Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping.

The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young's modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL-1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN/AKT signaling phosphorylation and neutrophil chemotaxis.

BACKGROUND: Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. METHODS: We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. RESULTS: We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. CONCLUSIONS: Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.

Intracranial Pressure Monitoring in Patients with Spontaneous Intracerebral Hemorrhage: A Systematic Review with Meta-Analysis.

OBJECTIVE: To describe the potential effects of Intracranial pressure monitoring on the outcome of patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This study is a systematic review with meta-analysis. Patients with spontaneous ICH treated with intracranial pressure monitoring were included. The primary outcome was mortality at 6 months and in-hospital mortality. The secondary outcome was poor neurological function outcome at 6 months. RESULTS: This analysis compares in-hospital and 6-month mortality rates between patients with intracranial pressure monitoring (ICPm) and those without (no ICPm). Although the ICPm group had a lower in-hospital mortality rate, it was not statistically significant (24.9% vs. 34.1%; OR 0.51, 95% CI 0.20 to 1.31, P = 0.16). Excluding patients with intraventricular hemorrhage revealed a significant reduction in in-hospital mortality for the ICPm group (23.5% vs. 43%; OR 0.39, 95% CI 0.29 to 0.53, P < 0.00001). For 6-month mortality, the ICPm group showed a significant reduction (32% vs. 39.6%; OR 0.76, 95% CI 0.61 to 0.94, P = 0.01), with the effect being more pronounced after excluding intraventricular hemorrhage patients (29.1% vs. 47.2%; OR 0.45, 95% CI 0.34 to 0.60, P < 0.0001). However, there were no statistically significant differences in 6-month functional outcomes between the groups. Increased ICP was associated with higher 3-month mortality (OR 1.12, 95% CI 1.07 to 1.18, P < 0.00001) and lower likelihood of good functional outcomes (OR 1.11, 95% CI 1.04 to 1.18, P < 0.00001). CONCLUSIONS: Elevated ICP is associated with increased mortality and poor prognosis in ICH patients. Although continuous intracranial pressure monitoring may reduce short-term mortality rates in specific subgroups of ICH patients, it does not improve neurological functional outcomes. While potential patient populations may benefit from ICP monitoring, more research is needed to screen suitable populations for ICP monitoring.

Use of carbon dioxide fractional laser in the management of lower limb ischemia in patients with diabetes: a case report : CO2 fractional laser in the treatment of diabetic foot.

Treatment of lower limb ischemia in patients with diabetes is challenging because of the location of the ulcers and the complexity of their pathogenesis. Carbon dioxide fractional laser (CO2FL) therapy in conjunction with tibial periosteum distraction could become a substitute for conventional methods. We herein describe a patient diagnosed with ischemic diabetic foot with a complex ulcer in the upper third of the tibia. Laser irradiation (Deep FX mode with 30 mJ of energy and 10% density) was applied to the entire region of skin below the knee after surface anesthesia, and this treatment was performed twice a week until the ulcer healed. Computed tomography angiography showed successful establishment of a blood supply to the back of the right foot after treatment. Skin grafting was successfully performed, with only a few wounds remaining on the foot 8 months after treatment. The pain score was significantly decreased at the last follow-up. No complications occurred. This case report provides guidance for the performance of CO2FL, a fast, easy, accurate treatment in patients with diabetes. CO2FL can target lower limb arterial occlusive disease accompanied by refractory ulcers, addressing the underlying vascular occlusion and dysfunction as well as promoting microcirculation and wound healing.

Performance of the neural network-based prediction model in closed-loop adaptive optics.

Adaptive optics (AO) technology is an effective means to compensate for atmospheric turbulence, but the inherent delay error of an AO system will cause the compensation phase of the deformable mirror (DM) to lag behind the actual distortion, which limits the correction performance of the AO technology. Therefore, the feed-forward prediction of atmospheric turbulence has important research value and application significance to offset the inherent time delay and improve the correction bandwidth of the AO system. However, most prediction algorithms are limited to an open-loop system, and the deployment and the application in the actual AO system are rarely reported, so its correction performance improvement has not been verified in practice. We report, to our knowledge, the first successful test of a deep learning-based spatiotemporal prediction model in an actual 3 km laser atmospheric transport AO system and compare it with the traditional closed-loop control methods, demonstrating that the AO system with the prediction model has higher correction performance.

Atomic Ru-Pt dual sites boost the mass activity and cycle life of alkaline hydrogen evolution.

The development of highly efficient and ultrastable electrocatalysts for hydrogen generation from water/real seawater faces huge challenges. Herein, porous carbon-supported amorphous RuPt nanoclusters (Ru5.67Pt/PC) achieve mass activities of 42.28/10.93 A mgPt-1 and ultralong cycling stability in alkaline water/seawater because of the unique cluster structure and atomic Ru-Pt dual sites.

[Advances in clinical management of neonatal sepsis]. / 新生儿败血症的临床管理进展.

Neonatal sepsis, as a significant cause of various complications and adverse outcomes in neonates, remains a serious health burden both domestically and internationally. Strategies such as antibiotic prophylaxis during delivery, the utilization of early-onset sepsis risk calculators, and quality improvement initiatives in neonatal wards are beneficial in alleviating the disease burden of neonatal sepsis. This paper provides a review of the epidemiology, risk factors, and recent advances in clinical management of neonatal sepsis.

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.

A delayed 400 GeV photon from GRB 221009A and implication on the intergalactic magnetic field.

Large High Altitude Air Shower Observatory has detected 0.2 - 13 TeV emission of GRB 221009A within 2000 s since the trigger. Here we report the detection of a 400 GeV photon, without accompanying prominent low-energy emission, by Fermi Large Area Telescope in this direction with a 0.4 days' delay. Given an intergalactic magnetic field strength of about 4 × 10-17 G, which is comparable to limits from TeV blazars, the delayed 400 GeV photon can be explained as the cascade emission of about 10 TeV gamma rays. We estimate the probabilities of the cascade emission that can result in one detectable photon beyond 100 GeV by Fermi Large Area Telescope within 0.3 - 1 days is about 2% whereas it is about 20.5% within 0.3 - 250 days. Our results show that Synchrotron Self-Compton explanation is less favored with probabilities lower by a factor of about 3 - 30 than the cascade scenario.

Crystalline-Amorphous Heterophase PdMoCrW Tetrametallene: Highly Efficient Oxygen Reduction Electrocatalysts for a Long-Term Zn-Air Battery.

Metallenes have received sustained attention owing to their unique microstructure characteristics and compelling catalytic applications, but the synthesis of multielement crystalline-amorphous metallenes remains a formidable challenge. Herein, we report a one-step wet chemical reduction method to synthesize composition-tunable crystalline-amorphous heterophase PdMoCrW tetrametallene. As-synthesized PdMoCrW tetrametallene is composed of approximately six to seven atomic layers and has flexible crimpiness, a crystalline-amorphous heterophase structure, and high-valence metal species. Time-dependent experiments show that PdMoCrW tetrametallene follows a three-step growth mechanism that includes nucleation, lateral growth, and atom diffusion, respectively. The novel ultrathin structure, optimized Pd electronic structure, and hydrophilic surface together greatly promote the activity and stability of PdMoCrW tetrametallene in the alkaline oxygen reduction reaction. Pd75.9Mo9.4Cr8.9W5.8/C exhibits excellent mass and specific activities of 2.81 A mgPd-1 and 4.05 mA cm-2, which are 20.07/14.46 and 23.42/16.20 times higher than those of commercial Pt/C and Pd/C, respectively. Furthermore, a Zn-air battery assembled using Pd75.9Mo9.4Cr8.9W5.8/C as a cathode catalyst achieves a peak power density of 156 mW cm-2 and an ultralong durability of 329 h. This study reports an effective strategy for constructing crystalline-amorphous quaternary metallenes to advance non-Pt electrocatalysts toward oxygen reduction reaction (ORR) performance and for a Zn-air battery.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study.

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Isavuconazole Induces Neurodevelopment Defects and Motor Behaviour Impairment in Zebrafish Larvae.

Isavuconazole is a broad-spectrum antifungal drug used for the treatment of serious infections caused by invasive aspergillosis and mucormycosis in adults. With the continuous use of this drug, its safety and environmental impact have received increasing attention. However, information on the adverse effects of the drug is very limited. Fish is a particularly important model for assessing environmental risks. In this study, the aquatic vertebrate zebrafish was used as a model to study the toxic effects and mechanisms of isavuconazole. We exposed zebrafish embryos to 0.25, 0.5, and 1 mg/L of isavuconazole 6 h after fertilization. The results showed that at 72 hpf, isavuconazole exposure reduced heart rate, body length, and survival of zebrafish embryos compared to controls. Secondly, when isavuconazole reached a certain dose level (0.25 mg/L), it caused morphological changes in the Tg(elavl3:eGFP) transgenic fish line, with the head shrunk, the body bent, the fluorescence intensity becoming weaker, the abnormal motor behaviour, etc. At the same time, exposure of zebrafish embryos to isavuconazole downregulated acetylcholinesterase (AchE) and adenosine triphosphate (ATPase) activities but upregulated oxidative stress, thereby disrupting neural development and gene expression of neurotransmitter pathways. In addition, astaxanthin partially rescued the neurodevelopmental defects of zebrafish embryos by downregulating oxidative stress. Thus, our study suggests that isavuconazole exposure may induce neurodevelopment defects and behavioural disturbances in larval zebrafish.

[Correlation between combined deflection angle classification adduction typing and complications after internal fixation of adduction femoral neck fracture].

Objective: To analyze the correlation between postoperative complications and combined deflection angle classification adduction type (CDAC-ADT) of femoral neck fractures after cannulated screw internal fixation. Methods: The clinical data of 121 patients with CDAC-ADT femoral neck fracture admitted between January 2018 and December 2021 and met the selected criteria were retrospectively analyzed. There were 69 males and 52 females, the age ranged from 19 to 79 years (mean, 48.1 years). The causes of injury included 52 cases of traffic accident, 24 cases of falling from height, and 45 cases of fall. The time from injury to operation ranged from 2 to 12 days, with an average of 6.0 days. Among them, there were 18 cases of CDAC-ADT type Ⅰ, 46 cases of type Ⅱ, and 57 cases of type Ⅲ; 6 cases of Garden type Ⅱ, 103 cases of type Ⅲ, and 12 cases of type Ⅳ; and according to the location of the fracture line, there were 26 cases of subcapitate type, 88 cases of transcervical type, and 7 cases of basal type. All patients were treated with cannulated screw internal fixation. The occurrence of complications (including internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head) was recorded, and the correlation between complications and CDAC-ADT typing, Garden typing, and fracture line location were analyzed. Results: The patients were followed up 8-44 months, with a mean of 24.9 months. There were 10 cases of internal fixation failure, 7 cases of fracture nonunion, and 30 cases of osteonecrosis of the femoral head after operation. Correlation analysis showed that patients' CDAC-ADT typing was significantly correlated with the overall incidence of complication and the incidence of internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head ( P<0.05), and the Pearson coefficient of contingency were 0.435, 0.251, 0.254, and 0.241, respectively. Garden typing did not correlate with the overall incidence of complication and the incidence of internal fixation failure and fracture nonunion ( P>0.05), but correlated with the incidence of osteonecrosis of the femoral head ( P<0.05), and the Pearson coefficient of contingency was 0.251. Fracture line position typing had no correlation with the overall incidence of complication and the incidence of internal fixation failure, fracture nonunion, and osteonecrosis of the femoral head ( P>0.05). Conclusion: CDAC-ADT typing has obvious correlation with postoperative complications of femoral neck fracture and can be used to predict complications of femoral neck fracture.

Half-decomposition of salt-bearing dolomite.

Half-calcined dolomites (HCDs) have been widely used in environmental remediation, medicine, and construction. However, advanced calcination technologies are required to modify their microstructure and thus improve their working performance. Herein, we investigated the effects of a variety of inorganic salts on the decomposition of dolomite based on thermogravimetric, compositional, and morphological analysis. The thermogravimetric data showed that certain salts significantly lowered the half-decomposition temperature of dolomite, which included LiCl, CaCl2, MgCl2, AlCl3, LiNO3, KNO3, K2CO3, Li2CO3, Li2SO4, Na3PO4, and K3PO4. Compositional analysis demonstrated that only half-decomposition occurred when salt-bearing dolomite was calcined at a temperature of 723-923 K, leading to the formation of CaO-free HCDs composed of periclase and Mg-calcite having a Mg level of 2.0-10.5 mol%. Morphological analysis showed that porous HCDs were feasibly obtained by calcining salt-bearing dolomite at 723-923 K. MgO coarsening occurred at a temperature above 873 K, but it could be avoided by controlling the calcination time. The mechanism of salts may be related to the heterovalent doping effect, which may lead to an increase in the concentration of vacancies in the dolomite lattice.

Polarization smoothing based on full Poincaré beams modulated by stress-engineered optics.

In laser-driven inertial confinement fusion (ICF) facilities, nonuniform laser irradiation can cause significant challenges, such as hydrodynamics instability and laser plasma instability, which hinder the success of fusion. This article presents a new idea for improving the uniformity of far-field laser irradiation through a method of single-beam polarization smoothing. The method involves modulating full Poincaré beams using stress-engineered optics made from fused silica. We designed a stress birefringence system and conducted opto-mechanical modeling and analysis on it. The article elaborates on the mechanism and principles of generating large-aperture full Poincaré beams by stress birefringence, as well as the mechanism of polarization smoothing by full Poincaré beams. Near-field polarization measurements were conducted to verify these mechanisms, and the effectiveness of this method in improving the uniformity of laser irradiation in the target area was evaluated through far-field optical tests.

[Design and application of a drainage tube dredging umbrella and anti-retrograde infection kit].

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Mesoporous Mo-doped PtBi intermetallic metallene superstructures to enable the complete electrooxidation of ethylene glycol.

Metallenes, intermetallic compounds, and porous nanocrystals are the three types of most promising advanced nanomaterials for practical fuel cell devices, but how to integrate the three structural features into a single nanocrystal remains a huge challenge. Herein, we report an efficient one-step method to construct freestanding mesoporous Mo-doped PtBi intermetallic metallene superstructures (denoted M-PtBiMo IMSs) as highly active and stable ethylene glycol oxidation reaction (EGOR) catalysts. The materials retained their catalytic performance, even in complex direct ethylene glycol fuel cells (DEGFCs). The M-PtBiMo IMSs showed EGOR mass and specific activities of 24.0 A mgPt-1 and 61.1 mA cm-2, respectively, which were both dramatically higher than those of benchmark Pt black and Pt/C. In situ infrared spectra showed that ethylene glycol underwent complete oxidation via a 10-electron CO-free pathway over the M-PtBiMo IMSs. Impressively, M-PtBiMo IMSs demonstrated a much higher power density (173.6 mW cm-2) and stability than Pt/C in DEGFCs. Density functional theory calculations revealed that oxophilic Mo species promoted the EGOR kinetics. This work provides new possibilities for designing advanced Pt-based nanomaterials to improve DEGFC performance.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.