Advanced gene therapy system for the treatment of solid tumour: A review.

In contrast to conventional therapies that require repeated dosing, gene therapy can treat diseases by correcting defective genes after a single transfection and achieving cascade amplification, and has been widely studied in clinical settings. However, nucleic acid drugs are prone to catabolism and inactivation. A variety of nucleic acid drug vectors have been developed to protect the target gene against nuclease degradation and increase the transformation efficiency and safety of gene therapy. In addition, gene therapy is often combined with chemotherapy, phototherapy, magnetic therapy, ultrasound, and other therapeutic modalities to improve the therapeutic effect. This review systematically introduces ribonucleic acid (RNA) interference technology, antisense oligonucleotides, and clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing. It also introduces the commonly used nucleic acid drug vectors, including viral vectors (adenovirus, retrovirus, etc.), organic vectors (lipids, polymers, etc.), and inorganic vectors (MOFs, carbon nanotubes, mesoporous silica, etc.). Then, we describe the combined gene therapy modalities and the pathways of action and report the recent applications in solid tumors of the combined gene therapy. Finally, the challenges of gene therapy in solid tumor treatment are introduced, and the prospect of application in this field is presented.

Patchy profile sign in RAPID software: a specific marker for intracranial atherosclerotic stenosis in acute ischemic stroke.

Purpose: Identifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism. Method: Patients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated. Results: A total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p < 0.001). Interobserver agreement for identifying PPS was excellent (κ = 0.944). The sensitivity, specificity, PPV, NPV, and accuracy of the PPS for predicting ICAS were 52.6, 93.8, 83.3, 76.9, and 78.4%, respectively. Conclusion: The PPS on RAPID software is an imaging marker with high specificity for ICAS. Larger sample sizes are imperative to validate the findings.

Anti-Xa Activity Test Is Needed but Is Not Enough for Monitoring Fondaparinux Therapy Among Critically Ill Patients.

CONTEXT.­: Fondaparinux monitoring is not required among noncritically ill patients due to a predictable dose-response effect. However, this is debatable among critically ill patients, because fondaparinux bioavailability can be influenced by complicated medical conditions. OBJECTIVE.­: To investigate fondaparinux monitoring among the critically ill. DESIGN.­: Retrospective analysis of patients admitted in intensive care unit from February 2021 to December 2021, who received prophylactic fondaparinux and had anti-Xa activity tests. RESULTS.­: Of 156 anti-Xa values, 86 (55.1%) were within 0.10-0.50 µg/mL (the recommended prophylactic range), 38 (24.4%) were less than 0.10 µg/mL, 32 (20.5%) were greater than 0.50 µg/mL, demonstrating an unpredictable dose-response effect. Among 70 patients, thrombotic tendency was controlled in 32 (45.7%), thrombosis progressed in 22 (31.4%), bleeding events occurred in 16 (22.9%). Patients with progressed thrombosis had 17 of 54 (31.5%) anti-Xa less than 0.10 µg/mL, even though this proportion was greater than that of patients with controlled thrombotic tendency (11 of 72, 15.3%), it was similar to that of patients with bleeding (10 of 30, 33.3%), indicating a weak practicability of anti-Xa for monitoring fondaparinux efficacy. Thrombin-antithrombin complex showed a gradual decline among patients with controlled thrombotic tendency, but a bounce-back effect among patients with progressed thrombosis. Thrombelastography R value above the upper reference value occurred more frequently among patients with bleeding (4 of 6, 66.7%) compared to patients without bleeding (4 of 22, 18.2%) (P = .01). CONCLUSIONS.­: The fondaparinux dose-response effect was unpredictable among the critically ill; anti-Xa activity combined with thrombin-antithrombin complex and thrombelastography can be helpful to guide a precise fondaparinux therapy in this population.

Ampholytic ion-exchange magnetic beads: a promising tool for selecting short fragments in circulating cell-free DNA analysis.

Objective: For liquid biopsy of cancer, the extraction of circulating cell-free DNA (cfDNA) from plasma is required. We evaluated the efficacy of use of magnetic submicron particles coated with abundant small zwitterions (MSP-ZEWBs) for extracting short fragments of cfDNA. Methods: We developed and optimized an MSP-ZEWB-based cfDNA extraction method using ampholytic ion-exchange materials and compared its results with those using a control kit. We measured the cfDNA concentration by quantitative polymerase-chain-reaction and using the Qubit method and analyzed cfDNA fragmentation patterns using a bioanalyzer. Results: The fragment size of cfDNA isolated from glycine hydrochloric acid at a pH of 2.2 exhibited a better alignment with the DNA marker. The highest DNA intensity was observed at the final concentration of 0.8% polyethylene glycol 8000. The intensity of cfDNA decreased significantly when isolated from plasma with DNA marker using MSP-ZEWBs with an adsorption buffer containing guanidine hydrochloride or isothiocyanoguanidine. All fragments were successfully extracted using MSP-ZEWBs from both plasma and phosphate-buffered saline. Notably, the intensity of short cfDNA fragments isolated using MSP-ZEWBs remained consistent for recovery of long DNA fragments. indicating a potential selective of small fragments. Conclusion: The extraction of plasma cfDNA with MSP-ZEWBs requires no protein denaturation, shows resistance to cells remaining in plasma, and demonstrates higher overall efficiency and better reproducibility than other extraction methods. Use of MSP-ZEWBs may greatly enhance liquid biopsy of cancers through the analysis of plasma cfDNA in clinical practice.

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality.

BACKGROUND: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. METHODS: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. RESULTS: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60-0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. CONCLUSION: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

Efficacy and safety of bismuth quadruple regimens containing minocycline and vonoprazan for eradication of Helicobacter pylori: Real-world evidence.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

Efficient Adsorbent Derived from Phytolith-Rich Ore for Removal of Tetracycline in Wastewater.

In recent decades, the tetracycline (TC) concentration in aquatic ecosystems has gradually increased, leading to water pollution problems. Various mineral adsorbents for the removal of tetracyclines have garnered considerable attention. However, efficient adsorbents suitable for use in a wide pH range environment have rarely been reported. Herein, a phytolith-rich adsorbent (PRADS) was prepared by a simple one-step alkali-activated pyrolysis treatment using phytolith as a raw material for effectively removing TC. PRADS, benefiting from its porous structure, which consists of acid- and alkali-resistant, fast-adsorbing macroporous silica and mesoporous carbon, is highly desirable for efficient TC removal from wastewater. The results indicate that PRADS exhibited excellent adsorption performance and stability for TC over a wide pH range of 2.0-12.0 under the coexistence of competing ions, which could be attributed to the fact that PRADS has a porous structure and contains abundant oxygen-containing functional groups and a large number of bonding sites. The adsorption mechanisms of PRADS for TC were mainly attributed to pore filling, hydrogen bonding, π-π electron-donor-acceptor, and electrostatic interactions. This work could offer a novel preparation strategy for the effective adsorption of pollutants by new functionalized phytolith adsorbents.

Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Right ventricular-pulmonary arterial coupling ratio derived from 3-dimensional echocardiography predicts outcomes in systemic lupus erythematosus-associated pulmonary arterial hypertension patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). METHODS: From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. RESULTS: During a median of 24 months (IQR 18-31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65-2.3) versus 1.30 (1.09-1.46) versus 0.64 (0.59-0.67), p < .001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = -0.621, p < .001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. CONCLUSIONS: The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention.

Investigating the Structure-property Relationships of Two Cd-based Hybrid Multifunctional Compounds with High Tc, Bright Fluorescence and Wide Band-gap.

Organic-inorganic hybrid multifunctional materials have shown significant application in lighting and sensor fields, owing to their prominent performance and diversity structures. Herein, we synthesized two multifunctional compounds: (propyl-quinuclidone)2 CdBr4 (1) and (F-butyl-quinuclidone)2 CdBr4 (2). By introducing light-emitting organic cation with flexible long chain, 1 and 2 exhibit excellent transition properties and bright blue-white fluorescence. Then, combine fluorescence lifetime and first-principal calculation, providing evidence for the electron transfer emission. Subsequently, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C-C to C-F) and halide framework (Cl to I) on the fluorescence properties. Results indicate that Cd⋅⋅⋅Cd distance and structural rigidity play an important role in fluorescence. Overall, our research provides valuable insight and example for chemical modifications enhance compound performance.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

A novel porous hydroxyapatite scaffold (pHAMG) enhances angiogenesis and osteogenesis around dental implants by regulating the immune microenvironment.

OBJECTIVE: The purpose was to evaluate whether a novel porous hydroxyapatite (HA) scaffold with a 25-30-µm groove structure (pHAMG) may improve bone osteogenesis, angiogenesis, and bone integration of titanium dental implants in animal models. METHODS: The pHAMG was prepared by chemical precipitation method and its elemental composition and crystal structure were evaluated. The ability of the scaffolds to induce ectopic osteogenesis and the ability of scaffolds combined with titanium dental implants to induce orthotopic peri-implant angiogenesis, osteogenesis, and osteointegration were tested after implantation into the femur muscle pocket in rats and the mandibular defects in beagle dogs, respectively. The elemental composition was evaluated by SEM-EDS; the expression of the relevant osteogenic/inflammation marker and the anti-/pro-inflammation markers was evaluated by immunostaining and immunofluorescence, respectively. RESULTS: In animal experiments with ectopic and peri-implant osteogenesis, pHAMG resulted in significantly larger neovascularization by hematoxylin-eosin staining, as well as deposition of collagen fibers by Masson staining than HA. Meanwhile, microgrooves in pHAMG upregulate more bone morphogenetic protein (BMP) 2 and interleukin-4 (IL-4) and -10 (IL-10) and downregulate more IL-1ß and tumor necrosis factor-α (TNF-α) than that in HA. The pHAMG showed greater expression of arginase (Arg)-1 and lower expression of inducible nitric oxide synthase (iNOS) than HA. CONCLUSION: The novel pHAMG can better repair bone defects in ectopic and orthotopic model. It also transfers macrophages to anti-inflammatory phenotypes, promoting angiogenic and osteogenesis in scaffolds, and bone integration in implants. CLINICAL RELEVANCE: The novel pHAMG induce greater osteogenesis and angiogenesis which could be utilized in the clinical treatment.

Extracellular shuttling miR-21 contributes to esophageal cancers and human umbilical vein endothelial cell communication in the tumor microenvironment and promotes tumor angiogenesis by targeting phosphatase and tensinhomolog.

BACKGROUND: Cell-cell communication by carcinoma-derived exosomes can influence the tumor microenvironment (TME) and regulate cancer progression. Based on the overexpression of microRNA-21-5p (miR-21) in plasma from patients diagnosed with esophageal squamous cell carcinoma (ESCC) and exosomes from ESCC cell lines identified earlier, this study aimed to explore the influence of exosomal miR-21 within the TME. METHOD: ScRNA-Seq and Bulk RNA-Seq were integrated to elucidate the communication between cancer and endothelial cells. The functionality and mechanisms by which exo-miR-21 derived from carcinoma regulate endothelial cell-mediated angiogenesis were assessed using a cocultivation model of EC9706 cells and recipient human umbilical vein endothelial cells (HUVECs), through blood vessel formation experiments, luciferase reporter assays, RT-qPCR, and western blot analysis. RESULT: A total of 3842 endothelial cells were extracted from the scRNA-seq data of ESCC samples and reclustered into five cell subtype. Cell-cell communication analysis revealed cancer cells presented a strong interaction with angiogenesis-like endothelial cells in secreted signaling. MiR-21 was unregulated in ESCC and the carcinoma-derived exo-miR-21 was significantly raised in HUVECs. The exo-miR-21 promoted the proliferation and migration of HUVECs while also enhancing, closed mesh count, and junction number in HUVECs. Mechanistically, dual-luciferase reporter assay revealed that PTEN was the target of miR-21. Meanwhile, p-Akt was significantly increased and suppressed by inhibition of miR-21 and PI3K inhibitor LY294002. CONCLUSION: Exo-miR-21-mediated communication between endothelial and cancer cells plays a pivotal role in promoting the angiogenesis of ESCC. Therefore, controlling exo-miR-21 could serve as a novel therapeutic strategy for ESCC by targeting angiogenesis.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

A Lightweight Recognition Method for Rice Growth Period Based on Improved YOLOv5s.

The identification of the growth and development period of rice is of great significance to achieve high-yield and high-quality rice. However, the acquisition of rice growth period information mainly relies on manual observation, which has problems such as low efficiency and strong subjectivity. In order to solve these problems, a lightweight recognition method is proposed to automatically identify the growth period of rice: Small-YOLOv5, which is based on improved YOLOv5s. Firstly, the new backbone feature extraction network MobileNetV3 was used to replace the YOLOv5s backbone network to reduce the model size and the number of model parameters, thus improving the detection speed of the model. Secondly, in the feature fusion stage of YOLOv5s, we introduced a more lightweight convolution method, GsConv, to replace the standard convolution. The computational cost of GsConv is about 60-70% of the standard convolution, but its contribution to the model learning ability is no less than that of the standard convolution. Based on GsConv, we built a lightweight neck network to reduce the complexity of the network model while maintaining accuracy. To verify the performance of Small-YOLOv5s, we tested it on a self-built dataset of rice growth period. The results show that compared with YOLOv5s (5.0) on the self-built dataset, the number of the model parameter was reduced by 82.4%, GFLOPS decreased by 85.9%, and the volume reduced by 86.0%. The mAP (0.5) value of the improved model was 98.7%, only 0.8% lower than that of the original YOLOv5s model. Compared with the mainstream lightweight model YOLOV5s- MobileNetV3-Small, the number of the model parameter was decreased by 10.0%, the volume reduced by 9.6%, and the mAP (0.5:0.95) improved by 5.0%-reaching 94.7%-and the recall rate improved by 1.5%-reaching 98.9%. Based on experimental comparisons, the effectiveness and superiority of the model have been verified.

Role of gender and age in features of Wilson's disease.

Background: Wilson's disease (WD) is a recessive genetic disorder characterized by copper metabolism dysfunction. It is difficult to obtain an accurate diagnosis due to its variable clinical presentation. This study aimed to describe the clinical characteristics and diagnostic particularities in a series of Chinese WD patients. Methods: The medical records of 371 patients with WD retrieved from January 2005 to December 2020 were retrospectively reviewed. Results: The incidence of WD has a male predominance in the adult population. However, the difference in sex distribution is not significant in the pediatric population. Females have an earlier symptom onset than males. The most common initial symptoms were neuropsychiatric manifestations both in the pediatric population (49.7%) and adult population (69.8%), and there was a male predominance (61.8%). Eighty-two percent of patients presented with more than two neurologic symptoms. Fifty-two (14%) patients presented with psychiatric symptoms. The most common WD phenotype was the neuropsychiatric form (48%). The age of onset occurred earlier in patients with the hepatic phenotype than in those with the neuropsychiatric phenotype. Moreover, there was a significant difference in sex distribution regarding phenotype. Females presented with a hepatic phenotype more often than males, and the neuropsychiatric phenotype occurred more frequently in males with an older onset age. Further study showed that the age at onset was a deciding factor for predicting the neuropsychiatric phenotype among the hepatic phenotype. However, sex did not correlate with the phenotype. Conclusion: Males seem to have a higher disease susceptibility, with symptom onset later than females. Males frequently present with a neuropsychiatric phenotype, while females present with a hepatic phenotype. Age at onset was a deciding factor for predicting the WD phenotype. Further studies focusing on the effect of estrogens on the pathology of WD are suggested.

2-Chloroethylamine·trifluoromethanesulfonate combined with 18-crown-6: a ferroelectric with excellent dielectric switching properties.

Ferroelectric materials are not only important electronic functional materials, but also considered as the most promising intelligent basic materials, because they show good application prospects. Therefore, it is an urgent task to develop and explore new ferroelectric material systems. In addition, the most important feature of crown ethers is their ability to complex with positive ions, which is extremely useful in synthesis. We report that [NH3C2H4Cl(18-crown-6)](CF3SO3) (1) has a phase transition temperature Tc = 255 K, and there is an obvious SHG switch below Tc. At the same time, the saturation polarization value Ps = 1.25 µC cm-2 is obtained from the hysteresis loop, which directly proves the ferroelectric nature of compound 1. It is noteworthy that the second harmonic response test of compound 1 shows a symmetric transition from a non-centrosymmetric to a centrosymmetric point group, that is a symmetry break from the paraelectric phase to the ferroelectric phase. This work is expected to promote the further exploration of organic crown ether ferroelectrics and provide a way to design and synthesize organic crown ether ferroelectrics.