Artificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer.

Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

Preparation and characterization of tannin-maltodextrin-polyvinyl alcohol hydrogel based on hydrogen bonding for wound healing.

The development of multifunctional and low-cost hydrogel dressings with good mechanical properties, antibacterial activity, and nontoxicity is of great relevance in healthcare. This study aimed to prepare a series of hydrogels consisting of maltodextrin (MD), polyvinyl alcohol (PVA), and tannic acid (TA) through a freeze-thaw cycling technique. Micro-acid hydrogels with different mass ratios (0, 0.25, 0.5, and 1 wt%) were obtained by adjusting the TA content. Among all hydrogels, TA-MP2 hydrogels (with a TA content of 0.5 wt%) showed good physicochemical and mechanical properties. In addition, the biocompatibility of TA-MP2 hydrogels was confirmed by the high cell survival rate of NIH3T3 cells, which was over 90% after 24 h and 48 h of incubation. Additionally, TA-MP2 hydrogels showed multifunctional properties, including antibacterial and antioxidative effects. In vivo experiments showed that TA-MP2 hydrogel dressings significantly accelerated wound healing in a full-layer skin wound model. These findings indicated the potential of TA-MP2 hydrogel dressings in promoting wound healing.

Phase-Engineered Robust Cocatalyst of NiFe Bicarbonate with Pt Dopant for Enhanced Photocatalytic Water Splitting.

Exploring efficient cocatalysts capable of accelerating surface catalytic reaction is of great significance for the development of solar-driven hydrogen production. Herein, on the basis of NiFe hydroxide, we developed a series of Pt doped NiFe-based cocatalysts to promote the photocatalytic hydrogen production of graphitic carbon nitride (g-C3 N4 ). We find that the Pt doping can trigger phase reconstruction of NiFe hydroxide and lead to the formation of NiFe bicarbonate, which displays higher catalytic activity toward hydrogen evolution reaction (HER). The Pt doped NiFe bicarbonate modified g-C3 N4 shows excellent photocatalytic activity with H2 evolution rate up to 100 µmol/h, which is more than 300 times that of pristine g-C3 N4 . The experimental and calculation results demonstrate that the greatly improved photocatalytic HER activity of g-C3 N4 is not only due to the efficient carrier separation, but also attributed to the accelerated HER kinetics. Our work may provide guidance for designing novel and superior photocatalysts.

Structure optimization and discovery of novel compound for the treatment of insertion mutations within exon 20 of EGFR and HER2.

In previous decades, patients with the most active EGFR mutations in non-small cell lung cancer (NSCLC) have significantly benefited from EGFR tyrosine kinase inhibitors (TKIs). However, a minority with EGFR and HER2 exon 20 mutations are inherently resistant to treatment. Several molecular TKIs (such as TAK788 and Poziotinib) were recently discovered and demonstrated as effective inhibitors against the most prevalent HER2 or EGFR exon 20 mutations. However, low clinical efficiency and uncertain adverse reaction indicated that the development of effective therapies is still demanded. In the present work, we designed several hybrid compounds learning from 3D modeling of kinase structure. One lead compound (compound 56) was found to be the most potent compound with IC50 value of 0.027 nM against EGFR D770-N771 ins NPG and reduced binding affinity with hERG protein. In vitro and in vivo biological results suggested that compound 56 demonstrated good oral bioavailability, and it was significantly capable of inhibiting the growth of tumor cells with a variety of HER2 exon 20 mutations and EGFR mutants with negligible toxic effects. It was identified that compound 56 might be considered a potential drug candidate for NSCLC target therapy.

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase-3/PARP/GSDME pathways in A549 cell line.

Cordyceps militaris (CM) is traditionally used as dietary therapy for lung cancer patients in China. CM extract (CME) is hydrosoluble fraction of CM and extensively investigated. Caspase-3-involved cell death is considered as its major anticancer mechanism but inconclusive. Therefore, we explore its caspase-3-dependent programmed cell death nature (apoptosis and pyroptosis) and validate its caspase-3-dependent property in loss-of-function experiment. Component profile of CME is detected by High Performance Liquid Chromatography- quadrupole time-of-flight mass spectrometry (HPLC-qTOF). Results show that CME causes pyroptosis-featured cell bubbling and cell lysis and inhibits cell proliferation in A549 cell. CME induces chromatin condensing and makes PI+/annexin V+ staining in bubbling cells, indicating genotoxicity, apoptosis, and pyroptosis cell death are caused by CME. High concentration of CME (200 µg/ml) exerts G2/M and G0 cell cycles arresting and suppresses P53-downstream proliferative proteins, including P53, P21, CDC25B, CyclinB1, Bcl-2, and BCL2 associated agonist of cell death (BAD), but 1-100 µg/ml of CME show less effect on proteins above. Correspondingly, caspase-3 activity and caspase-3 downstream proteins including pyroptotic effector gasdermin-E (GSDME) and apoptotic marker cleaved-poly-ADP-ribose polymerase (PARP) are significantly promoted by CME. Moreover, regarding membrane pore formation in pyroptotic cell, expression of membrane GSDME (GSDME antibody conjugated with PE-Cy7 for detection in flow cytometry) is remarkably increased by CME treatment. By contrast, other pyroptosis-related proteins such as P2X7, NLRP3, GSDMD, and Caspase-1 are not affected after CME treatment. Additionally, TET2 is unexpectedly raised by CME. In present of caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC), CME-induced cytotoxicity, cell bubbling, and genotoxicity are reduced, and CME-induced upregulation of apoptosis (cleaved-PARP-1) and pyroptosis (GSDME-NT) proteins are reversed. Lastly, 22 components are identified in HPLC-qTOF experiment, and they are classified into trophism, neoadjuvant component, cytotoxic component, and cancer deterioration promoter according to previous references. Conclusively, CME causes caspase-3-dependent apoptosis and pyroptosis in A549 through caspase-3/PARP and caspase-3/GSDME pathways, and it provides basic insight into clinic application of CME for cancer patients.

[Reduning injection inhibits replication and proliferation of mouse cytomegalovirus and down-regulates the expressions of IFN-γ and IL-6 in mouse cytomegalovirus pneumonia].

OBJECTIVE: To investigate the antiviral and immuno-regulatory effects of Reduning injection on mouse cytomegalovirus (MCMV) pneumonia. METHODS: BALB/c mice were divided randomly into five groups: blank control group, immunosuppressive control group, MCMV pneumonia group, Reduning treatment group, and ganciclovir treatment group. Acute MCMV interstitial pneumonia models were established in the latter three groups. Lung pathological changes were observed with HE staining, MCMV-DNA content in the lung tissue was detected by qRT-PCR, and the levels of interferon-γ (IFN-γ) and interleukin-6 (IL-6) in the lung tissue were determined by ELISA. RESULTS: Compared with MCMV pneumonia group, the lung injuries in Reduning treatment and ganciclovir treatment groups were ameliorated, and the MCMV-DNA expression in the two treatment groups decreased, and the changes in ganciclovir treatment group were more obvious (P < 0.05). Compared with MCMV pneumonia group, the levels of IFN-γ and IL-6 in Reduning treatment group rose by 1.4 times and dropped by 30.2%, respectively; and IFN-γ increased by 1.6 times and IL-6 decreased by 47.6% in ganciclovir treatment group (P < 0.05); the differences between the two treatment groups were statistically significant (P < 0.05). IFN-γ/IL-6 ratio in Reduning treatment group was higher than that in MCMV pneumonia group, and approached the level of immunosuppressive control group. CONCLUSION: Reduning injection might exert antiviral activity through inhibiting MCMV replication and proliferation in lung tissue directly, and down-regulating the expressions of IFN-γ and IL-6.