems were inoculated with conidial suspensions (100 µL, 1×107 spores/mL), and the controls were inoculated with sterile water (Xu et al. 2023). The inoculated detached stems were kept in humid chambers (Zhong et al., 2019), each treatment was given a 12h/12h light/dark cycle at 25°C. Deep black spots were observed for 3 days after inoculation. After 9 days, typical symptoms similar to the original diseased plants in the field were found on all inoculated stems, while the control stems did not exhibit any symptoms. Pathogenicity assays were repeated thrice. The pathogen F. humuli was successfully reisolated from the stem of inoculated samples showing symptoms. To our knowledge, this is the first report of F. humuli inducing stem spot on tobacco in China. Since F. humuli is a common pathogenic fungus that infects different plant species, more attention should be paid to its prevalence in tobacco, and the potential risk of a disease outbreak in other provinces of China.

Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Residue-Free Orally Administered Drug Carrier Based on a Porous Aromatic Framework for Efficient Multisite Treatment.

Nowadays, oral medications are the primary method of treating disease due to their convenience, low cost, and safety, without the need for complex medical procedures. To maximize treatment effectiveness, almost all oral medications utilize drug carriers, such as capsules, liposomes, and sugar coatings. However, these carriers rely on dissolution or fragmentation to achieve drug release, which leads to drugs and carriers coabsorption in the body, causing unnecessary adverse drug reactions, such as nausea, vomiting, abdominal pain, and even death caused by allergy. Therefore, the ideal oral drug carrier should avoid degradation and absorption and be totally excreted after drug release at the desired location. Herein, a gastrointestinally stable oral drug carrier based on porous aromatic framework-1 (PAF-1) is constructed, and it is modified with famotidine (a well-known gastric drug) and mesalazine (a well-known ulcerative colitis drug) to verify the excellent potential of PAF-1. The results demonstrate that PAF-1 can accurately release famotidine in stomach, mesalazine in the intestine, and finally be completely excreted from the body without any residue after 12 h. The use of PAF materials for the construction of oral drug carriers with no residue in the gastrointestinal tract provides a new approach for efficient disease treatment.

A near-resonant excitation strategy to achieve ultra-low threshold GaN polariton lasing.

A near-resonant excitation strategy is proposed and implemented in a 4-µm-thick GaN microcavity to realize an exciton-polariton condensate/lasing with low threshold. Strong exciton-photon coupling is demonstrated, and polariton lasing is realized with an ultra-low threshold excitation power density of about 13.3 W/cm2 at room temperature. Such an ultra-low threshold is ascribed to the implementation of the near-resonant optical excitation strategy, which enables acceleration of the exciton and polariton relaxation and suppression of the heat generation in the cavity, thereby reducing the energy loss and enhance the cavity excitation efficiency.

Early warning of atrial fibrillation using deep learning.

Atrial fibrillation (AF), the most prevalent cardiac rhythm disorder, significantly increases hospitalization and health risks. Reverting from AF to sinus rhythm (SR) often requires intensive interventions. This study presents a deep-learning model capable of predicting the transition from SR to AF on average 30.8 min before the onset appears, with an accuracy of 83% and an F1 score of 85% on the test data. This performance was obtained from R-to-R interval signals, which can be accessible from wearable technology. Our model, entitled Warning of Atrial Fibrillation (WARN), consists of a deep convolutional neural network trained and validated on 24-h Holter electrocardiogram data from 280 patients, with 70 additional patients used for testing and further evaluation on 33 patients from two external centers. The low computational cost of WARN makes it ideal for integration into wearable technology, allowing for continuous heart monitoring and early AF detection, which can potentially reduce emergency interventions and improve patient outcomes.

Experimental data simulating lithium battery charging and discharging tests under different external constraint pressure conditions.

In this paper, the GSP655060Fe soft pack lithium-ion battery with a capacity of 1600 mAh is utilized, employing lithium iron phosphate as the positive electrode and graphite as the negative electrode. In order to comprehensively evaluate the performance of lithium batteries under the conditions of multi-application scenarios, the operating conditions of the battery were simulated under various external confinement pressures of 300 N, 400 N, 500 N, and 600 N, respectively, and the ambient temperatures of 10 ℃, 25 ℃, and 40 ℃, respectively, were controlled to thoroughly test the battery. One charge/discharge test was conducted on six batteries of the same model at multiplicities of 0.5 C, 1 C, 1.5 C, and 2 C, respectively. To ensure the accuracy and reliability of the experimental data, a Battery comprehensive tester Neware BTS-5V12A was utilized, which possesses high-precision voltage and current measurement capabilities with an error rate of only 0.05 %. This data plays an important role in battery research and development, new energy vehicles, electronic products, and other fields.

Intermittent electrostimulation-modified direct interspecies electron transfer for enhanced methanogenesis in anaerobic digestion of sulfate-rich wastewater.

Methane recovery and organics removal in sulfate (SO42-)-rich wastewater anaerobic digestion are hindered by electron competition between methanogenesis and sulfidogenesis. Here, intermittently electrostimulated bioelectrodes were developed to facilitate direct interspecies electron transfer (DIET)-driven syntrophic methanogenesis, increasing substrate competition among methanogenic archaea (MA). By optimising the electrochemical environment, MA was able to employ electron transfer more efficiently than sulfate-reducing bacteria (SRB), resulting in significant methane accumulation (58.1 ± 1.0 mL-CH4/m3reactor) and COD removal (90.5 ± 0.5 %) at lower COD/SO42- ratio. Intermittent electrostimulation improved the metabolic pathway for electroactive bacteria to utilize acetate and direct electrons to electrotrophic MA, decreasing SRB abundance and affecting the sulfate reduction pathway. Intermittently electrostimulated biofilms significantly increased gene levels of key enzymes in electron transport for cytochrome and e-pili biosynthesis, crucial for DIET, demonstrating enhanced DIET-driven syntrophic methanogenesis. This study provides a strategic approach to optimize methanogenesis in sulfate-rich wastewater anaerobic digestion.

Promotion of stem cell-like phenotype of lung adenocarcinoma by FAM83A via stabilization of ErbB2.

Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.

PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina.

BACKGROUND: Inherited retinal dystrophies (IRDs) are a group of debilitating visual disorders characterized by the progressive degeneration of photoreceptors, which ultimately lead to blindness. Among the causes of this condition, mutations in the PCYT1A gene, which encodes the rate-limiting enzyme responsible for phosphatidylcholine (PC) de novo synthesis via the Kennedy pathway, have been identified. However, the precise mechanisms underlying the association between PCYT1A mutations and IRDs remain unclear. To address this knowledge gap, we focused on elucidating the functions of PCYT1A in the retina. RESULTS: We found that PCYT1A is highly expressed in Müller glial (MG) cells in the inner nuclear layer (INL) of the retina. Subsequently, we generated a retina-specific knockout mouse model in which the Pcyt1a gene was targeted (Pcyt1a-RKO or RKO mice) to investigate the molecular mechanisms underlying IRDs caused by PCYT1A mutations. Our findings revealed that the deletion of Pcyt1a resulted in retinal degenerative phenotypes, including reduced scotopic electroretinogram (ERG) responses and progressive degeneration of photoreceptor cells, accompanied by loss of cells in the INL. Furthermore, through proteomic and bioinformatic analyses, we identified dysregulated retinal fatty acid metabolism and activation of the ferroptosis signalling pathway in RKO mice. Importantly, we found that PCYT1A deficiency did not lead to an overall reduction in PC synthesis within the retina. Instead, this deficiency appeared to disrupt free fatty acid metabolism and ultimately trigger ferroptosis. CONCLUSIONS: This study reveals a novel mechanism by which mutations in PCYT1A contribute to the development of IRDs, shedding light on the interplay between fatty acid metabolism and retinal degenerative diseases, and provides new insights into the treatment of IRDs.

Deciphering the Catalytic Mechanism of Peroxidase-like Activity of Iron Sulfide Nanozymes.

Iron sulfide nanomaterials represented by FeS2 and Fe3S4 nanozymes have attracted increasing attention due to their biocompatibility and peroxidase-like (POD-like) catalytic activity in disease diagnosis and treatments. However, the mechanism responsible for their POD-like activities remains unclear. Herein, taking the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) by H2O2 on FeS2(100) and Fe3S4(001) surfaces, the catalytic mechanism was investigated in detail using density functional theory (DFT) calculations and experimental characterizations. Our experimental results showed that the catalytic activity of FeS2 nanozymes was significantly higher than that of Fe3S4 nanozymes. Our DFT calculations indicated that the surface iron ions of iron sulfide nanozymes could effectively catalyze the production of HO• radicals via the interactions between Fe 3d electrons and the frontier orbitals of H2O2 in the range of -10 to 5 eV. However, FeS2 nanozymes exhibited higher POD-like activity due to the surface Fe(II) binding to H2O2, forming inner-orbital complexes, which results in a larger binding energy and a smaller energy barrier for the base-like decomposition of H2O2. In contrast, the surface iron ions of Fe3S4 nanozymes bind to H2O2, forming outer-orbital complexes, which results in a smaller binding energy and a larger energy barrier for the base-like decomposition of H2O2. The charge transfer analysis showed that FeS2 nanozymes transferred 0.12 e and Fe3S4 nanozymes transferred 0.05 e from their surface iron ions to H2O2, respectively. The simulations were consistent with the experimental observations that the FeS2 nanozymes had a greater affinity for H2O2 compared to that of Fe3S4 nanozymes. This work provides a theoretical foundation for the rational design and accurate preparation of iron sulfide functional nanozymes.

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy.

Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.

Analysis of risk factors for the sigmoid stoma complications in patients after abdominoperineal resection surgery: An observational study.

To analyze the risk factors for intraperitoneal sigmoid stoma complications after abdominoperineal resection (APR) surgery to guide clinical practice. Patients who were diagnosed with rectal cancer and underwent APR surgery from June 2013 to June 2021 were retrospectively enrolled. The characteristics of the stoma complication group and the no stoma complication group were compared, and univariate and multivariate logistic analyses were employed to identify risk factors for sigmoid stoma-related complications. A total of 379 patients who were diagnosed with rectal cancer and underwent APR surgery were enrolled in this study. The average age of the patients was 61.7 ±â€…12.1 years, and 226 (59.6%) patients were males. Patients in the short-term stoma complication group were younger (55.7 vs 62.0, P < .05) and had a more advanced tumor stage (P < .05). However, there was no significant difference between the long-term stoma complication group and the no stoma complication group. Multivariate logistic regression analysis revealed that operation time was an independent risk factor (P < .05, OR = 1.005, 95% CI = 1.000-1.010) for short-term stoma complications. Both the short-term and long-term stoma complication rates in our institution were low. A longer operation time was an independent risk factor for short-term stoma complications after APR surgery.

The urinary microbiota composition and functionality of calcium oxalate stone formers.

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.

Clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 seed implantation for the treatment of superficial soft tissue metastasis: a 12-year retrospective analysis.

BACKGROUND: Superficial soft tissue metastasis (S-STM) of malignant tumors is uncommon and often brings great pain to patients. However, current treatment options are limited. The purpose of this study was to explore the clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 (125I) seed implantation (RISI) for the treatment of S-STM. METHODS: We retrospectively evaluated 132 patients with S-STM who received RISI between June 2010 and July 2022. Local tumor progression-free survival (ltPFS), tumor response, pain control and complication were analyzed. The independent factors affecting ltPFS were screened out using a layered Cox proportional hazards model. RESULTS: The median follow-up time was 8.3 months (interquartile range [IQR], 4.5-15.3 months). The objective response rate (ORR) was 81.8%. The median ltPFS was 9.1 (95% CI: 6.6, 11.6) months. The Cox proportional hazard regression model revealed that the independent factors influencing ltPFS included KPS score, primary tumor, metastases, boundary, density and postoperative D90 (All P < 0.05). After RISI, the rate of pain relief was 92.3%. 66 (84.6%) patients reported pain marked relief, and 6 (7.7%) experienced pain moderate relief. No severe adverse events associated with RISI were observed during follow-up. CONCLUSIONS: CT-guided RISI was associated with high local control and pain relief without severe adverse events and should be considered as a reliable palliative treatment modality for S-STM. TRIAL REGISTRATION: Trial registration Retrospectively registered.

Dynamic behavior of electro-osmosis in variable charge soils: Insights on termination and direction reversal.

Electro-osmosis offers an effective method for dewatering and remediating low permeability soil. Long-term observations on nonlinear behavior of electro-osmosis and the influencing factors are not commonly reported. Connection between cessation and direction reversal of electro-osmotic flow (EOF), and the evolution of electro-chemical parameters inside of the soil mass thus remains unclear. The dynamic response of EOF in variable charge soil could be significant, whereas the investigations on which are currently lacking. A series of electro-osmotic experiments were performed with two natural variable charge soils. The results indicated that initial electro-osmotic rate was positively proportional to electric current and initial electrical conductivity of the pore fluid, which could be explained by the ion migration model. The dynamic evolution of electro-osmotic rate and electro-chemical parameters corresponding to the solute and pH conditionings at the electrode compartments demonstrated that: 1) coupling effects of non-uniform distribution of voltage gradient and pH determined the magnitude and direction of EOF rate; 2) compared to the final pHIEP value, the bigger, close and smaller values of the novel index "voltage gradient weighed mean of spatial pH″ represented the forward, terminated and reversed EOF respectively; 3) the classical Helmholtz-Smoluchowski model are proved to be more applicable interpreting the coupled nonlinearity of electro-osmosis during the later steady phase. This work would facilitate future research for a comprehensive electro-osmotic model, and provide guidance to condition the initial and boundary conditions in application of electro-osmotic dewatering and electrokinetic remediation.