Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

Pre-Operative Immunonutrition Enhances Postoperative Outcomes and Elevates Tumor-Infiltrating Lymphocyte Counts in Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery. METHODS: We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors. RESULTS: A total of 16 studies were finally included. Preoperative immunonutrition could reduce the postoperative infection rate (risk ratio (RR) = 0.56, 95% confidence interval (CI): 0.36, 0.88; p = .01), and wound infection rate (RR = 0.44, 95% CI: 0.27, 0.70; p < .001) in patients with colorectal cancer. For length of stay (mean difference (MD) = -1.10, 95% CI: -2.70, 0.49; p = .17), it was similar between groups. Meanwhile, patients in the pre-operation immune nutrition group also had significantly increased infiltrative lymphocytes CD16+ (MD = 0.04, 95% CI: 0.02, 0.06; p < .001), and CD56+ (MD = 0.05, 95% CI: 0.03, 0.06; p < .001) cells in the tumor tissues, compared to the control group. CONCLUSION: Immunonutrition intervention has the potential to reduce postoperative infectious complications and improve tumor infiltrative lymphocytes in patients with colorectal cancer undergoing surgery.

Rapid low-temperature densification of Ag2Se bulk material: mass transfer through the dissociative adsorption reaction of Ag protrusions and Se saturated vapor.

In materials science, the impact of density on a material's capabilities is profound. Conventional sintering requires high temperatures and is energy-demanding, propelling the pursuit of less intensive, low-temperature densification methods. Electric field-assisted sintering has recently gained attention for its simplicity and effectiveness, offering a new frontier in low-temperature densification. In this study, dense bulk materials were produced by subjecting monophasic Ag2Se powders to electric field-assisted sintering, where a direct current with an average value of 4 A was applied, achieving a peak temperature of 344 K. The novel low-temperature densification mechanism unfolds thus: nanoscale silver protrusions, stimulated by electrical current, engage in a dissociative adsorption reaction with the ambient saturated selenium vapor. This process swiftly engenders the formation of fresh silver selenide (Ag2Se) compounds, initiating nucleation and subsequent growth. Consecutively, these compounds seamlessly occupy and expand, perpetually bridging the interstices amidst the powders. In a scant 8 s, the density swiftly surpassed 99%, yielding a bulk material that exhibited aZTvalue of 1.07 at 390 K. This investigation not only attains an unparalleled density at low temperatures but also charts a pioneering course for material densification in such conditions.

Telemedicine in Improving Glycemic Control Among Children and Adolescents With Type 1 Diabetes Mellitus: Systematic Review and Meta-Analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease among children and adolescents. Telemedicine has been widely used in the field of chronic disease management and can benefit patients with T1DM. However, existing studies lack high-level evidence related to the effectiveness of telemedicine for glycemic control in children and adolescents with T1DM. OBJECTIVE: This study aims to systematically review the evidence on the effectiveness of telemedicine interventions compared with usual care on glycemic control among children and adolescents with T1DM. METHODS: In this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science (all databases), and CINAHL Complete from database inception to May 2023. We included randomized controlled trials (RCTs) that evaluated the effectiveness of a telemedicine intervention on glycemic control in children and adolescents with T1DM. In total, 2 independent reviewers performed the study selection and data extraction. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Our primary outcome was glycated hemoglobin (HbA1c) levels. Secondary outcomes were quality of life, self-monitoring of blood glucose, the incidence of hypoglycemia, and cost-effectiveness. A random-effects model was used for this meta-analysis. RESULTS: Overall, 20 RCTs (1704 participants from 12 countries) were included in the meta-analysis. Only 5% (1/20) of the studies were at high risk of bias. Compared to usual care, telemedicine was found to reduce HbA1c levels by 0.22 (95% CI -0.33 to -0.10; P<.001; I2=35%). There was an improvement in self-monitoring of blood glucose (mean difference [MD] 0.54, 95% CI -0.72 to 1.80; P=.40; I2=67.8%) and the incidence of hypoglycemia (MD -0.15, 95% CI -0.57 to 0.27; P=.49; I2=70.7%), although this was not statistically significant. Moreover, telemedicine had no convincing effect on the Diabetes Quality of Life for Youth score (impact of diabetes: P=.59; worries about diabetes: P=.71; satisfaction with diabetes: P=.68), but there was a statistically significant improvement in non-youth-specific quality of life (MD -0.24, 95% CI -0.45 to -0.02; P=.04; I2=0%). Subgroup analyses revealed that the effect of telemedicine on HbA1c levels appeared to be greater in studies involving children (MD -0.41, 95% CI -0.62 to -0.20; P<.001), studies that lasted <6 months (MD -0.32, 95% CI -0.48 to -0.17; P<.001), studies where providers used smartphone apps to communicate with patients (MD -0.37, 95% CI -0.53 to -0.21; P<.001), and studies with medication dose adjustment (MD -0.25, 95% CI -0.37 to -0.12; P<.001). CONCLUSIONS: Telemedicine can reduce HbA1c levels and improve quality of life in children and adolescents with T1DM. Telemedicine should be regarded as a useful supplement to usual care to control HbA1c levels and a potentially cost-effective mode. Meanwhile, researchers should develop higher-quality RCTs using large samples that focus on hard clinical outcomes, cost-effectiveness, and quality of life.

Switching indoor fuels and the incidence of physical-psychological-cognitive multimorbidity: A prospective cohort study.

BACKGROUND: In developing countries, including China, solid-fuel-based heating and cooking is common. For older people, the multimorbidity prevalence is exceptionally high. Nevertheless, studies on the associations of indoor solid fuels use, especially switching fuels types, on multimorbidity in middle-aged and older people is scarce. METHODS: Data from five waves of the China Health and Retirement Longitudinal Study were used in this study. Indoor fuels were classified as solid or clean fuels. Physical-psychological-cognitive multimorbidity (PPC-multimorbidity) was defined as the simultaneous presence of three disease types (physical illness, psychological disorders, cognitive impairment). Using Cox proportional risk models, hazard ratios (HRs) and 95 % confidence intervals (95 % CI) were calculated to investigate the associations of heating- and cooking-related baseline indoor fuels and switching indoor fuels with PPC-multimorbidity incidence. RESULTS: In the heating (n=3121, mean age=56.55 years, male proportion=54.25 %) and cooking (n=3574, mean age=56.67 years, male proportion=52.94 %) analyses, 75.07 % and 45.64 % of the participants used solid fuels at baseline, and 564 (18.07 %) and 613 (17.15 %) PPC-multimorbidity cases were diagnosed during follow-up, respectively. Participants with baseline heating- and cooking-based solid fuels use had greater PPC-multimorbidity incidences [HRs (95 % CIs): 1.23 (0.98, 1.55) and 1.44 (1.21, 1.73)], respectively. Additionally, combined baseline heating- and cooking-based solid fuels use was associated with even greater PPC-multimorbidity incidence [HR (95 % CI): 1.55 (1.18, 2.04)]. Persistent solid fuels use obviously increased the PPC-multimorbidity incidence [HRs (95 % CIs): 2.43 (1.67, 3.55) for heating and 2.63 (2.03, 3.40) for cooking]. Moreover, switching from solid to clean fuels was associated with a significantly decreased PPC-multimorbidity incidence [HRs (95 % CIs): 0.27 (0.20, 0.35) for heating and 0.36 (0.28, 0.46) for cooking]. CONCLUSIONS: Long-term solid-fuels use is associated with an increased PPC-multimorbidity incidence, and switching to cleaner fuels is associated with a decreased PPC-multimorbidity incidence in adults aged ≥45 years.

The regulatory mechanism of rapid lignification for timely anther dehiscence.

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.

Prediction models for skin tears in the elderly: A systematic review and meta-analysis.

BACKGROUND: The prevalence of risk prediction models for skin tears in the elderly is growing; however, there is still debate regarding the usefulness and suitability of these models for clinical use and additional study. OBJECTIVE: The purpose of this work is to perform a systematic review and meta-analysis of published research on skin tear risk prediction models in the elderly. METHODS: We conducted a comprehensive search of various databases, including Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, PubMed, Web of Science, MEDLINE, Scopus, The Cochrane Library, Wanfang Database, China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI), from the beginning until November 27, 2023. Data extraction from the chosen studies encompassed various elements, such as study design, sample size, outcome definition, data source, predictors, model development, and performance. The assessment of bias and applicability was conducted using the Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist. The Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist was utilized to assess the transparency in reporting the prediction models-a meta-analysis of the most common predictors to assess predictor reliability. In addition, a narrative synthesis was carried out to provide an overview of the qualities, bias risk, and effectiveness of the current models. The reporting procedures of this meta-analysis conformed to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement. RESULTS: Out of the initially retrieved 1499 studies, this review included eight prediction models from eight selected studies. All the studies employed logistic regression to develop prediction models for skin tears. The prevalence of skin tears in the elderly varied from 3.0% to 33.3%. Senile purpura and a history of previous skin tears were the most commonly utilized predictors. The reported values for the area under the curve (AUC) ranged from 0.765 to 0.854. All the studies exhibited a high risk of bias, primarily due to inadequate reporting in the outcome and analysis domains. Furthermore, serious questions concerning their applicability were highlighted by four studies. CONCLUSION: Based on the PROBAST checklist, the current models for predicting skin tears in the elderly showed a high risk of bias. The development of new prediction models with bigger sample sizes, appropriate study designs, and external validation from multiple sources ought to be the primary focus of future research. PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution to this systematic review. REGISTRATION: PROSPERO registration number: CRD42023494387.

Spatially Resolved Metabolomics Combined with the 3D Tumor-Immune Cell Coculture Spheroid Highlights Metabolic Alterations during Antitumor Immune Response.

The metabolic cross-talk between tumor and immune cells plays key roles in immune cell function and immune checkpoint blockade therapy. However, the characterization of tumor immunometabolism and its spatiotemporal alterations during immune response in a complex tumor microenvironment is challenging. Here, a 3D tumor-immune cell coculture spheroid model was developed to mimic tumor-immune interactions, combined with mass spectrometry imaging-based spatially resolved metabolomics to visualize tumor immunometabolic alterations during immune response. The inhibition of T cells was simulated by coculturing breast tumor spheroids with Jurkat T cells, and the reactivation of T cells can be monitored through diminishing cancer PD-L1 expressions by berberine. This system enables simultaneously screening and imaging discriminatory metabolites that are altered during T cell-mediated antitumor immune response and characterizing the distributions of berberine and its metabolites in tumor spheroids. We discovered that the transport and catabolism of glutamine were significantly reprogrammed during the antitumor immune response at both metabolite and enzyme levels, corresponding to its indispensable roles in energy metabolism and building new biomass. The combination of spatially resolved metabolomics with the 3D tumor-immune cell coculture spheroid visually reveals metabolic interactions between tumor and immune cells and possibly helps decipher the role of immunometabolic alterations in tumor immunotherapy.

Experimental free-space continuous-variable quantum key distribution with thermal source.

Passive-state-preparation (PSP) continuous-variable quantum key distribution (CVQKD) protocol explores the intrinsic field fluctuations of a thermal source. Compared with traditional Gaussian-modulated coherent-state CVQKD, it does not need active modulations and has promising applications in chip integration and portable free-space quantum key distribution. In this Letter, we propose and experimentally realize a PSP CVQKD scheme with transmitted local oscillator (LO) through fluctuating transmittance free-space channel using an off-the-shelf amplified spontaneous emission source for the first time. By proposing thermal-state polarization multiplexing transmitted LO, synchronized channel transmittance monitoring and fine-grained phase compensation techniques, secure keys within -15 dB transmittance of simulated free-space channel with turbulence are generated, with a final average secure key rate of 1.015 Mbps asymptotically. Equivalent atmospheric turbulence model analysis shows that the free-space PSP CVQKD scheme provides a promising outlook for high-speed and chip-based CVQKD for kilometer-level atmospheric channel networks.

Study of the biological characteristics of human umbilical cord mesenchymal stem cells after long-time cryopreservation.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have considerable potential in cell therapy. Cryopreservation represents the gold standard in cell storage, but its effect on hUC-MSCs is still not well understood. The aim of this study was to investigate the effect of one year of cryopreservation and thawing on the biological characteristics of hUC-MSCs from the same donors. Fresh hUC-MSCs were cryopreserved in commercial freezing medium (serum-free CellBanker 2) at passage 2. After one year of cryopreservation, the hUC-MSCs were thawed and subcultured to passage 4. The comparison was performed in terms of followings: cell count, viability, morphology, proliferation capacity, differentiation potential and chromosomal stability. The total cell count and viability of hUC-MSCs before and after one year of cryopreservation were 1 × 107 and 96.34% and 0.943 × 107 and 93.81%, respectively. Cryopreserved and fresh hUC-MSCs displayed a similar cell doubling times, expressed the markers CD73, CD90, CD105 and were negative for the markers CD34, CD45, and HLA-DR. Karyotypes were found to be normal after one year of cryopreservation. The trilineage differentiation properties were maintained after cryopreservation. However, when compared to freshly isolated hUC-MSCs from the same donor, cryopreserved hUC-MSCs exhibited decreased expression of osteogenesis- and chondrogenesis-related genes including Runx2, Sox9, and Col1a1, and increased expression of adipogenesis-related genes. These results demonstrated that cryopreservation did not affect cell morphology, surface marker expression, cell viability, proliferative capacity, or chromosomal stability. However, the osteogenic and chondrogenic differentiation capacities of cryopreserved hUC-MSCs were slightly reduced compared with those of fresh cells from the same donor.

Intravitreal Injection of Human Retinal Progenitor Cells for Treatment of Retinal Degeneration.

BACKGROUND Retinal degeneration causes irreversible blindness. Human retinal progenitor cells (hRPCs) have the potential to treat retinal diseases. The vitreous cavity is a relatively immune-privileged site that is suitable for stem cell transplantation in the treatment of retinal diseases. This study aimed to evaluate the therapeutic efficacy and safety of intravitreal injection of hRPCs in retinal degeneration therapy. MATERIAL AND METHODS hRPCs were primary-cultured and injected into the vitreous cavity of RCS rats. To determine whether hRPCs formed teratomas in immune-deficient mice, hRPCs at different passages were transplanted into BALB/c-nu mice. The visual function was detected by electroretinography recording. Changes in the outer nuclear layer (ONL) were analyzed by histological testing and cell counting. The protective mechanism was further assessed by cytokine antibody array. RESULTS Intravitreal transplantation of hRPCs maintained retinal function and preserved retinal morphology. Importantly, grafted cells in the vitreous cavity were well tolerated, with no adverse effects. Teratoma was not formed in BALB/c-nu mice after hRPCs transplantation. The number of hRPCs-injected eyes and thickness of ONL in the hRPCs-treated group were higher than those in the untreated group and HBSS injection group. The cytokine antibody array revealed that hRPCs expressed GDF-15, PDGF-AA, EGF, and NT-4. CONCLUSIONS Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease.

Synergistic Effect of Permanganate and in Situ Synthesized Hydrated Manganese Oxide for Removing Antibiotic Resistance Genes from Wastewater Treatment Plant Effluent.

An increasing amount of attention has been given to antimicrobial resistance in the environment because of its substantial threat to human health. The effluent from municipal wastewater treatment plants has been regarded as one of the important sources for the spread of antibiotic resistance genes (ARGs). However, conventional disinfection techniques fail to effectively remove ARGs from effluents. In this work, in situ synthesized hydrated manganese oxide (HMO) coupled with permanganate was applied for the first time in ARG removal from the effluent of wastewater treatment plants. The results show that five ARGs (sulI, sulII, tetQ, tetO, and tetW) as well as the intI1 and 16S rRNA genes had removal efficiencies of 2.46-4.23 logs, which were significantly higher than those obtained by using these reagents individually. This implied that there was a synergistic effect between permanganate and HMO toward the removal of ARGs. Moreover, the contributions of HMO coagulation and permanganate oxidation to ARG removal were semiquantitatively studied, which demonstrated that destruction of the microbial cells by oxidation and removal of the extracellular ARGs released by coagulation were the two main processes in this system. The results of this study provide an alternative method for ARG removal from the effluent of wastewater treatment plants with high efficiencies to control the spreading of ARGs.

Gastric and cardiac inflammatory myofibroblastic tumor: an extremely rare case.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient's stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun's gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review. CONCLUSIONS: As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.

TROP2 promotes the proliferation of triple-negative breast cancer cells via calcium ion-dependent ER stress signaling pathway.

OBJECTIVE: To explore the molecular mechanisms of tumor-associated calcium signal transduction factor 2 (TROP2) affecting the occurrence and development of triple-negative breast cancer (TNBC). METHODS: The TCGA database, immunohistochemical staining, and qRT-PCR were used to analyze the expression of TROP2 in TNBC tissues and cells. The protein expressions of TROP2 and inositol 1,4,5-trisphosphate receptor (IP3R) after TROP2 knockdown were detected by western blot (WB). Cell proliferation was detected by CCK8 and colony formation assay, Annexin V-APC/PI flow cytometry was used to detect apoptosis, and intracellular calcium ion (Ca2+) was detected by flow cytometry with Fura 2-AM fluorescent probe. Finally, the morphological changes of the endoplasmic reticulum (ER) were observed by transmission electron microscopy, and the expression of ER stress (ERS)-related proteins was detected by WB and immunofluorescence staining. RESULTS: TROP2 was up-regulated in TNBC tumor tissues and cells. Silencing TROP2 decreased the proliferation rate and clone formation number, and increased the apoptosis rate and the Ca2+ level in TNBC cells. These phenomena were reversed after the addition of 2-APB. In addition, after TROP2 knockdown, the expressions of IP3R and ERS-related proteins were up-regulated, the ER was cystic dilated, and ERS was activated. And the addition of 2-APB significantly inhibited the activation of ERS induced by TROP2 knockdown. CONCLUSION: TROP2 regulated the proliferation and apoptosis of TNBC cells through a Ca2+-dependent ERS signaling pathway.

Advancing NSCLC pathological subtype prediction with interpretable machine learning: a comprehensive radiomics-based approach.

Objective: This research aims to develop and assess the performance of interpretable machine learning models for diagnosing three histological subtypes of non-small cell lung cancer (NSCLC) utilizing CT imaging data. Methods: A retrospective cohort of 317 patients diagnosed with NSCLC was included in the study. These individuals were randomly segregated into two groups: a training set comprising 222 patients and a validation set with 95 patients, adhering to a 7:3 ratio. A comprehensive extraction yielded 1,834 radiomic features. For feature selection, statistical methodologies such as the Mann-Whitney U test, Spearman's rank correlation, and one-way logistic regression were employed. To address data imbalance, the Synthetic Minority Over-sampling Technique (SMOTE) was utilized. The study designed three distinct models to predict adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Six different classifiers, namely Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, eXtreme Gradient Boosting (XGB), and LightGBM, were deployed for model training. Model performance was gauged through accuracy metrics and the area under the receiver operating characteristic (ROC) curves (AUC). To interpret the diagnostic process, the Shapley Additive Explanations (SHAP) approach was applied. Results: For the ADC, SCC, and LCC groups, 9, 12, and 8 key radiomic features were selected, respectively. In terms of model performance, the XGB model demonstrated superior performance in predicting SCC and LCC, with AUC values of 0.789 and 0.848, respectively. For ADC prediction, the Random Forest model excelled, showcasing an AUC of 0.748. Conclusion: The constructed machine learning models, leveraging CT imaging, exhibited robust predictive capabilities for SCC, LCC, and ADC subtypes of NSCLC. These interpretable models serve as substantial support for clinical decision-making processes.

TROP2 regulates cisplatin sensitivity of triple-negative breast cancer cells by regulating endoplasmic reticulum stress.

Triple-negative breast cancer (TNBC) is a kind of breast cancer with a high metastasis rate and poor prognosis. As a transmembrane glycoprotein, tumor-associated calcium signal transducer 2 (TROP2) plays a certain role in the cancers. This study aimed to explore the potential mechanism of TROP2 affecting cisplatin (CDDP) resistance in TNBC from endoplasmic reticulum stress (ERS). MDA-MB-231 and CDDP-resistant cell lines MDA-MB-231/CDDP were used in this study, and the expression of TROP2 was detected by western blotting. After transfecting with the interference sequence of siRNA targeting TROP2, cell proliferation and apoptosis were detected by the cell counting kit-8, colony formation, and flow cytometry, and the expression of ERS-marker proteins was detected by western blotting. Furthermore, the effects of ERS in TROP2 on drug resistance of TNBC cells were explored by using ERS inhibitor 4-phenylbutyric acid (4-PBA). Results found that TROP2 expression in MDA-MB-231/CDDP was significantly upregulated compared with MDA-MB-231. The expression of TROP2 in MDA-MB-231/CDDP was significantly decreased after transfection with siRNA-TROP2, and the proliferation of MDA-MB-231 and MDA-MB-231/CDDP cells was significantly decreased after further induction with CDDP. TROP2 significantly affected TNBC cell cloning, apoptosis, and the expression of ERS-related marker proteins, while 4-PBA reversed the promoting effects of siRNA-TROP2 on apoptosis and ERS, as well as the inhibitory effects on cell proliferation, suggesting that TROP2 affected the resistance of TNBC cells to CDDP through ERS. In conclusion, TROP2 inhibited apoptosis of TNBC cells, improved the cell cloning ability, and regulated the sensitivity of TNBC cells to CDDP through ERS.

Network evolution of core symptoms after lung cancer thoracoscopic surgery:A dynamic network analysis.

OBJECTIVES: To investigate relationships between various symptoms occurring 1-2 and 5-6 days following days after thoracoscopic surgery, to identify core symptoms, and to monitor changes in core symptoms over time following lung cancer thoracoscopic surgery. METHODS: We evaluated symptoms using the Anderson Symptom Scale (Chinese version) and the Lung Cancer-Specific Symptoms Template in 214 lung cancer patients hospitalized in the Department of Thoracic Surgery of a provincial hospital in Jiangsu Province from March 2023 to September 2023. Data was collected at 1-2 days and 5-6 days postoperatively. Symptom networks were constructed for each time point, and centrality indicators were analyzed to identify core symptoms while controlling for influencing factors. RESULTS: According to the network analysis, fatigue (rs = 26.00、rc = 0.05、rb = 1.02) had the highest strength, closeness, and betweenness in the symptom network 1-2 days after lung cancer surgery. At 5-6 days after surgery, shortness of breath (rs = 27.00) emerged as the symptom with the highest strength, fatigue (rc = 0.04) had the highest closeness, and cough (rb = 1.08) ranked highest in betweenness within the symptom network. CONCLUSION: Fatigue stands out as the most core symptom in the network 1-2 days after lung cancer surgery. Shortness of breath, fatigue and cough are the most core symptoms in the symptom network 5-6 days after surgery. Therefore, clinical staff can improve the postoperative symptom experience of lung cancer patients by developing symptom management programmes tailored to these core symptoms.

Adventitial delivery of miR-145 to treat intimal hyperplasia post vascular injuries through injectable and in-situ self-assembling peptide hydrogels.

Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. To develop a vascular adventitial drug delivery system to treat intimal hyperplasia post vascular injuries, we loaded miR-145-5p-agomir (miR-145) into an injectable and in-situ self-assembling RAD peptide hydrogel. In vitro data showed that the miR-145 could be well incorporated into the RAD peptide hydrogels and released in a slow and controlled manner. The released miR-145 could transfect SMCs successfully, and the transfected SMCs exhibited a reduced migration capacity and higher expressions of SMC contractile biomarkers as compared to the non-transfected SMCs. In vivo data showed that the retention of the miR-145 was greatly elongated by the RAD peptide hydrogels. In addition, the application of the miR-145-loaded RAD peptide hydrogels surrounding injured arteries decreased the proliferative SMCs, promoted the regeneration of endothelium, reduced the macrophage infiltration, inhibited the neointimal formation and prevented adverse ECM remodeling via downregulation of KLF4 expression. The RAD peptide hydrogels loaded with miR-145 can successfully inhibit intimal hyperplasia after vascular injuries and thus hold great potential as an innovative extravascular drug delivery approach to treat vascular diseases. STATEMENT OF SIGNIFICANCE: Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. Our work here demonstrates that the RAD peptide hydrogels loaded with miR-145-5p-agomir (miR-145) can successfully reverse intimal hyperplasia after vascular injuries and thus hold great potential as an innovative vascular adventitial drug delivery approach to treat vascular diseases. Our work proposes a possible paradigm shift from endovascular drug delivery to extravascular drug delivery for vascular disorder treatment.

Dual-Cation CuAgSe-Based Material: Rapid Mass Transfer in Synthesis and High Thermoelectric Performance Realization.

Understanding mass transfer mechanisms is vital for developing new material synthesis and densification technologies. Ion transport, serving both mass and charge transfer, is essential for the rapid preparation of high-performance fast ionic conductor thermoelectric materials like Zn4Sb3 and Cu2Q (Q = S, Se). In the case of dual-cation fast ion conductor materials like CuAgSe, exploring the relationship between cation transport becomes pertinent. In this study, copper (Cu) and selenium (Se) undergo a reaction in the presence of an electric field (∼15 A), resulting in the formation of the CuSe compound. Subsequent to this initial reaction, a subsequent thermal environment facilitates the interaction among Cu, CuSe, and Ag2Se, culminating in the rapid formation and densification of CuAgSe (with a relative density exceeding 99%) in just 30 s. Evidently, the diffusion of copper ions substantiates a pivotal role in facilitating mass transfer. As a result, CuAg1+xSe samples with different silver contents (x = 0.01, 0.02, 0.03, 0.04 and 0.05) can effectively inhibit cation vacancy, and introduce highly ordered Ag nanotwins to enhance the electrical transport performance. For CuAg1.04Se, a peak ZT value of 1.0 can be achieved at 673 K, which is comparable to the literatures. This work will guide the future electric field-assisted rapid mass transfer of materials.

Gamma-ray irradiation as an effective method for mitigating antibiotic resistant bacteria and antibiotic resistance genes in aquatic environments.

The prevalence of antibiotic resistance genes (ARGs) in municipal wastewater treatment plants (MWTPs) has emerged as a significant environmental concern. Despite advanced treatment processes, high levels of ARGs persist in the secondary effluent from MWTPs, posing ongoing environmental risks. This study explores the potential of gamma-ray irradiation as a novel approach for sterilizing antibiotic-resistant bacteria (ARB) and reducing ARGs in MWTP secondary effluent. Our findings reveal that gamma-ray irradiation at an absorbed dose of 1.6 kGy effectively deactivates all culturable bacteria, with no subsequent revival observed after exposure to 6.4 kGy and a 96-h incubation in darkness at room temperature. The removal efficiencies for a range of ARGs, including tetO, tetA, blaTEM-1, sulI, sulII, and tetW, were up to 90.5% with a 25.6 kGy absorbed dose. No resurgence of ARGs was detected after irradiation. Additionally, this study demonstrates a considerable reduction in the abundances of extracellular ARGs, with the transformation efficiencies of extracellular tetracycline and sulfadiazine resistance genes decreasing by 56.3-81.8% after 25.6 kGy irradiation. These results highlight the effectiveness of gamma-ray irradiation as an advanced and promising method for ARB sterilization and ARG reduction in the secondary effluent of MWTPs, offering a potential pathway to mitigate environmental risks associated with antibiotic resistance.