Enterprise stents for the treatment of symptomatic non-acute intracranial artery stenosis disease: safety and efficiency evaluation.

BACKGROUND: Enterprise stent was approved for the treatment of wide-necked intracranial aneurysms. However, it has been widely used in the endovascular treatment of intracranial artery stenosis, which is still controversial. The purpose of this study was to evaluate the safety and efficiency of the Enterprise stent in the endovascular treatment of intracranial artery stenosis disease. METHODS: We conducted a retrospective case series of 107 patients with intracranial artery stenosis who received Enterprise stent implantation at Nanjing Drum Tower Hospital from January 2020 to December 2022. The rates of recanalization, perioperative complications, in-stent restenosis at 3-12 months and stroke recurrence were assessed for endovascular treatment. RESULTS: A total of 107 individuals were included in this study, 88 were followed up, and 19 (17.8%) patients were lost to follow-up. The operation success rate was 100%, During the procedure,4（3.7%）patients had vasospasm, and 2(1.9%) patients showed symptomatic bleeding. The overall perioperative complication rate was 5.6%, including 2.8% distal artery embolism, 0.9% in-stent thrombosis, and 1.9% symptomatic bleeding. 88 (82.2%) patients were followed up from 3 to 12 months, of whom 12 (13.6%) had in-stent restenosis, 4 (4.7%) recurrent strokes and 2 died of pulmonary infection caused by COVID-19. Patients were divided into 3 groups according to the cerebral artery, including the middle cerebral artery group, internal carotid artery group, and vertebrobasilar artery group. CONCLUSIONS: In this study, the placement of the Enterprise stent in patients with symptomatic non-acute intracranial stenosis was successful. However, the occurrence of periprocedural and long-term complications after stenting remains of high concern.

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model.

Knee osteoarthritis (KOA) usually leads to quadriceps femoris atrophy, which in turn can further aggravate the progression of KOA. Curcumin (CUR) has anti-inflammatory and antioxidant effects and has been shown to be a protective agent for skeletal muscle. CUR has been shown to have a protective effect on skeletal muscle. However, there are no studies related to whether CUR improves KOA-induced quadriceps femoris muscle atrophy. We established a model of KOA in rats. Rats in the experimental group were fed CUR for 5 weeks. Changes in autophagy levels, reactive oxygen species (ROS) levels, and changes in the expression of the Sirutin3 (SIRT3)-superoxide dismutase 2 (SOD2) pathway were detected in the quadriceps femoris muscle of rats. KOA led to quadriceps femoris muscle atrophy, in which autophagy was induced and ROS levels were increased. CUR increased SIRT3 expression, decreased SOD2 acetylation and ROS levels, inhibited the over-activation of autophagy, thereby alleviating quadriceps femoris muscle atrophy and improving KOA. CUR has a protective effect against quadriceps femoris muscle atrophy, and KOA is alleviated after improvement of quadriceps femoris muscle atrophy, with the possible mechanism being the reduction of ROS-induced autophagy via the SIRT3-SOD2 pathway.

Dual-Probe SERS Nanosensor: A Promising Approach for Sensitive and Ratiometric Detection of Glucose in Clinical Settings.

Diabetes is a major global health concern, with millions of annual deaths. Monitoring glucose levels is vital for clinical management, and urine samples offer a noninvasive alternative to blood samples. Optical techniques for urine glucose sensing have gained notable traction due to their cost-effectiveness and portability. Among these methods, surface-enhanced Raman spectroscopy (SERS) has attracted considerable attention thanks to its remarkable sensitivity and multiplexing capabilities. However, challenges remain in achieving reliable quantification through SERS. In this study, an alternative approach is proposed to enhance quantification involving the use of dual probes. Each probe is encoded with unique SERS signatures strategically positioned in the biologically silent region. One probe indicates the glucose presence, while the other acts as an internal reference for calibration. This setup enables ratiometric analysis of the SERS signal, directly correlating it with the glucose concentration. The fabrication of the sensor relies on the prefunctionalization of Fe sheets using an aryl diazonium salt bearing a -C≡CH group (internal reference), followed by the immobilization of Ag nanoparticles modified with an aryl diazonium salt bearing a -B(OH)2 group (for glucose capture). A secondary probe bearing a -B(OH)2 group on one side and a -C≡N group on the other side enables the ratiometric analysis by forming a sandwich-like structure in the presence of glucose (glucose indicator). Validation studies in aqueous solutions and artificial urine demonstrated the high spectral stability and the potential of this dual-probe nanosensor for sensitive glucose monitoring in clinical settings.

Hsa_circ_0101050 accelerates the progression of Colon cancer by targeting the miR-140-3 p/MELK axis.

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of colon cancer (CC). This study aimed to examine the role of a new circRNA circ_0101050 in CC. METHODS: Dual-luciferase reporter and RNA immunoprecipitation analyses were performed to validate the target relationships among maternal embryonic leucine zipper kinase (MELK), microRNA (miR)-140-3 p, and circ_0101050. Expression levels were calculated using western blotting and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blotting was performed to evaluate the relative expression of Bcl-2 and Bax proteins to determine cell death. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to determine the proliferative potential of CC cells. The migration rate of CC cells was evaluated using wound healing assays. Tumor formation tests were performed to determine the effect of circ_0101050 on tumor development in vivo. RESULTS: Elevated levels of circ_0101050 and MELK were observed in CC. By inhibiting circ 0,101,050 or MELK, CC cell proliferation and migration were inhibited, but CC cell apoptosis was promoted. Silencing circ_0101050 also inhibited CC growth in vivo. We also found that miR-140-3 p was downregulated, which alleviated the repressive effects of circ_0101050 knockdown on proliferating and migrating CC cells, as well as the stimulating effect on apoptosis. In addition, the absence of MELK alleviated the effects of miR-140-3 p downregulation, which enhanced CC cell malignancy. CONCLUSIONS: Circ_0101050 exacerbates malignant phenotypes in CC by targeting the miR-140-3 p/MELK axis. These findings suggested that the circ_0101050/miR-140-3 p/MELK network may be a prospective target for CC treatment.

Na/N Co-doped Seaweed Biochar Composite for Efficient Removal of Aqueous Pb(II) and Cu(II).

Pollution from harmful heavy metal ions such as Pb(II) and Cu(II) is causing serious environmental and health problems. In this study, Sodium and nitrogen co-doped porous carbon material (Na/NABc) was successfully prepared from seaweed, sodium hydroxide, and dicyandiamide. The experimental results showed that Na/NABc is an excellent adsorbent for the effective removal of Pb(II) and Cu(II) from water bodies. Specifically, 99.8% of Pb(II) and 64.6% Cu(II) (100 mg/L) were removed within 12 h using 10 mg Na/NABc(10%) at 25 °C. The adsorption of Pb(II) and Cu(II) in aqueous solution by Na/NABc(10%) was efficient and rapid in the first stage. The theoretical maximum removal capacities of Na/NABc for Pb(II) and Cu(II) were 959.6 and 299.1 mg/g, respectively. Pb(II) and Cu(II) ions were adsorbed quickly in the first 60 min, and the kinetics data were generally consistent with a pseudo-second-order model. Na/NABc(10%) had a large distribution coefficient for Pb(II) (8.38 L/mg) and Cu(II) (1.17 L/mg). The possible mechanisms were precipitation, Ion exchange, and surface complexation. The removal rate can reach about 70% after five cycles, and the release of sodium meets the standard. The results of this study demonstrate the potential applicability of Na/NABc(10%) for adsorption of heavy metals from aqueous solution.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study.

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Evaluation of rural vitality and development types in mountainous areas of southwestern China: A case study of Wuxi County, Chongqing.

Protecting and stimulating rural vitality is a critical step towards driving rural revitalization and development; This study outlined the application of a measurement system that indexes rural vitality levels at the township scale and evaluates rural vitality in terms of potential regeneration, survivability, and development. This study combined the CRITIC weighting method, the TOPSIS pros and cons solution-distance method, and a vertical-horizontal comparison method to evaluate the rural vitality of 30 townships in Wuxi County, Chongqing. Using these results, this study divided the townships according to their type of rural development. A natural breakpoint method was used to visualize the spatial pattern of rural development levels.The research showed that: (1) The average value of the composite score of rural vitality in Wuxi County is 0.342, and more than half of the townships' composite vitality values are lower than the average value of the overall vitality, which leads to the conclusion that the overall level of rural vitality is low; (2) the comprehensive level of rural vitality in Wuxi County decreased from southwest to northeast, and showed local variations; (3) the degree of development within the study area was categorized as either dominant, comprehensive, or polarized, developmental deficiency type. This research argued that promoting the development of rural vitality in different villages requires careful scientific planning, detailed knowledge of individual geographic characteristics, and a clear rural development path that spans a range of spatial scales. Specific and specialized rural development strategies are thus required for each type of development.

Notoginsenoside R1 alleviates cerebral ischemia/reperfusion injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway through microbiota-gut-brain axis.

BACKGROUND: Ischemic stroke (IS) ranks as the second common cause of death worldwide. However, a narrow thrombolysis timeframe and ischemia-reperfusion (I/R) injury limits patient recovery. Moreover, anticoagulation and antithrombotic drugs do not meet the clinical requirements. Studies have demonstrated close communication between the brain and gut microbiota in IS. Notoginsenoside R1 (NG-R1), a significant component of the total saponins from Panax notoginseng, has been demonstrated to be effective against cerebral I/R injury. Total saponins have been used to treat IS in Chinese pharmacopoeia. Furthermore, previous research has indicated that the absorption of NG-R1 was controlled by gut microbiota. STUDY DESIGN: This study aimed to access the impact of NG-R1 treatment on neuroinflammation and investigate the microbiota-related mechanisms. RESULTS: NG-R1 significantly reduced neuronal death and neuroinflammation in middle cerebral artery occlusion/reperfusion (MCAO/R) models. 16S rRNA sequencing revealed that NG-R1 treatment displayed the reversal of microbiota related with MCAO/R models. Additionally, NG-R1 administration attenuated intestinal inflammation, gut barrier destruction, and systemic inflammation. Furthermore, microbiota transplantation from NG-R1 exhibited a similar effect in the MCAO/R models. CONCLUSION: In summary, NG-R1 treatment resulted in the restoration of the structure of the blood-brain barrier (BBB) and reduction in neuroinflammation via suppressing the stimulation of astrocytes and microglia in the cerebral ischemic area. Mechanistic research demonstrated that NG-R1 treatment suppressed the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signaling pathway in both the ischemic brain and colon. NG-R1 treatment enhanced microbiota dysbiosis by inhibiting the TLR4 signaling pathway to protect MCAO/R models. These findings elucidate the mechanisms by which NG-R1 improve stroke outcomes and provide some basis for Panax notoginseng saponins in clinical treatment.

Identification and neuroprotective properties of NA-184, a calpain-2 inhibitor.

Our laboratory has shown that calpain-2 activation in the brain following acute injury is directly related to neuronal damage and the long-term functional consequences of the injury, while calpain-1 activation is generally neuroprotective and calpain-1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain-2 inhibitor, referred to as C2I, enhanced long-term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we generated about 130 analogs of C2I and tested them in a number of in vitro and in vivo assays. These led to the identification of two interesting compounds, NA-112 and NA-184. Further analyses indicated that NA-184, (S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide, selectively and dose-dependent inhibited calpain-2 activity without evident inhibition of calpain-1 at the tested concentrations in mouse brain tissues and human cell lines. Like NA-112, NA-184 inhibited TBI-induced calpain-2 activation and cell death in mice and rats, both male and females. Pharmacokinetic and pharmacodynamic analyses indicated that NA-184 exhibited properties, including stability in plasma and liver and blood-brain barrier permeability, that make it a good clinical candidate for the treatment of TBI.

Biomimetic MicroRNAs-Selenium-Nanocomposites for Targeted and Combined Hyperlipidemia Therapy.

Hyperlipidemia is considered as a high-risk factor for leading to coronary heart disease. MicroRNA-148a-3p (miR-148a-3p) inhibitor is a potential therapeutic target to bind low-density lipoprotein cholesterol receptors (LDLR) for decreasing the levels of low-density lipoprotein cholesterol in plasma. However, the therapeutic effects are not ideal in the clinical translation of nucleic acids treatment, owing to the short circulation time in vivo. Therefore, a platelet membrane (PM) cloaks Se nanoparticles (SeNPs) delivery system with chitosan (CS) modifies and miR-148a-3p inhibitors encapsulated is designed (PM/CS-SeNPs/miR). The PM/CS-SeNPs/miR shows a uniform shell-core structure with a particle size of ≈90 nm. Co-delivering miR-148a-3p inhibitors and Se effectively alleviate hyperlipidemia via LDLR pathway and Toll-Like Receptor 4 (TLR-4)/NF-κB signaling pathway, respectively. Furthermore, coated by PM, PM/CS-SeNPs/miR successfully prolong circulation time to 48 h in vivo and quickly target to liver with no toxicity. This dual combination therapy with miRNAs and Se based on nanoparticles targeted delivery presents a high-performance strategy for precise hyperlipidemia treatment.

Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity.

Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival. Notably, PRMT9 inhibition promoted DNA damage and activated cyclic GMP-AMP synthase, which underlies the type I IFN response. Genetically activating cyclic GMP-AMP synthase in AML cells blocked leukemogenesis. We also report synergy of a PRMT9 inhibitor with anti-programmed cell death protein 1 in eradicating AML. Overall, we conclude that PRMT9 functions in survival and immune evasion of both LSCs and non-LSCs; targeting PRMT9 may represent a potential anticancer strategy.

Gut microbiota and cognitive performance: A bidirectional two-sample Mendelian randomization.

PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Simulations of Functional Motions of Super Large Biomolecules with a Mixed-Resolution Model.

Many large protein machines function through an interplay between large-scale movements and intricate conformational changes. Understanding functional motions of these proteins through simulations becomes challenging for both all-atom and coarse-grained (CG) modeling techniques because neither approach alone can readily capture the full details of these motions. In this study, we develop a multiscale model by employing the popular MARTINI CG model to represent a heterogeneous environment and structurally stable proteins and using the united-atom (UA) model PACE to describe proteins undergoing subtle conformational changes. PACE was previously developed to be compatible with the MARTINI solvent and membrane. Here, we couple the protein descriptions of the two models by directly mixing UA and CG interaction parameters to greatly simplify parameter determination. Through extensive validations with diverse protein systems in solution or membrane, we demonstrate that only additional parameter rescaling is needed to enable the resulting model to recover the stability of native structures of proteins under mixed representation. Moreover, we identify the optimal scaling factors that can be applied to various protein systems, rendering the model potentially transferable. To further demonstrate its applicability for realistic systems, we apply the model to a mechanosensitive ion channel Piezo1 that has peripheral arms for sensing membrane tension and a central pore for ion conductance. The model can reproduce the coupling between Piezo1's large-scale arm movement and subtle pore opening in response to membrane stress while consuming much less computational costs than all-atom models. Therefore, our model shows promise for studying functional motions of large protein machines.

Evaluation of the Effect of CaO on Hydrogen Production by Sorption-Enhanced Steam Methane Reforming.

The effect of heat released during CaO adsorption on sorption-enhanced steam methane reforming for hydrogen production is insufficiently understood. On this basis, Aspen Plus is used to study the effect of steam methane reforming on hydrogen production without/with CaO. At 700 °C and an O2 inflow of 7 mol/h, the molar flow and molar percentages of H2 are 20.62 and 67.35%. After adding CaO, at 700 °C with 4.5 mol/h of CaO, the heat release of CaO adsorption is 1.32 MJ/h, and the O2 inflow reduces to 4.3 mol/h. The molar flow and molar percentage of H2 are 22.80 mol/h and 85.94%. When 1.2 mol/h CH4 is combusted for CaCO3 decomposition in the calciner, regenerated CaO is transferred to the reforming reactor for calcium cycling, which consumes 2.4 mol/h of O2. For the entire cycle, 6.7 mol/h of O2.

Rapid discrimination between clinical Clostridioides difficile infection and colonization by quantitative detection of TcdB toxin using a real-time cell analysis system.

Objectives: It is important to accurately discriminate between clinical Clostridioides difficile infection (CDI) and colonization (CDC) for effective antimicrobial treatment. Methods: In this study, 37 stool samples were collected from 17 CDC and 20 CDI cases, and each sample were tested in parallel through the real-time cell analysis (RTCA) system, real-time PCR assay (PCR), and enzyme-linked immunosorbent assay (ELISA). Results: RTCA-measured functional and toxical C. difficile toxin B (TcdB) concentrations in the CDI group (302.58 ± 119.15 ng/mL) were significantly higher than those in the CDC group (18.15 ± 11.81 ng/mL) (p = 0.0008). Conversely, ELISA results revealed no significant disparities in TcdB concentrations between the CDC (26.21 ± 3.57 ng/mL) and the CDI group (17.07 ± 3.10 ng/mL) (p = 0.064). PCR results indicated no significant differences in tcdB gene copies between the CDC (774.54 ± 357.89 copies/µL) and the CDI group (4,667.69 ± 3,069.87 copies/µL) (p = 0.407). Additionally, the functional and toxical TcdB concentrations secreted from C. difficile isolates were measured by the RTCA. The results from the CDC (490.00 ± 133.29 ng/mL) and the CDI group (439.82 ± 114.66 ng/mL) showed no significant difference (p = 0.448). Notably, RTCA-measured functional and toxical TcdB concentration was significantly decreased when mixed with pooled CDC samples supernatant (p = 0.030). Conclusion: This study explored the novel application of the RTCA assay in effectively discerning clinical CDI from CDC cases.

Compound Danshen dripping pills prevent early diabetic retinopathy: roles of vascular protection and neuroprotection.

Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.

High CD204+ tumor-associated macrophage density predicts a poor prognosis in patients with clear cell renal cell carcinoma.

Purpose: Tumor-associated macrophages (TAMs) play a crucial role in solid tumors and display varying characteristics depending on the specific tumor microenvironment (TME). The study investigated the presence and characteristics of TAMs in renal clear cell carcinoma (ccRCC) and assessed their influence on patient prognosis. Methods: Immunohistochemistry (IHC) was used to identify CD204+ TAMs in a cohort of 72 patients with ccRCC. Kaplan-Meier survival analysis and log-rank test were used to evaluate the prognostic significance of CD204+ TAMs in each group. The TCGA-KIRC cohort was used to analyze the relationship between CD204 and immunity. The functions of CD204+ TAMs in the TCGA-KIRC cohort were analyzed through GO enrichment analysis. Immunofluorescence (IF) was conducted to confirm the positive effects of CD204 on regulatory T (Treg) cells and exhausted T (Tex) cells. Results: There was a negative relation between high infiltration of CD204+ TAMs and both overall survival (OS) and progression-free survival (PFS) in ccRCC. A positive correlation was found between high-infiltrating CD204+ TAMs and distant organ metastasis, as well as lymph node metastasis. In the TCGA-KIRC cohort, the group with high expression of CD204 exhibited significant up-regulation of 120 genes as well as enrichment in the negative regulation of immunity. CD204 high-expression group showed up-regulation of Treg cells and Tex cells. Conclusion: The presence of CD204+ TAMs in ccRCC is associated with a negative prognosis in patients. The high infiltration of CD204 promotes distant organ metastasis by aggerating Treg cells and Tex cells.

[Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells].

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 µg/L), moderate (10 µg/L), and high (100 µg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid ß-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid ß-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid ß-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.

The interplay between memory control and emotion regulation.

Memory control (MC) and emotion regulation (ER) are critical cognitive functions for adapting to life's challenges, drawing significant research attention. Accumulating evidence suggests these processes are interrelated, yet a comprehensive discussion of their interplay remains lacking. We introduce an integrative framework exploring the mutual influence between MC and ER, composed of two interrelated branches: first, MC aids in ER through the retrieval of positive memories, intentional forgetting of undesirable content, and the adaptive updating of memory stores. Second, ER impacts MC by upregulating positivity and downregulating negativity in memories. The framework spotlights the need to harness MC-ER interplay for future research. Potential directions include utilizing MC to amplify ER capabilities, training ER skills to refine MC performance, and modulating the cognitive and neural overlapping of both processes to improve both functions. Delving into the MC-ER nexus advances understanding of the intricate emotion-memory relationship and holds great promise for developing novel behavioral interventions.