Quaternization of a Triphenylamine-Based Conjugated Porous Organic Polymer to Immobilize PtCl62- for the Photocatalytic Reduction of 4-Nitrophenol.

Photocatalytic reduction of 4-nitrophenol (4-NP) for converting it to nontoxic 4-aminophenol (4-AP) is one of the most efficient approaches for removing toxic 4-NP. Using porous organic polymers (POPs) as the support to immobilize noble metal catalysts has exhibited remarkable reduction performance but is rarely reported. Herein, a cationic triphenylamine-based POP was synthesized by quaternization to immobilize PtCl62- to prepare an efficient photocatalyst named DCM-TPA-Pt for the reduction of 4-NP to 4-AP in the presence of NaBH4. Different from reported methods which realize immobilization by doping or complexing, the support and PtCl62- are combined through electrostatic interaction with milder reaction conditions to produce a photocatalyst in this work. DCM-TPA-Pt shows excellent photocatalytic reduction performance, reaching 99.9% conversion within 3 min, and its pseudo-first-order constant is 0.0305 s-1, surpassing most of the reported photocatalysts. Moreover, DCM-TPA-Pt also exhibits equal reduction efficiency after five continuous cycles, which highlights its potential utilization in practical applications.

A near-infrared-II light-response BODIPY-based conjugated microporous polymer for enhanced photocatalytic degradation of cationic dyes and H2O2 production.

A BODIPY-containing conjugated microporous polymer (CMP, LBFD-1) was modified with calixarene to develop a hydrophilic CMP (LBFD-2) with broader absorption extending to the near-infrared-II region. LBFD-2 exhibited an H2O2 production rate of 2.14 mmol g-1 h-1 in the air without any sacrificial agents. The removal efficiency (η) of LBFD-2 towards methylene blue and rhodamine B reached >99.5% within 20 and 40 min in light. LBFD-2 can withstand diverse environmental changes, showing excellent reusability and potential for practical applications in real-water systems.

Genome-wide identification and expression analysis of the CONSTANS-like family in potato (Solanum tuberosum L.).

The CONSTANS-like (COL) gene plays important roles in plant growth, development, and abiotic stress. A total of 15 COL genes are unevenly distributed on eight chromosomes in the potato genome. The amino acid length of the family members was 347-453 aa, the molecular weight was 38.65-49.92 kD, and the isoelectric point was 5.13-6.09. The StCOL family can be divided into three subfamilies by evolutionary tree analysis, with conserved motifs and similar gene structure positions in each subfamily. The analysis of promoter cis-acting elements showed 17 cis-acting elements related to plant hormones, stress, and light response. Collinearity analysis of COL genes of tomato, potato, and Arabidopsis showed that 13 StCOL genes in the different species may have a common ancestor. A total of 10 conserved motifs and six kinds of post-translational modifications in the 15 StCOL proteins were identified. The 15 StCOL genes exhibit a genomic structure consisting of exons and introns, typically ranging from two to four in number. The results showed that 10 genes displayed significant expression across all potato tissues, while the remaining five genes were down-expressed in potato transcriptome data. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis exhibited differential expression of 8 StCOL genes in the potato leaves and tubers at different growth stages, as well as 7 StCOL genes under 2°C treatment conditions. These results suggested that the StCOL gene family may play an important role in regulating potato tuberization and responding to cold stress.

Prediction of the short-term efficacy and recurrence of photodynamic therapy in the treatment of oral leukoplakia based on deep learning.

BACKGROUND: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. METHODS: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. RESULTS: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. CONCLUSIONS: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.

Construction of Prediction Model of Foodborne Disease Outbreaks and Its Trend Prediction - Guizhou Province, China, 2023-2025.

Objective: Foodborne diseases pose a significant public health concern globally. This study aims to analyze the correlation between disease prevalence and climatic conditions, forecast the pattern of foodborne disease outbreaks, and offer insights for effective prevention and control strategies and optimizing health resource allocation policies in Guizhou Province. Methods: This study utilized the χ2 test and four comprehensive prediction models to analyze foodborne disease outbreaks recorded in the Guizhou Foodborne Disease Outbreak system between 2012 and 2022. The best-performing model was chosen to forecast the trend of foodborne disease outbreaks in Guizhou Province, 2023-2025. Results: Significant variations were observed in the incidence of foodborne disease outbreaks in Guizhou Province concerning various meteorological factors (all P≤0.05). Among all models, the SARIMA-ARIMAX combined model demonstrated the most accurate predictive performance (RMSE: Prophet model=67.645, SARIMA model=3.953, ARIMAX model=26.544, SARIMA-ARIMAX model=26.196; MAPE: Prophet model=42.357%, SARIMA model=37.740%, ARIMAX model=15.289%, SARIMA-ARIMAX model=13.961%). Conclusion: The analysis indicates that foodborne disease outbreaks in Guizhou Province demonstrate distinct seasonal patterns. It is recommended to concentrate prevention efforts during peak periods. The SARIMA-ARIMAX hybrid model enhances the precision of monthly forecasts for foodborne disease outbreaks, offering valuable insights for future prevention and control strategies.

Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC. Methods: By utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan-Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines in vitro. Results: As a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population.

Oral epithelial dysplasia detection and grading in oral leukoplakia using deep learning.

BACKGROUND: The grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia. METHODS: Four convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model. RESULTS: EfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4-90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4-90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843). CONCLUSIONS: E-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice.

Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway.

Tumor immune evasion is a hallmark of Head and Neck Cancers. The advent of immune checkpoint inhibitors (ICIs) in the first-line setting has transformed the management of these tumors. Unfortunately, the response rate of Head and Neck Squamous Cell Carcinomas (HNSCC) to ICIs is below 15%, regardless of the human papillomavirus (HPV) status, which might be partially related with impaired antigen presentation machinery (APM). Mechanistically, HNSCC cells are usually defective in the expression of MHC-I associated APM, while this transcriptional pathway is critical for the activation of tumor-killing effector T-cells. To specifically illuminate the phenomenon and seek for therapeutic strategies, this review summarizes the most recently identified role of genetic and functional dysregulation of the MHC-I pathway, specifically through changes at the genetic, epigenetic, post-transcriptional, and post-translational levels, which substantially contributes to HNSCC immune escape and ICI resistance. Several treatment modalities can be potentially exploited to restore APM signaling in tumors, which improves anti-tumor immunity through the activation of interferons, vaccines or rimantadine against HPV and the inhibition of EGFR, SHP-2, PI3K and MEK. Additionally, the combinatorial use of radiotherapy or cytotoxic agents with ICIs can synergize to potentiate APM signaling. Future directions would include further dissection of MHC-I related APM signaling in HNSCC and whether reversing this inhibition in combination with ICIs would elicit a more robust immune response leading to improved response rates in HNSCC. Therapeutic approaches to restore the MHC-I antigen presentation machinery in Head and Neck Cancer. (Red color texts represent the according strategies and the outcomes).

Feedback Intervention for the Control of Glucocorticoid Prescription in Primary Care Institutions: A Cluster Randomized Cross-Over Controlled Trial in Southwest China.

Purpose: The purpose of this study is to assess the effect of glucocorticoid prescription feedback intervention in complex primary care institutions for regulating its inappropriate use. Design Setting and Interventions: A six-month cluster randomized cross-over controlled trial was conducted in primary care institutions. A total of 347 physicians from 69 participating institutions were randomly allocated to either group A or group B. Both groups were given feedback interventions or serve as control. The feedback intervention comprised two components: a real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and a high-proportion prescription feedback intervention warning system. Outcome Measures: The primary outcome measure was the 10-day inappropriate glucocorticoid prescription rate, while the 10-day glucocorticoid prescription rate served as secondary outcome measure. Results: At baseline, the 10-day inappropriate glucocorticoid prescription rates were 66.63% and 66.57% in group A and group B, respectively, showing no significant difference (p = 0.140). Following the intervention, group A exhibited a significant reduction in 10-day inappropriate glucocorticoid prescription rate at the crossing point by 13.69% (p < 0.001). In contrast, group B, which served as the control group, experienced an increase of 5.93% (p = 0.037) at the same crossover point. After the crossover point, there was a decrease in 10-day inappropriate glucocorticoid prescription rate for both groups. Group B as the intervention group demonstrated a reduction of 28.22% compared to the crossing point (p < 0.001), whereas group A showed a decrease of 12.20% (p = 0.339). The characteristics of physicians did not significantly influence the inappropriate glucocorticoid prescription rate. Conclusion: The real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and high-proportion prescription feedback intervention warning system can effectively regulate the inappropriate glucocorticoid prescribing behavior of physicians. Trial Registration: ISRCTN11747547.

Trends and Patterns of Systemic Glucocorticoid Prescription in Primary Care Institutions in Southwest China, from 2018 to 2021.

Purpose: The purpose of this study was to investigate the prescribing patterns and usage trends of systemic glucocorticoids in primary care institutions located in Southwest China from 2018 to 2021. Materials and Methods: A retrospective cross-sectional analysis of systemic glucocorticoids prescriptions was conducted in 32 primary care institutions located in Southwest China between 2018 and 2021. Prescriptions of systemic glucocorticoids were classified as appropriate or inappropriate use. Inappropriate use was further classified into (1) inappropriate indications and (2) inappropriate selection of glucocorticoids. Generalized estimation equations were employed to investigate the factors associated with inappropriate utilization of systemic glucocorticoids. The seasonal autoregressive integrated moving average (SARIMA) model was employed to predict the rate of inappropriate glucocorticoids prescriptions. Results: A total of 203,846 (92.89%) prescriptions were included, both the number of systemic glucocorticoids prescriptions and inappropriate prescriptions increased in winter. Diseases of the respiratory system (68.90%) were the most frequent targets of systemic glucocorticoids use. Of all prescriptions, 73.18% exhibited inappropriate indications, while 0.05% demonstrated inappropriate selection. The utilization of systemic glucocorticoids was deemed inappropriate for diseases of the respiratory system (94.19%), followed by diseases of the digestive system (87.75%). Physicians, who were female or younger than 33 years old, possess lower levels of education and professional titles and exhibit a higher likelihood of inappropriately prescribing systemic glucocorticoids. The phenomenon of inappropriate glucocorticoids use was commoner among male patients aged 65 years and older. After conducting model verification, it was determined that the SARIMA model could be used to predict the monthly rate of inappropriate systemic glucocorticoids prescriptions in primary care institutions in southwest China. Conclusion: The inappropriate use of systemic glucocorticoids remains a significant concern in primary care institutions. In this regard, continuing education and professional knowledge training of physicians should be strengthened in the future.

Multiple myeloma initially manifesting as a solitary deep ulcer on the tongue: a case study and literature review.

Multiple myeloma (MM) is a malignant disease associated with clonal plasma cell proliferative disorder, characterized by extensive infiltration of clonal plasma cells in the bone marrow, for which a proportion of patients suffer poor outcome and exhibit no obvious symptoms in the early stages. Amyloidosis is a rare condition caused by MM. Immunoglobulin light chain amyloidosis (AL) is caused by the secretion of specific toxic light chain proteins from proliferating clonal B cells or plasma cells. These light chain proteins accumulate in human tissues and cause organ dysfunction and failure. Oral manifestations of amyloidosis include macroglossia, prominent lingual margins, coloured papules, purpura, and nodular protrusions. To describe and summarize the oral manifestations associated with AL amyloidosis in order to achieve an accurate clinical diagnosis. We present a case of AL amyloidosis associated with multiple myeloma and review the literature on other related cases identified from the inception of Medline. A female patient visited our clinic with a deep tongue ulcer. After oral biopsy and tissue staining, combined with the examination results from the Department of Haematology, the patient was diagnosed with oral AL amyloidosis related to multiple myeloma. This is the first case study of AL amyloidosis secondary to latent MM presenting as a solitary tongue ulcer. Chronic oral refractory ulcers may be associated with systemic diseases and should be considered in future clinical practice.

Developing Single-Atomic Manganese Nanozymes for Synergistic Mild Photothermal/Multienzymatic Therapy.

Synergistic mild photothermal/nanozyme therapy with outstanding hyperthermia performance and excellent multienzyme properties is highly needed for osteosarcoma treatment. Herein, we have developed efficient single-atom nanozymes (SANs) consisting of Mn sites atomically dispersed on nitrogen-doped carbon nanosheets (denoted as Mn-SANs) for synergistic mild photothermal/multienzymatic therapy against osteosarcoma. Benefiting from their black N-doped carbon nanosheet matrices, Mn-SANs showed an excellent NIR-II-triggered photothermal effect. On the other hand, Mn-SANs with atomically dispersed Mn sites have outstanding multienzyme activities. Mn-SANs can catalyze endogenous H2O2 in osteosarcoma into O2 by catalase (CAT)-like activity, which can effectively ease osteosarcoma hypoxia and trigger the oxidase (OXD)-like catalysis that converts O2 to the cytotoxic superoxide anion radical (•O2-). At the same time, Mn-SANs can also mimic glutathione oxidase (GSHOx) to effectively consume the antioxidant glutathione (GSH) in osteosarcoma and inhibit intracellular glutathione peroxidase 4 (GPX4) expression. Such intratumoral •O2- production, GSH depletion, and GPX4 inactivation mediated by Mn-SANs can create a large accumulation of lipid peroxides (LPO) and •O2-, leading to oxidative stress and disrupting the redox homeostasis in osteosarcoma cells, which can ultimately induce osteosarcoma cell death. More importantly, heat shock proteins (HSPs) can be significantly destroyed via Mn-SAN-mediated plentiful LPO and •O2- generation, thus effectively impairing osteosarcoma cells resistant to mild photothermal therapy. Overall, through the cooperative effect of chemical processes (boosting •O2-, consuming GSH, and enhancing LPO) and biological processes (inactivating GPX4 and hindering HSPs), collaborative mild photothermal/multienzymatic therapy mediated by Mn-SANs is a promising strategy for efficient osteosarcoma treatment.