Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy.

The antitumor strategies based on innate immunity activation have become favored by researchers in recent years. In particular, strategies targeting antiphagocytic signaling blockade to enhance phagocytosis have been widely reported. For example, the addition of prophagocytic signals such as calreticulin could make the strategy significantly more effective. In this study, an antitumor strategy that combines photodynamic therapy (PDT) with CD47 blockade has been reported. This approach promotes the maturation of dendritic cells and the presentation of tumor antigens by PDT-mediated tumor immunogenic cell death, as well as the enhancement of cytotoxic T lymphocyte infiltration in tumor areas and the phagocytic activity of phagocytes. Furthermore, the downregulation and blockage of CD47 protein could further promote phagocytic activity, strengthen the innate immune system, and ultimately elevate the antitumor efficacy and inhibit tumor metastasis.

Ultra-high-precision pneumatic force servo system based on a novel improved particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory.

In this study, an ultra-high-precision pneumatic force servo system (UPFSS) is proposed. On the one hand, a novel air-floating pneumatic cylinder (AFPC) with an air-floating piston capable of independent air supply and exhaust is developed for this system, and its special flow channel design allows the air-floating piston to be suspended in the cylinder without being constrained by the pressure in the chambers. The friction force of the AFPC is less than 0.0049 N. On the other hand, a leakage chamber is constructed to simulate the clearance between the air-floating piston and the cylinder wall, and a fuzzy proportional integral (FPI)-based pressure control system (PCS) is designed for the simulated leakage chamber. Furthermore, a novel particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory (IGF-PSO) is presented. After testing, the IGF-PSO algorithm is found to have outstanding optimization performance. Then, the parameters of the FPI controller are optimized through the IGFPSO algorithm. Experimental comparisons reveal that the steady-state error achieved by the parameter-optimized pressure controller in response to the leakage condition is about 38 % smaller than that achieved by the pressure controller with parameters obtained using the trial-and-error method. Finally, the UPFSS is tested by using the optimized PCS to supply compressed air to the chamber of the AFPC. The results show that the UPFSS achieves a steady-state error of no more than 0.0279 N in the continuous step response within the range of 240 N.

Biomechanical design optimization and experimental verification of Bezier curve based two-sectional cervical pillow with variable-density cellular structure.

The fundamental function of an optimal cervical pillow is to provide sufficient support to maintain normal spinal alignment and minimize biological stress on the contact surface throughout sleep. The recent advancements in cervical pillows have mainly focused on the subjective and objective evaluations of support comfort, as well as the relationship between pillow height and cervical vertebrae posture. However, only a few studies have addressed shape design guidelines and mechanical performances of the pillows themselves. In this study, a two-sectional contour cervical pillow comprising an arc and a Bezier curve is designed to support the head and neck. The design of the arc-shaped neck section incorporates the Cobb's angle and Borden value from healthy individuals to reflect the consistency of normal cervical anatomical features. The Bezier curve-based head section takes the head length and neck depth into account as significant individual differences. Static analysis and lattice optimization are performed in ANSYS Workbench to develop a variable-density cellular structure, aimed at improving air permeability and reducing the risk of pressure ulcers associated with the cervical pillow. The rapid prototyping technique fused deposition modeling (FDM) and thermoplastic material polylactic acid (PLA) are employed for fabricating different cellular structures. The results demonstrate that the neck section experiences less stress and greater deformation in comparison to the head section, indicating good comfort and support provided by the designed cervical pillow. Additionally, the compressive, bending, and cushion properties of the 3D-printed cervical pillow with variable-density cellular structure are experimentally validated, further confirming its effectiveness.

Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. METHODS: Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

Achieving Non-Interfacial Blocking Zinc Ion Transport Based on MOF Derived Manganese Oxides and Amorphous Carbon Hybrid Materials.

How to coordinate electron and ion transport behavior across scales and interfaces within ion battery electrodes? The exponential increase in surface area observed in nanoscale electrode materials results in an incomprehensibly vast spatial interval. Herein, to address the problems of volume expansion, dissolution of cathode material, and the charge accumulation problem existing in manganiferous materials for zinc ion batteries, metal organic framework is utilized to form the architecture of non-interfacial blocking ~10 nm Mn2O3 nanoparticles and amorphous carbon hybrid electrode materials, demonstrating a high specific capacity of 361 mAh g-1 (0.1 A g-1), and excellent cycle stability of 105 mAh g-1 after 2000 cycles under 1 A g-1. The uniform and non-separated disposition of Mn and C atoms constitutes an interconnected network with high electronic and ionic conductivity, minimizing issues like structural collapse and volume expansion of the electrode material during cycling. The cooperative insert mechanism of H+ and Zn2+ are analyzed via ex-situ XRD and in-situ Raman tests. The model battery is assembled to present practical possibilities. The results indicate that MOF-derived carbonization provides an effective strategy for exploring Mn-based electrode materials with high ion and electron transport capacity.

Dynamic updated key distribution encryption scheme with the wireless rate of 102†Gb/s based on a syncretic W band-PON transmission system.

In this paper, a dynamic updated key distribution encryption scheme based on syncretic W band-passive optical network (PON) is proposed. The 102 Gb/s encrypted data rate using 64QAM is successfully transmitted over the 50 m wireless distance under 15% soft-decision forward error correction (SD-FEC) for a pre-FEC bit error rate (BER) threshold of 1.56 × 10-2. The scheme can realize an error-free public key transmission and public key updates up to 1014 times. In the encryption transmission system, there is a small deviation of the private key, and the received BER is more than 0.45. As far as we know, this is the first time to complete a dynamic key distribution based on a syncretic W band-PON system.

Effects of microplastics and combined pollution of polystyrene and di-n-octyl phthalate on photosynthesis of cucumber (Cucumis sativus L.).

Photosynthesis provides carbon sources and energy for crop growth and development, and the widespread presence of microplastics and plastic plasticisers in agricultural soils affects crop photosynthesis, but the mechanism of the effect is not clear. This study aims to investigate the effects of different microplastics and plasticizers on cucumber photosynthesis. Using polyvinyl chloride (PVC), polyethylene (PE), polystyrene (PS), and di-n-octyl phthalate (DOP) as representative microplastics and plasticizers, we assessed their impact on cucumber photosynthesis. Our results reveal significant alterations in key parameters: intercellular CO2 concentration (Ci) and transpiration rate (Tr) increased across all treatments, whereas stomatal limit value (Ls) and water use efficiency (WUE) decreased. Notably, PS + DOP treatment led to a significant reduction in the maximum efficiency of photosystem II (Fv/Fm) and ATP accumulation. Furthermore, PE and PS + DOP treatments decreased lycopene and ɛ-carotene synthesis rates, as well as abscisic acid (ABA) accumulation. All treatments inhibited the conversion of ß-carotene into strigolactone (SL) and decreased chlorophyll synthesis rates, with PS + DOP exhibiting the most severe impact. Regarding chlorophyll degradation pathways, PVC and PE treatments reduced chlorophyll decomposition rates, whereas DOP with PS promoted degradation. PE and PS treatments also impaired light energy capture, electron transport, and the structural stability of photosystems I and II, as well as photosynthetic capacity and NADPH and ATP synthesis rates. Our findings underscore the differential impacts of microplastics and plasticizers on cucumber photosynthesis, with PS + DOP having the most detrimental effect. These results shed light on the complex interactions between microplastics and plant physiology, highlighting the urgent need for mitigation strategies in agricultural practices to safeguard crop productivity and environmental sustainability.

Construction of ecological security pattern of arid area based on landscape ecological risk assessment: a case study of the Wu-Chang-Shi urban agglomeration.

The construction of ecological security pattern (ESP) holds paramount importance in ensuring regional environment sustainability. This study introduces an innovative approach to ESP construction grounded in landscape ecological risk (LER) assessment, with Wu-Chang-Shi urban agglomeration in Xinjiang, China, serving as a case study. Initially, LER within the area was evaluated using the LER Index (LERI) method. Subsequently, the Geodetector model was employed to discern the relationship between multi-source data and LER. Furthermore, ecological resistance and corridors were delineated utilizing the minimum cumulative resistance (MCR) model. Lastly, the corridors were optimized using the gravity model, finalizing the ESP construction. Study results reveal that LER was always fluctuating from 1990 to 2010, and tended to stabilize from 2010 to 2020. Factor detection underscores the predominant influence of land use on LER, followed by elevation and vegetation distribution. The ESP shows the imperative for improving connectivity of the natural areas that are fragmented by urban land, highlighting the great significance of the woodland-originating corridors. Finally, strategies are proposed to enhance woodland and water coverage, boost landscape diversity in nature reserves, and prioritize ecological conservation in corridor regions. In summation, the study furnishes a framework for analyzing arid regions in Eurasia. Furthermore, the research idea of evaluation-analysis-remodeling also offers insights into environmental management in developing areas with more diverse climate types.

Automated Design of Collaboration-Based Hybrid Metaheuristics.

Hybridization plays a prominent role in bolstering the performance of optimization algorithms (OAs), yet designing efficient hybrid OAs tailored to intricate optimization problems persists as a formidable task. This article introduces a novel top-down methodology for the automated design of hybrid OAs, treating algorithm design as a meta-optimization problem. A general design template for collaboration-based hybrid OAs is developed, integrating a multitude of hybridization strategies for the first time. Besides, a mathematical model is built to formulate the meta-optimization problem of algorithm design. To address the meta-optimization challenge, an improved multifactorial evolutionary algorithm is proposed to automatically design efficient hybrid metaheuristics in a multitasking environment for the given instances with diverse features. To verify the effectiveness of the proposed design methodology, it is applied to the CEC2017 benchmark functions and the binary knapsack problem. Numerical results have demonstrated the feasibility and effectiveness of the proposed methodology for both continuous and combinatorial optimization benchmarks.

A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling.

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

Model-Informed individualized dosage regimen of sirolimus in pediatric patients with intractable lymphatic malformations.

Intractable lymphatic malformations (iLM) pose a significant threat to affected children, demonstrating limited responses to conventional treatments. Sirolimus, effectively inhibiting endothelial cell proliferation in lymphatic vessels, plays a crucial role in iLM treatment. However, the drug's narrow therapeutic window and substantial interindividual variability necessitate customized dosing strategies. This study aims to establish a Population Pharmacokinetic Model (PopPK model) for sirolimus in pediatric iLM patients, identifying quantitative relationships between covariates and sirolimus clearance and volume of distribution. Initial dosages are recommended based on a target concentration range of 5-15 ng/mL. Retrospective data from our institution, encompassing 53 pediatric patients with 275 blood concentration results over the past five years (average age: 4.64 ± 4.19 years), constituted the foundation of this analysis. The final model, adopting a first-order absorption and elimination single-compartment model, retained age as the sole covariate. Results indicated a robust correlation between apparent clearance (CL/F) at 5.56 L/h, apparent volume of distribution (V/F) at 292.57 L, and age. Monte Carlo simulation guided initial dosages for patients aged 0-18 years within the target concentration range. This study presents the first PopPK model using a large Therapeutic Drug Monitoring (TDM) database to describe personalized sirolimus dosing for pediatric iLM patients, contributing to pharmacokinetic guidance and potentially improving long-term clinical outcomes.

Real-world evidence of a novel tetravalent immunoglobulin Y effectiveness and safety in patients with the refractory Helicobacter pylori infection.

BACKGROUND: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. METHODS: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting13. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. RESULTS: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of 13C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. CONCLUSIONS: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.

The GgcxK325Q Mutation Does Not Affect the Calcium Homeostasis of the Epididymis and Male Fertility in Mice.

A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), the carboxylation enzyme of the matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm maturation in rats and that the GGCX SNP mutation rs699664 was associated with asthenozoospermia (AZS) in humans. Here, we investigated the expression patterns of GGCX and MGP in the mouse epididymis and generated GgcxK325Q knock-in (KI) mice. We also tested the effects of this mutation on epididymal calcium homeostasis, sperm function, and male fertility in GgcxK325Q-/- mice. The results showed that both GGCX and MGP were enriched in all regions of the mouse epididymis, especially in the initial segment of the epididymis. Double immunofluorescence staining revealed that GGCX colocalized with MGP in the epithelial cells of the initial segment and caput regions as well as in the lumen of the corpus and cauda regions of the mouse epididymis. However, the GgcxK325Q-/- mice were fertile with normal epididymal morphology, sperm functions, and epididymal calcium concentration. Overall, our findings revealed that the GgcxK325Q mutation does not exert any discernible effect on male fertility in mice.

Nab-paclitaxel plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.

PURPOSE: This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer. METHODS: Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset. RESULTS: The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05). CONCLUSION: Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer.

Development and Validation of a Clinic Machine Learning Classifier for the Prediction of Risk Stratifications of Prostate Cancer Bone Metastasis Progression to Castration Resistance.

Objective: To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance. Methods: Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5-28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901-0.991] and 0.927[95% CI: 0.864-0.990] in the training and validation cohort, respectively. Conclusion: After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making.

A new strategy for overcoming drug resistance in liver cancer: Epigenetic regulation.

Drug resistance in hepatocellular carcinoma has posed significant obstacles to effective treatment. Recent evidence indicates that, in addition to traditional gene mutations, epigenetic recoding plays a crucial role in HCC drug resistance. Unlike irreversible gene mutations, epigenetic changes are reversible, offering a promising avenue for preventing and overcoming drug resistance in liver cancer. This review focuses on various epigenetic modifications relevant to drug resistance in HCC and their underlying mechanisms. Additionally, we introduce current clinical epigenetic drugs and clinical trials of these drugs as regulators of drug resistance in other solid tumors. Although there is no clinical study to prevent the occurrence of drug resistance in liver cancer, the development of liquid biopsy and other technologies has provided a bridge to achieve this goal.

Accurate Prediction of the Magnetic Ordering Temperature of Ultralow-Temperature Magnetic Refrigerants.

Adiabatic demagnetization refrigeration is known to be the only cryogenic refrigeration technology that can achieve ultralow temperatures (≪1 K) at gravity-free conditions. The key indexes to evaluate the performance of magnetic refrigerants are their magnetic entropy changes (-ΔSm) and magnetic ordering temperature (T0). Although, based on the factors affecting the -ΔSm of magnetic refrigerants, one has been able to judge if a magnetic refrigerant has a large -ΔSm, how to accurately predict their T0 remains a huge challenge due to the fact that the T0 of magnetic refrigerants is related to not only magnetic exchange but also single-ion anisotropy and magnetic dipole interaction. Here, we, taking GdCO3F (1), Gd(HCOO)F2, Gd2(SO4)3·8H2O, GdF3, Gd(HCOO)3 and Gd(OH)3 as examples, demonstrate that the T0 of magnetic refrigerants with very weak magnetic interactions and small anisotropy can be accurately predicted by integrating mean-field approximation with quantum Monte Carlo simulations, providing an effective method for predicting the T0 of ultralow-temperature magnetic refrigerants. Thus, the present work lays a solid foundation for the rational design and preparation of ultralow-temperature magnetic refrigerants in the future.