Artesunate inhibits vasculogenic mimicry in choroidal melanoma through HIF-1 α/ VEGF/PDGF pathway.

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

Enhancing practicality of deep learning for crop disease identification under field conditions: insights from model evaluation and crop-specific approaches.

BACKGROUND: Crop diseases can lead to significant yield losses and food shortages if not promptly identified and managed by farmers. With the advancements in convolutional neural networks (CNN) and the widespread availability of smartphones, automated and accurate identification of crop diseases has become feasible. However, although previous studies have achieved high accuracy (>95%) under laboratory conditions (Lab) using mixed data sets of multiple crops, these models often falter when deployed under field conditions (Field). In this study, we aimed to evaluate disease identification accuracy under Lab, Field, and Mixed (Lab and Field) conditions using an assembled data set encompassing 14 diseases of apple (Malus × domestica Borkh.), potato (Solanum tuberosum L.), and tomato (Solanum lycopersicum L.). In addition, we investigated the impact of model architectures, parameter sizes, and crop-specific models (CSMs) on accuracy, using DenseNets, ResNets, MobileNetV3, EfficientNet, and VGG Nets. RESULTS: Our results revealed a decrease in accuracy across all models from Lab (98.22%) to Mixed (91.76%) to Field (71.55%) conditions. Interestingly, disease classification accuracy showed minimal variation across model architectures and parameter sizes: Lab (97.61-98.76%), Mixed (90.76-92.31%), and Field (68.56-73.81%). Although CSMs were found to reduce inter-crop disease misclassifications, they also led to a slight increase in intra-crop misclassifications. CONCLUSION: Our findings underscore the importance of enriching data representation and volumes over employing new model architectures. Furthermore, the need for more field-specific images was highlighted. Ultimately, these insights contribute to the advancement of crop disease identification applications, facilitating their practical implementation in farmer's fields. © 2024 Society of Chemical Industry.

Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.

While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding. Primary endpoints included safety, maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary objectives included preliminary clinical activity and correlative studies from biospecimens. 2141-V11 was well-tolerated without dose-limiting toxicities and MTD was not reached. In ten evaluable patients with metastatic cancer, the overall response rate was 20%, with complete responses in two patients (melanoma and breast carcinoma) and stable disease in six patients. 2141-V11 induced tumor regression in injected and non-injected lesions, with increased leukocyte infiltration and tertiary lymphoid structures (TLS) formation in post-treatment biopsies. In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588).

Shearing brittle intermetallics enhances cryogenic strength and ductility of steels.

Precipitates are crucial for crafting mechanically strong metallic materials. In this work, we report the dislocation cutting of B2 (ordered body-centered cubic) nanoprecipitates, typically considered nonshearable intermetallics, in a lightweight compositionally complex steel during cryogenic tensile loading. Shearing is enabled by the high strength level for dislocation glide within the austenitic matrix, attributed to the substantial strengthening from subnanoscale local chemical ordering zones and the pronounced solid solution strengthening from the multiprincipal elements in the matrix. This mechanism not only harnesses the intense strengthening and strain hardening provided by otherwise impenetrable brittle nanoprecipitates but also introduces ductility through their sequential shearing with ongoing deformation. Our steel thus showcases ultrahigh cryogenic tensile strength up to 2 gigapascal at a remarkable tensile elongation of 34%. This study reveals a new strategy for designing high-performance structural materials.

Immunogenicity evaluation of primary polio vaccination schedule with inactivated poliovirus vaccines and bivalent oral poliovirus vaccine.

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.

Functional UiO-66 for highly selective adsorption of N-nitrosodipropylamine: adsorption performance and mechanisms.

N-Nitrosodipropylamine (NDPA) is a class of nitrogenous disinfection by-products (N-DBPs) with high toxicity. Although NDPA present in water bodies is at relatively low concentrations, the potential risk is high due to its high toxicity and bioaccumulation. Metal-organic frameworks (MOFs), a new type of porous material with remarkable functionality, have shown great performance in a wide variety of applications in adsorption. This is the first study investigating the adsorption of MOFs on NDPA. Herein, UiO-66 with -NH2 and imidazolium functional groups were synthesized by modifying UiO-66 after amination. Adsorption kinetics and isotherm models were used to compare the adsorption properties of the two materials for low-concentration NDPA in water. The results showed that the behavior of all the adsorbents was consistent with the Langmuir model and the pseudo-second-order model and that the adsorption was homogeneous chemisorption. The structures of the nanoparticles were characterized by FTIR, zeta potential, XRD, SEM and BET measurements. Based on the characteristics, four adsorption mechanisms, namely electron conjugation, coordination reaction, anion-π interaction, and van der Waals forces, were simultaneously involved in the adsorption. The influencing factor experiment revealed that the adsorption of UiO-66-NH2 and (I-)Meim-UiO-66 involved hydrogen bonding and electrostatic interactions, respectively.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy.

AIM: To observe the therapeutic effect of conbercept on diabetic macular edema (DME) complicated with diabetic nephropathy (DN). METHODS: In this retrospective study, 54 patients (54 eyes) that diagnosed as DME from January 2017 to October 2021 were collected. The patients were divided into two groups: DME patients with DN (25 eyes), and DME patients without DN (29 eyes). General conditions were collected before treatment, laboratory tests include fasting blood glucose, HbA1c, microalbumin/creatinine, serum creatinine. Optical coherence tomography (OCT) was used to check the ellipsoidal zone (EZ) and external limiting membrane (ELM) integrity. Central macular thickness (CMT), best corrected visual acuity (BCVA), and retinal hyperreflective foci (HF) as well as numbers of injections were recorded. RESULTS: There were significant differences between fasting blood glucose, HbA1c, serum creatinine, urinary microalbumin/creatinine, and estimated glomerular filtration rate (eGFR) between the two groups (all P<0.05). EZ and ELM continuity in the DME+DN group was worse than that in the DME group (P<0.05). BCVA (logMAR) in the DME group was significantly better than that in the DME+DN group at the same time points during treatment (all P<0.05). CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points (all P<0.05) and significantly decreased in both groups with time during treatment. At 6mo after treatment, the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86, respectively. CONCLUSION: Conbercept has a significant effect in short-term treatment of DME patients with or without DN, and can significantly ameliorate BCVA, CMT and the number of HF, treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Identification of associated risk factors for serological distribution of hepatitis B virus via machine learning models.

BACKGROUND: The provincial-level sero-survey was launched to learn the updated seroprevalence of hepatitis B virus (HBV) infection in the general population aged 1-69 years in Chongqing and to assess the risk factors for HBV infection to effectively screen persons with chronic hepatitis B (CHB). METHODS: A total of 1828 individuals aged 1-69 years were investigated, and hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), and antibody to B core antigen (HBcAb) were detected. Logistic regression and three machine learning (ML) algorithms, including random forest (RF), support vector machine (SVM), and stochastic gradient boosting (SGB), were developed for analysis. RESULTS: The HBsAg prevalence of the total population was 3.83%, and among persons aged 1-14 years and 15-69 years, it was 0.24% and 4.89%, respectively. A large figure of 95.18% (770/809) of adults was unaware of their occult HBV infection. Age, region, and immunization history were found to be statistically associated with HBcAb prevalence with a logistic regression model. The prediction accuracies were 0.717, 0.727, and 0.725 for the proposed RF, SVM, and SGB models, respectively. CONCLUSIONS: The logistic regression integrated with ML models could helpfully screen the risk factors for HBV infection and identify high-risk populations with CHB.

Deep evolutionary fusion neural network: a new prediction standard for infectious disease incidence rates.

BACKGROUND: Previously, many methods have been used to predict the incidence trends of infectious diseases. There are numerous methods for predicting the incidence trends of infectious diseases, and they have exhibited varying degrees of success. However, there are a lack of prediction benchmarks that integrate linear and nonlinear methods and effectively use internet data. The aim of this paper is to develop a prediction model of the incidence rate of infectious diseases that integrates multiple methods and multisource data, realizing ground-breaking research. RESULTS: The infectious disease dataset is from an official release and includes four national and three regional datasets. The Baidu index platform provides internet data. We choose a single model (seasonal autoregressive integrated moving average (SARIMA), nonlinear autoregressive neural network (NAR), and long short-term memory (LSTM)) and a deep evolutionary fusion neural network (DEFNN). The DEFNN is built using the idea of neural evolution and fusion, and the DEFNN + is built using multisource data. We compare the model accuracy on reference group data and validate the model generalizability on external data. (1) The loss of SA-LSTM in the reference group dataset is 0.4919, which is significantly better than that of other single models. (2) The loss values of SA-LSTM on the national and regional external datasets are 0.9666, 1.2437, 0.2472, 0.7239, 1.4026, and 0.6868. (3) When multisource indices are added to the national dataset, the loss of the DEFNN + increases to 0.4212, 0.8218, 1.0331, and 0.8575. CONCLUSIONS: We propose an SA-LSTM optimization model with good accuracy and generalizability based on the concept of multiple methods and multiple data fusion. DEFNN enriches and supplements infectious disease prediction methodologies, can serve as a new benchmark for future infectious disease predictions and provides a reference for the prediction of the incidence rates of various infectious diseases.

A trinary support of Ni/NiO/C to immobilize Ir nanoclusters for alkaline hydrogen oxidation.

The hydrogen oxidation reaction is an important process in anion exchange membrane fuel cells with alkaline solutions. The pursuit of efficient catalysts for alkaline hydrogen oxidation has attracted considerable attention. In this study, we present a precursor route for the synthesis of a new Ir-based catalyst (Ir-Ni/NiO/C), in which Ir nanoclusters were immobilized on the generated Ni/NiO/C support derived from a metal-organic framework. The small size of Ir clusters facilitates the exposure of catalytically active sites. The electronic interplay between the Ir nanoclusters and the Ni/NiO/C support optimized the hydrogen binding energy (HBE) and hydroxide binding energy (OHBE) on the surface, which is unattainable on the contrasting Ir-C, Ir-Ni/C, and Ir-NiO/C products. The optimized catalyst shows excellent mass activity for alkaline hydrogen oxidation, which is 3.1 times that of the Pt/C catalyst. This study presents a promising pathway for the development of advanced HOR catalysts.

Resistance training combined with ß-hydroxy ß-methylbutyrate for patients with critical illness: A four-arm, mixed-methods, feasibility randomised controlled trial.

OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.

Iodine status of school-aged children in the changing context of universal salt iodization program during 1997-2018 in Chongqing, China.

OBJECTIVE: To illustrate the changes of iodized salt usage, goiter rate of school-aged children and median urinary iodine concentration (MUIC) of school-aged children in Chongqing for the last 21 years. This study aims to estimate the variational provincial status of iodine nutrition and provide scientific evidence for fine-tuning and adaptation of the current program. METHODS: Different number of families and school children aged 8-10 years from Chongqing during 1997-2018 participated in the study. UIC and iodine content in table salt were measured. Thyroid volumes of students were examined and goiter prevalence was calculated across years. RESULTS: The median iodine content of table salt was negatively associated with years(r = -0.727, P < 0.01). The MUIC were decreased annually (ranged between 200 and 300 µg/L) and was negatively associated with year(r = -0.831, P < 0.01). Goiter of school-aged children in Chongqing was decreased from the highest rate of 23.58% in 1999 to 1.62% in 2018(Cochran-Armitage Trend Test: χ2=-30.695, P < 0.01). Thyroid volume were negatively associated with years(r = -0.962, P < 0.01) and had a positive relationship with MUIC 1997-2018 (r = 0.862, P < 0.01). CONCLUSIONS: The consumption of adequately iodized salt can eliminate Iodine deficiency disorders (IDD) in children, but possible excessive iodine intake from salt could result in high urinary iodine excretion and even goiter. A systematic, well-designed and continual program monitoring is essential to ensure the adequacy of iodine fortification levels and to regularly change the iodine concentration in household table salt.

Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

Trade-offs inside the black box of neoantigen prediction.

Success of precision neoantigen-based immunotherapies hinges on the selection of immunogenic neoantigens, yet currently neither large-scale datasets nor streamlined methods are available to achieve this goal. Müller et al. present a large experimental dataset resource along with machine learning-based models to classify immunogenic neoantigens.

Biomechanical Analysis of Titanium Dental Implants in the All-on-4 Treatment with Different Implant-Abutment Connections: A Three-Dimensional Finite Element Study.

The type of implant-abutment connection is one of the factors influencing the distribution of occlusal forces. This study aims to investigate the biomechanical performance of the mandibular all-on-4 treatment with different implant-abutment connections. Two connection types with 30° abutments and 18-mm implant fixtures were chosen for the posterior implants of the all-on-4 assembly. For the external hexagon connection (EHC) group, the implants with 4 mm in diameter were used. For the internal hexagon connection (IHC) group, we selected implants with 4.3 mm in diameter. A vertical force of 190 N was applied to the cantilever region. The FEA results indicated that the most stressed region in the two groups was prosthetic screws, followed by multi-unit abutments (MUAs). The lowest values of von Mises stress were both observed on the bone. The peak stress value of the implant screw and implant fixture in the EHC group were 37.75% and 33.03% lower than the IHC group, respectively. For stress distribution patterns, the load force tended to be concentrated at locations where components were interconnected. The EHC and IHC are clinically durable under the tested loading conditions, but the prosthetic screws and MUAs can be the weak point on the posterior implant within the mandibular all-on-four assembly. The peak stress values of implant screw and implant fixture in the EHC groups were lower than the IHC group.

Rapid and visual detection of Toxoplasma gondii oocyst in cat feces using loop-mediated isothermal amplification (LAMP) assay.

Toxoplasma gondii is an obligate parasitic protozoon that transmits to animals and humans via ingested food. Cats that act as T. gondii's final hosts play a critical role in T. gondii transmission by shedding millions of oocysts. Timely diagnosis of infected cats is essential for preventing toxoplasmosis because oocysts are a putative T. gondii source in epidemiology. We developed a new visual LAMP assay targeting the B1 gene to analyze single oocysts in cat feces in this study. The amplification result could be visually estimated based on the color change. LAMP assay analytical sensitivity was 101 copies/µL for the B1 gene plasmid, which was tenfold better than the PCR reaction. There were no cross-reactions with other parasites. The LAMP assay can detect a single T. gondii oocyst in 200 mg of cat feces. The LAMP assay detected a single oocyst in 200 mg cat feces at a higher rate than the PCR assay (83.3% vs. 50.0%).

Enhancing Temperature Adaptability of Aqueous Zinc Batteries via Antifreezing Electrolyte and Site-Selective ZnSe-Ag Interface Layer Design.

Rechargeable aqueous zinc batteries (RAZBs) represent a sustainable, environmentally benign, cost-efficient energy storage solution for the scaled renewable power system. However, the cycling endurance and temperature adaptability of RAZBs are hindered by practical technological barriers such as the subzero freezing point of aqueous electrolyte, severe cation dissolution of the cathode, and dendrite growth on the Zn anode. Herein, we optimize the hybrid electrolyte formulation of 8 M ZnCl2 in the ethylene glycol-water mixed solvent to reconfigure the hydrogen bonding and [Zn(H2O)1.80(EG)0.23]2+ solvation sheath, which well balances the ionic conductivity and the antifreezing property until -125 °C. As monitored by operando X-ray diffraction, meanwhile, the structural dissolution of the V2O5 cathode upon the dynamic cycling and static idling storage at elevated temperature are effectively restrained. At the anode side, the thermally induced substitution between the Ag2Se overcoating and Zn foil in situ constructs the site-selective, mosaic interface layer, in which the solvophilic ZnSe facilitates the desolvation, while the Ag species provide zincophilic nucleation sites for high-throughput Zn deposition. The synergistic coupling of the antifreezing electrolyte and anode interfacial design enables the wide-temperature-range adaptability of the RAZB prototype (10 µm Zn foil and 1 mAh cm-2 V2O5 cathode), which balances the cycling endurance (92.5% capacity retention rate for 1000 cycles), 84.7% mitigation of the self-discharge rate at 55 °C, as well as the secured cyclability even at -40 °C.