Patient-Derived Tumor Organoids Can Predict the Progression-Free Survival of Patients With Stage IV Colorectal Cancer After Surgery.

BACKGROUND: Recent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid-based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown. OBJECTIVE: This study aimed to explore the prognostic value of patient-derived tumor organoid-based drug tests in patients with stage IV colorectal cancer after surgery. DESIGN: Retrospective cohort study. SETTINGS: Surgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital. PATIENTS: A total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019. INTERVENTIONS: Patient-derived tumor organoid culture and chemotherapeutic drug testing. MAIN OUTCOMES MEASURES: Progression-free survival. RESULTS: According to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84-6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71-7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34-4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61-4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid-based drug test model, which includes the patient-derived tumor organoid-based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001). LIMITATIONS: A single-center cohort study. CONCLUSIONS: Patient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.

First-principles investigation of band offset and charge transfer characteristics at the PE/fluorinated layer interface.

Polymers, especially polyethylene (PE), are widely employed as insulating materials in electrical power transmission systems. However, the insulation still faces the problem of space charge, which distorts the electric field distribution and accelerates electrical aging. Experimental results show that after the fluorination process, less charge injection occurs compared with pure PE. To clarify the mechanism, classical molecular dynamics was employed to build a PE/fluorinated layer interfacial model and first principles calculation was utilized to get the band offset at the interface. The results calculated by both the bulk plus band lineup method and the layer-decomposed density of states method show that the energy band of the fluorinated PE layer is overall lower than that of the PE side, and the band offsets are around 2 eV. Charge transport results based on Marcus theory and kinetic Monte Carlo simulations also show that charge can easily accumulate at the interfacial area under an electric field and the band offset can suppress charge injection. The conduction band offset acts as an energy barrier for the excess electrons at the fluorinated layer side to cross the interface, while the valence band offset has the same effect on hole transport because of the energy barrier caused by the inverted region. Our findings provide a fundamental and theoretical basis for material modification and space charge inhibition.

REACT: Remainder Adaptive Compensation for Domain Adaptive Object Detection.

Domain adaptive object detection (DAOD) aims to infer a robust detector on the target domain with the labelled source datasets. Recent studies utilize a feature extractor shared on the source and target domains to capture the domain-invariant features and the task-relevant information with both feature-alignment constraint and source annotations. However, the feature extractor shared across domains discards partial task-relevant information of the target domain due to the domain gap and lack of target annotations, leading to compromised discrimination capabilities within target domain. To this end, we propose a novel REmainder Adaptive CompensaTion network (REACT) to adaptively compensate the extracted features with the remainder features for generating task-relevant features. The key insight is that the remainder features contain the discarded task-relevant information, so they can be adapted to compensate for the inadequate target features. Especially, REACT introduces an additional remainder branch to regain the remainder features, and then adaptively utilizes them to compensate for the discarded task-relevant information, improving discrimination on the target domain. Extensive experiments over multiple cross-domain adaptation tasks with three baselines demonstrate that our approach gains significant improvements and achieves superior performance compared with highly-optimized state-of-the-art methods.

Failure of Lithium-Ion Batteries Accelerated by Gravity.

The safety concerns surrounding lithium-ion batteries (LIBs) have garnered increasing attention due to their potential to endanger lives and incur significant financial losses. However, the origins of battery failures are diverse, presenting significant challenges in developing safety measures to mitigate accidental catastrophes. In this study, the aging mechanism of LiNi0.5Co0.2Mn0.3O2||graphite-based cylindrical 18,650 LIBs stored at room temperature for two years was investigated. It was found that an uneven distribution of electrolytes can be caused by gravity, leading to temperature variations within the battery. Specifically, it was observed that the temperature at the top of the battery was approximately -0.89 °C higher than at the bottom, correlating with an increase in partial internal resistance. Additionally, upon disassembly and analysis of spent batteries, the most significant damage to electrode materials at the top of the battery was observed. These findings suggest that gravity-induced electrolyte insufficiency exacerbates side reactions, particularly at the top of the battery. This study offers a unique perspective on the safety concerns associated with high-energy-density batteries in long-term and large-scale applications.

Overexpression of soybean microRNA156b enhanced tolerance to phosphorus deficiency and seed yield in Arabidopsis.

microRNAs (miRNAs) are endogenous small RNAs that are key regulatory factors participating in various biological activities such as the signaling of phosphorus deficiency in the plant. Previous studies have shown that miR156 expression was modulated by phosphorus starvation in Arabidopsis and soybean. However, it is not clear whether the over-expression of soybean miR156b (GmmiR156b) can improve a plant's tolerance to phosphorus deficiency and affect yield component traits. In this study, we generated Arabidopsis transgenic lines overexpressing GmmiR156b and investigated the plant's response to phosphorus deficiency. Compared with the wild type, the transgenic Arabidopsis seedlings had longer primary roots and higher phosphorus contents in roots under phosphorus-deficit conditions, but lower fresh weight root/shoot ratios under either phosphorus-deficient or sufficient conditions. Moreover, the GmmiR156b overexpression transgenic lines had higher phosphorus content in shoots of adult plants and grew better than the wide type under phosphorus-deficient conditions, and exhibited increased seed yields as well as strong pleiotropic developmental morphology such as dwarfness, prolonged growth period, bushy shoot/branching, and shorter silique length, suggesting that the transgenic lines were more tolerant to phosphorus deficiency. In addition, the expression level of four SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) genes (i.e., AtSPL4/5/6/15) were markedly suppressed in transgenic plants, indicating that they were the main targets negatively regulated by GmmiR156b (especially AtSPL15) and that the enhanced tolerance to phosphorus deficiency and seed yield is conferred mainly by the miR156-mediated downregulation of AtSPL15.

Treatment of Calcific Insertional Achilles Tendinopathy: Knotless Internal Brace versus Knot-Tying Suture Bridge.

BACKGROUND: This study aimed to compare the knotless internal brace technique and the knot-tying suture bridge technique via the medial approach in the treatment of calcific Achilles tendinopathy. METHODS: The clinical data of 25 cases of calcific Achilles tendinopathy in which nonoperative treatments had failed were retrospectively collected. All the patients received Achilles tendon debridement and Haglund deformity excision through a medial approach, followed by repair using the knotless internal brace technique or the knot-tying suture bridge technique. Pain was evaluated by using the visual analog scale (VAS). The American Orthopedic Foot and Ankle Score (AOFAS) questionnaire was administered preoperatively and postoperatively. RESULTS: The mean follow-up time was 2.6 (range 2-3.5) years. There were no wound complications and no Achilles tendon ruptures. At 1 year postoperatively, the internal brace group was superior to the suture bridge group in terms of the VAS scores (p = 0.003). However, no differences were noticed between the two groups in either the VAS or the AOFAS scores at 2 years postoperatively. CONCLUSIONS: The medial approach in combination with the suture bridge technique was effective in treating calcific Achilles tendinopathy. The knotless internal brace technique involved less pain compared to the knot-tying suture bridge technique only at the early postoperative stage.

Tween-20-Modified BiVO4 Nanorods for CT Imaging-Guided Radiotherapy of Tumor.

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, which seriously threatens the health of patients. At present, radiotherapy is one of the commonly used methods for oral cancer treatment. However, the resistance of cancerous tissues to ionizing radiation, as well as the side effects of X-rays on healthy tissues, still limit the application of radiotherapy. Therefore, how to effectively solve the above problems is still a challenge at present. Generally speaking, elements with high atomic numbers, such as bismuth, tungsten, and iodine, have a high X-ray attenuation capacity. Using nanomaterials containing these elements as radiosensitizers can greatly improve the radiotherapy effect. At the same time, the modification of nanomaterials based on the above elements with the biocompatible polymer can effectively reduce the side effects of radiosensitizers, providing a new method for the realization of efficient and safe radiotherapy for oral cancer. In this work, we prepared Tween-20-modified BiVO4 nanorods (Tw20-BiVO4 NRs) and further used them in the radiotherapy of human tongue squamous cell carcinoma. Tw20-BiVO4 NRs are promising radiosensitizers, which can generate a large number of free radicals under X-rays, leading to the damage of cancer cells and thus playing a role in tumor therapy. In cell experiments, radiotherapy sensitization of Tw20-BiVO4 NRs significantly enhanced the production of free radicals in oral cancer cells, aggravated the destruction of chromosomes, and improved the therapeutic effect of radiotherapy. In animal experiments, the strong X-ray absorption ability of Tw20-BiVO4 NRs makes them effective contrast agents in computed tomography (CT) imaging. After the tumors are located by CT imaging, it helps to apply precise radiotherapy; the growth of subcutaneous tumors in nude mice was significantly inhibited, confirming the remarkable effect of CT imaging-guided radiotherapy.

Cutoff value of IC50 for drug sensitivity in patient-derived tumor organoids in colorectal cancer.

Patient-derived tumor organoids (PDTOs) have the potential to be used to predict the patient response to chemotherapy. However, the cutoff value of the half-maximal inhibition concentration (IC50) for PDTO drug sensitivity has not been validated with clinical cohort data. We established PDTOs and performed a drug test in 277 samples from 242 CRC patients who received FOLFOX or XELOX chemotherapy. After follow-up and comparison of the PDTO drug test and final clinical outcome results, the optimal IC50 cutoff value for PDTO drug sensitivity was 43.26 µmol/L. This PDTO drug test-defined cutoff value could predict patient response with 75.36% sensitivity, 74.68% specificity, and 75% accuracy. Moreover, this value distinguished groups of patients with significant differences in survival benefit. Our study is the first to define the IC50 cutoff value for the PDTO drug test to effectively distinguish CRC patients with chemosensitivity or nonsensitivity and predict survival benefits.

The Application of circRNA-016901 in Improving the Diagnostic Accuracy of Osteoarthritis.

In clinical practice, osteoarthritis (OA) is frequently misdiagnosed as rheumatoid arthritis (RA) and osteonecrosis (ON), leading to wrong treatment and disease progression. Circular RNA- (circRNA-) 016901 affects the recovery of irradiation-induced injury in the bone, while its role in OA is unclear. This study is aimed at exploring the role of circRNA-016901 in improving the diagnostic accuracy of OA. The present study included patients with OA (n = 80), patients with RA (n = 80), patients with ON (n = 80), and healthy controls (HCs, n = 80) to collect plasma samples before and after treatment. RT-qPCR was performed to detect RNA accumulation of circRNA-016901 in plasma samples from all participants. The role of plasma expression of circRNA-016901 in predicting OA was studied with ROC curve analysis. Association between plasma expression of circRNA-016901 and patients' clinical features was analyzed with the chi-squared test. Compared to HCs, increased accumulation of circRNA-016901 was only observed in the OA group, but not in the RA and ON groups before treatment. OA patients were effectively separated from the RA, ON, and HC groups using plasma expression of circRNA-016901 before treatment as a biomarker. Plasma expression of circRNA-016901 was closely associated with OA patients' disease severity. After treatment, decreased plasma expression levels of circRNA-016901 were only observed in OA patients, while no alteration in plasma circRNA-016901 accumulation was observed in the RA and ON groups. In conclusion, circRNA-016901 is accumulated to high levels in OA and may be applied to improve the diagnostic accuracy of OA.

Capillaries segmentation of NIR-II images and its application in ischemic stroke.

Fluorescence imaging in the second near-infrared window (NIR-II) offers µm resolution blood vessel information noninvasively, which is crucial for the diagnosis and surgery treatment of some blood vessel-related diseases. However, only a few blood vessel segmentation algorithms have been done for the NIR-II images so far. Here, we proposed a vessel segmentation algorithm that used multi-scale enhancement and fractional differential to enhance capillaries, and then segmented vessels based on the blood vessels' tubular characteristics. Experimental results showed that this method could effectively suppress the point and lump tissue noise influence during vascular segmentation. The accuracy of vessel identification by other algorithms dropped below 30%, while our algorithm still achieved an accuracy of around 50% in deep vessel segmentation experiments with the 6.5 mm Intralipid. So it had the advantage of accurately detecting deep and dim blood capillaries. Meanwhile, the vascular density quantization algorithm had been successfully applied to the mice's ischemic stroke evaluations for the first time. In addition, this algorithm can provide the quantified vessel features under physiological or pathological conditions, which could be used to accurately evaluate the stroke drugs' therapeutic effect in the future.

PVP-Modified Multifunctional Bi2WO6 Nanosheets for Enhanced CT Imaging and Cancer Radiotherapy.

Malignant tumors are one of the main causes of human death. The clinical treatment of malignant tumors is usually surgery, chemotherapy, radiotherapy, and so forth. Radiotherapy, as a traditional and effective treatment method for cancer, is widely used in clinical practice, but the radiation resistance of tumor cells and the toxic side effects to normal cells are still the Achilles heel of radiotherapy. Multifunctional inorganic high-atom nanomaterials are expected to enhance the effect of tumor radiotherapy. Tungsten and bismuth, which contain elements with high atomic coefficients, have strong X-ray energy attenuation capability. We synthesized Bi2WO6 nanosheets (NSs) using a hydrothermal synthesis method and modified polyvinylpyrrolidone (PVP) on their surface to make them more stable. PVP-Bi2WO6 NSs have a variety of effects after absorbing X-rays (such as the photoelectric effect and Compton effect) and release a variety of particles such as photoelectrons, Compton electrons, auger electrons, and so forth, which can react with organic molecules or water in cells, generate a large number of free radicals, and promote cell apoptosis, thereby improving the effect of radiotherapy. We show through γ-H2AX and DCFH-DA probe analysis experiments that PVP-Bi2WO6 NSs can effectively increase cell DNA damage and reactive oxygen species formation under X-ray irradiation. Clone formation analysis showed that PVP-Bi2WO6 NSs can effectively suppress cell colony formation under X-ray irradiation. These versatile functions endow PVP-Bi2WO6 NSs with enhanced radiotherapy efficacy in animal models. In addition, PVP-Bi2WO6 NSs can also be used as contrast agents for X-ray computed tomography (CT) imaging with obvious effects. Therefore, PVP-Bi2WO6 NSs can be used as CT imaging contrast agents and tumor radiotherapy sensitizers and have potential medical applications.

Acceptor engineering for NIR-II dyes with high photochemical and biomedical performance.

It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alkaline conditions, compared with conventional NIR-II building block benzobisthiadiazole (BBT) and 6,7-diphenyl-[1,2,5] thiadiazolo[3,4-g]quinoxaline (PTQ). The sulfonated hydrophilic dye, FT-TQT, is further synthesized with 2.13-fold increased quantum yield than its counterpart FT-BBT with BBT as acceptor. FT-TQT complexed with FBS is also prepared and displays a 16-fold increase in fluorescence intensity compared to FT-TQT alone. It demonstrates real-time cerebral and tumor vessel imaging capability with µm-scale resolution. Dynamic monitoring of tumor vascular disruption after drug treatment is achieved by NIR-II fluorescent imaging. Overall, TQT is an efficient electron acceptor for designing innovative NIR-II dyes. The acceptor engineering strategy provides a promising approach to design next generation of NIR-II fluorophores which open new biomedical applications.

Evaluation of Pulmonary Edema Using Ultrasound Imaging in Patients With COVID-19 Pneumonia Based on a Non-local Channel Attention ResNet.

Recent research has revealed that COVID-19 pneumonia is often accompanied by pulmonary edema. Pulmonary edema is a manifestation of acute lung injury (ALI), and may progress to hypoxemia and potentially acute respiratory distress syndrome (ARDS), which have higher mortality. Precise classification of the degree of pulmonary edema in patients is of great significance in choosing a treatment plan and improving the chance of survival. Here we propose a deep learning neural network named Non-local Channel Attention ResNet to analyze the lung ultrasound images and automatically score the degree of pulmonary edema of patients with COVID-19 pneumonia. The proposed method was designed by combining the ResNet with the non-local module and the channel attention mechanism. The non-local module was used to extract the information on characteristics of A-lines and B-lines, on the basis of which the degree of pulmonary edema could be defined. The channel attention mechanism was used to assign weights to decisive channels. The data set contains 2220 lung ultrasound images provided by Huoshenshan Hospital, Wuhan, China, of which 2062 effective images with accurate scores assigned by two experienced clinicians were used in the experiment. The experimental results indicated that our method achieved high accuracy in classifying the degree of pulmonary edema in patients with COVID-19 pneumonia by comparison with previous deep learning methods, indicating its potential to monitor patients with COVID-19 pneumonia.

Two dimensional self-assembly zinc porphyrin and zinc phthalocyanine heterojunctions with record high power conversion efficiencies.

Compared to inorganic solar cells, the power conversion efficiencies (PCEs) of organic solar cells are much lower, but they are compensated by many merits such as lower cost, less weight, and tunable structures, making them prospective for further applications. Porphyrin and phthalocyanine are the two most significant materials for organic solar cells due to their strong light-absorbing properties and semiconductor characteristics. However, there is little research on the 2D heterojunction solar cells based on these two materials, meanwhile the PCEs of them are still low. Here we have self-assembled several 2D zinc porphyrins (ZnPors) and performed first-principles simulation to demonstrate their good stability, suitable light harvesting, and high charge carrier mobility. By perfectly matching lattice constants and molecular energy levels between those 2D ZnPors and our previous proposed zinc phthalocyanines (ZnPcs), 11 type-II organic heterojunctions are constructed to further improve their charge separation capability. Those advantages endow 2D ZnPors and ZnPcs appreciable PCEs for solar cells. Among them, the theoretical PCE of 2D ZnPors/ZnPcs heterojunctions achieves as high as 19.84%, which exceeds all reported organic solar cells, and even approaches the PCEs of inorganic solar cells. These results indicate that our 2D ZnPors and 2D ZnPcs are good candidate materials for future organic solar cells.