A nomogram-based prediction model for dysphagia in patients with chronic obstructive pulmonary disease: A cross-sectional study.

AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.

The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Onion-like multicolor thermally activated delayed fluorescent carbon quantum dots for efficient electroluminescent light-emitting diodes.

Carbon quantum dots are emerging as promising nanomaterials for next-generation displays. The elaborate structural design is crucial for achieving thermally activated delayed fluorescence, particularly for improving external quantum efficiency of electroluminescent light-emitting diodes. Here, we report the synthesis of onion-like multicolor thermally activated delayed fluorescence carbon quantum dots with quantum yields of 42.3-61.0%. Structural, spectroscopic characterization and computational studies reveal that onion-like structures assembled from monomer carbon quantum dots of different sizes account for the decreased singlet-triplet energy gap, thereby achieving efficient multicolor thermally activated delayed fluorescence. The devices exhibit maximum luminances of 3785-7550 cd m-2 and maximum external quantum efficiency of 6.0-9.9%. Importantly, owing to the weak van der Waals interactions and adequate solution processability, flexible devices with a maximum luminance of 2554 cd m-2 are realized. These findings facilitate the development of high-performance carbon quantum dots-based electroluminescent light-emitting diodes that are promising for practical applications.

The novel insights of epithelial-derived exosomes in various fibrotic diseases.

The characteristics of fibrosis include the abnormal accumulation of extracellular matrix proteins and abnormal tissue repair caused by injury, infection, and inflammation, leading to a significant increase in organ failure and mortality. Effective and precise treatments are urgently needed to halt and reverse the progression of fibrotic diseases. Exosomes are tiny vesicles derived from endosomes, spanning from 40 to 160 nanometers in diameter, which are expelled into the extracellular matrix environment by various cell types. They play a crucial role in facilitating cell-to-cell communication by transporting a variety of cargoes, including proteins, RNA, and DNA. Epithelial cells serve as the primary barrier against diverse external stimuli that precipitate fibrotic diseases. Numerous research suggests that exosomes from epithelial cells have a significant impact on several fibrotic diseases. An in-depth comprehension of the cellular and molecular mechanisms of epithelial cell-derived exosomes in fibrosis holds promise for advancing the exploration of novel diagnostic biomarkers and clinical drug targets. In this review, we expand upon the pathogenic mechanisms of epithelium-derived exosomes and highlight their role in the fibrotic process by inducing inflammation and activating fibroblasts. In addition, we are particularly interested in the bioactive molecules carried by epithelial-derived exosomes and their potential value in the diagnosis and treatment of fibrosis and delineate the clinical utility of exosomes as an emerging therapeutic modality, highlighting their potential application in addressing various medical conditions.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. METHODS: We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in-house samples. Additionally, novel therapeutic targets were identified based on these established immuno-collagenic subtypes. RESULTS: Our categorization divided tumors into three subtypes: "soft & hot" (low collagen activity and high immune infiltration), "armored & cold" (high collagen activity and low immune infiltration), and "quiescent" (low collagen activity and immune infiltration). Notably, "soft & hot" tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7-H3), an available drug target, as strongly expressed in "armored & cold" tumors, relating with poor prognosis. CONCLUSION: This study introduces histopathology-based universal immuno-collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Perspectives on Development of Optoelectronic Materials in Artificial Intelligence Age.

Optoelectronic devices, such as light-emitting diodes, have been demonstrated as one of the most demanded forthcoming display and lighting technologies because of their low cost, low power consumption, high brightness, and high contrast. The improvement of device performance relies on advances in precisely designing novelty functional materials, including light-emitting materials, hosts, hole/electron transport materials, and yet which is a time-consuming, laborious and resource-intensive task. Recently, machine learning (ML) has shown great prospects to accelerate material discovery and property enhancement. This review will summarize the workflow of ML in optoelectronic materials discovery, including data collection, feature engineering, model selection, model evaluation and model application. We highlight multiple recent applications of machine-learned potentials in various optoelectronic functional materials, ranging from semiconductor quantum dots (QDs) or perovskite QDs, organic molecules to carbon-based nanomaterials. We furthermore discuss the current challenges to fully realize the potential of ML-assisted materials design for optoelectronics applications. It is anticipated that this review will provide critical insights to inspire new exciting discoveries on ML-guided of high-performance optoelectronic devices with a combined effort from different disciplines.

Ferritin-mediated neutrophil extracellular traps formation and cytokine storm via macrophage scavenger receptor in sepsis-associated lung injury.

BACKGROUND: Sepsis is a severe systemic inflammatory disorder manifested by a dysregulated immune response to infection and multi-organ failure. Numerous studies have shown that elevated ferritin levels exist as an essential feature during sepsis and are able to suggest patients' prognoses. At the same time, the specific mechanism of ferritin-induced inflammatory injury remains unclear. METHODS: Hyper-ferritin state during inflammation was performed by injecting ferritin into a mouse model and demonstrated that injection of ferritin could induce a systemic inflammatory response and increase neutrophil extracellular trap (NET) formation.Padi4-/-, Elane-/- and Cybb-/- mice were used for the NETs formation experiment. Western blot, immunofluorescence, ELISA, and flow cytometry examined the changes in NETs, inflammation, and related signaling pathways. RESULTS: Ferritin induces NET formation in a peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), and reactive oxygen species (ROS)-dependent manner, thereby exacerbating the inflammatory response. Mechanistically, ferritin induces the expression of neutrophil macrophage scavenger receptor (MSR), which promotes the formation of NETs. Clinically, high levels of ferritin in patients with severe sepsis correlate with NETs-mediated cytokines storm and are proportional to the severity of sepsis-induced lung injury. CONCLUSIONS: In conclusion, we demonstrated that hyper-ferritin can induce systemic inflammation and increase NET formation in an MSR-dependent manner. This process relies on PAD4, NE, and ROS, further aggravating acute lung injury. In the clinic, high serum ferritin levels are associated with elevated NETs and worse lung injury, which suggests a poor prognosis for patients with sepsis. Our study indicated that targeting NETs or MSR could be a potential treatment to alleviate lung damage and systemic inflammation during sepsis. Video Abstract.

Risk factors of postoperative delirium following spine surgery: A meta-analysis of 50 cohort studies with 1.1 million participants.

Objectives: Postoperative delirium (POD) is considered to be a common complication of spine surgery. Although many studies have reported the risk factors associated with POD, the results remain unclear. Therefore, we performed a meta-analysis to identify risk factors for POD among patients following spinal surgery. Methods: We systematically searched the PubMed, Embase and the Cochrane Library for relevant articles published from 2006 to February 1, 2023 that reported risk factors associated with the incidence of POD among patients undergoing spinal surgery. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed, and random effects models were used to estimate pooled odds ratio (OR) estimates with 95 % confidence intervals (CIs) for each factor. The evidence from observational studies was classified according to Egger's P value, total sample size, and heterogeneity between studies. Results: Of 11,329 citations screened, 50 cohort studies involving 1,182,719 participants met the inclusion criteria. High-quality evidence indicated that POD was associated with hypertension, diabetes mellitus, cardiovascular disease, pulmonary disease, older age (>65 years), patients experiencing substance use disorder (take drug ≥1 month), cerebrovascular disease, kidney disease, neurological disorder, parkinsonism, cervical surgery, surgical site infection, postoperative fever, postoperative urinary tract infection, and admission to the intensive care unit (ICU). Moderate-quality evidence indicated that POD was associated with depression, American Society of Anesthesiologists (ASA) fitness grade (>II), blood transfusion, abnormal potassium, electrolyte disorder, length of stay, inability to ambulate and intravenous fluid volume. Conclusions: Conspicuous risk factors for POD were mainly patient- and surgery-related. These findings help clinicians identify high-risk patients with POD following spinal surgery and recognize the importance of early intervention.

Thiophenpiperazine amide derivatives as new dual MOR and σ1R ligands for the treatment of pain.

A new series of thiophenpiperazine amide derivatives as potent dual ligands for the µ-opioid (MOR) and sigma-1 (σ1R) receptors are reported. Compound 23 exhibited good affinity to σ1R (Ki = 44.7 ± 7.05 nM) and high selectivity to σ2R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED50 = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED50 = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ1R antagonism.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

Altered metabolism in right basal ganglia associated with asymptomatic neurocognitive impairment in HIV-infected individuals.

Background: Only few studies have focused on the metabolite differences between asymptomatic neurocognitive impairment (ANI) and cognitively normal people living with HIV (PLWH). The current study aims to examine whether brain metabolisms in basal ganglia (BG) by magnetic resonance spectroscopy (MRS) were potential to discriminate ANI from cognitively normal PLWH. Methods: According to neuropsychological (NP) test, 80 PLWH (37.4 ± 10.2 years) were divided into ANI group (HIV-ANI, n = 31) and NP normal group (HIV-normal, n = 49). Brain metabolisms by MRS from right BG were compared between groups, including N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), and choline-containing compounds (tCho). A total value of three metabolites were introduced. All brain metabolisms were evaluated as its percentage of total. Furthermore, correlations between MRS and NP and clinical measures were evaluated. A logistic regression model was applied, and the AUC values for the model and the continuous factors were compared using receiver operating curve (ROC) analysis. Results: Compared to HIV-normal group, tNAA/total was lower and tCr/total was higher in the HIV-ANI group (P < 0.05). Both tNAA/total and tCr/total values were correlated with NP score (P < 0.05), especially in verbal fluency, speed of information processing, learning, and recall (P < 0.05). The logistic model included BG-tCr/total, current CD4 and infection years of PLWH. The AUC value for the BG-tCr/total was 0.696 and was not significantly lower than that for logistic model (P < 0.01). Conclusion: The altered brain metabolites in the right BG were found in the ANI group compared to PLWH with normal cognition, and further associated with NP deficits. The current findings indicated that brain metabolites assessed by MRS has the potential to discriminate ANI from cognitively normal PLWH.

A Central Auditory Test reveals differences between drug treatment regimens in adults living with HIV.

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.

Lipophilic AIEgens as the "Trojan Horse" with Discrepant Efficacy in Tracking and Treatment of Mycobacterial Infection.

The highly contagious tuberculosis is a leading infectious killer, which urgently requires effective diagnosis and treatment methods. To address these issues, three lipophilic aggregation-induced emission (AIE) photosensitizers (TTMN, TTTMN, and MeOTTMN) are selected to evaluate their labeling and antimicrobial properties in vitro and in vivo. These three lipophilic AIEgens preserve low cytotoxicity and achieve real-time and non-invasive visualization of the process of mycobacteria infection in vitro and in vivo. More importantly, these AIEgens can be triggered by white light to produce reactive oxygen species (ROS), which is a highly efficient antibacterial reagent. Among these AIEgens, the TTMN photosensitizer has an outstanding antibacterial efficacy over the clinical first-line drug rifampicin at the same therapeutic concentration. Interestingly, this study also finds that TTMN can increase the expression of pro-inflammatory cytokines in the early stage of infection after light irradiation, indicating an additional pro-inflammatory role of TTMN. This work provides some feasibility basis for developing AIEgens-based agents for effectively destroying mycobacterium.

Recent Progress in 2D Metal-Organic Framework-Related Materials.

2D metal-organic frameworks-based (2D MOF-related) materials benefit from variable topological structures, plentiful open active sites, and high specific surface areas, demonstrating promising applications in gas storage, adsorption and separation, energy conversion, and other domains. In recent years, researchers have innovatively designed multiple strategies to avoid the adverse effects of conventional methods on the synthesis of high-quality 2D MOFs. This review focuses on the latest advances in creative synthesis techniques for 2D MOF-related materials from both the top-down and bottom-up perspectives. Subsequently, the strategies are categorized and summarized for synthesizing 2D MOF-related composites and their derivatives. Finally, the current challenges are highlighted faced by 2D MOF-related materials and some targeted recommendations are put forward to inspire researchers to investigate more effective synthesis methods.

The impact of perioperative opioid use on postoperative outcomes following spinal surgery: a meta-analysis of 60 cohort studies with 13 million participants.

BACKGROUND CONTEXT: An important factor for the prognosis of spinal surgery is the perioperative use of opioids. However, the relationship is not clear. PURPOSE: The purpose of this study was to evaluate the effect of perioperative opioid use on the prognosis of patients following spinal surgery. STUDY DESIGN/SETTING: Systematic review and meta-analysis. OUTCOME MEASURES: A meta-analysis was conducted using the random-effects method to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched to find relevant articles that were published until September 2, 2022. The primary outcome was prolonged postoperative opioid use, and secondary outcomes included the length of stay (LOS), reoperation, the time to return to work (RTW), postoperative complications, gastrointestinal complications, new permanent disability, central nervous system events and infection. In addition, subgroup analysis of the primary outcome was conducted to explore the main sources of heterogeneity, and sensitivity analysis of all outcomes was performed to evaluate the stability of the results. RESULTS: A total of 60 cohort studies involving 13,219,228 individuals met the inclusion criteria. Meta-analysis showed that perioperative opioid use was specifically related to prolonged postoperative opioid use (OR 6.91, 95% CI 6.09 to 7.84, p<.01). Furthermore, the results also showed that perioperative opioid use was significantly associated with prolonged LOS (OR 1.74, 95% CI 1.39 to 2.18, p<.01), postoperative complications (OR 1.72, 95% CI 1.26 to 2.36, p<.01), reoperation (OR 2.38, 95% CI 1.85 to 3.07, p<.01), the time to RTW (OR 0.45, 95% CI 0.39 to 0.52, p<.01), gastrointestinal complications (OR 1.39, 95% CI 1.30 to 1.48, p<.01), central nervous system events (OR 1.99, 95% CI 1.21 to 3.27, p=.07) and infection (OR 1.22, 95% CI 1.09 to 1.36, p=.01). These results were corroborated by the trim-and-fill procedure and leave-one-out sensitivity analyses. CONCLUSIONS: Based on the current evidence, patients with perioperative opioid use, in comparison to controls, appear to have prolonged postoperative opioid use, which may increase the risk of poor outcomes including prolonged LOS, complications, reoperation, RTW and so on. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous. These findings may help clinicians to realize the harmfulness of perioperative use of opioids, reduce the use of prescription opioids, necessarily withdraw before operation or significantly wean to the lowest tolerable preoperative amount, and provide some inspiration for standardizing the use of opioids in the future.

The emergence and prospects of carbon dots with solid-state photoluminescence for light-emitting diodes.

The significant features of carbon dots (CDs), such as bright and tunable photoluminescence, high thermal stability, and low toxicity, endow them with tremendous potential for application in next generation optoelectronics. Despite great progress achieved in the design of high-performance CDs so far, the practical applications in solid-state lighting and displays have been retarded by the aggregation-caused quenching (ACQ) effect ascribed to direct π-π interactions. This review provides a comprehensive overview of the recent progress made in solid-state CD emitters, including their synthesis, optical properties and applications in light-emitting diodes (LEDs). Their triplet-excited-state-involved properties, as well as their recent advances in phosphor-converted LEDs and electroluminescent LEDs, are mainly reviewed here. Finally, the prospects and challenges of solid-state CD-based LEDs are discussed with an eye on future development. We hope that this review will provide critical insights to inspire new exciting discoveries on solid-state CDs from both fundamental and practical standpoints so that the realization of their potential in optoelectronic areas can be facilitated.

miR-21 Expressed by Dermal Fibroblasts Enhances Skin Wound Healing Through the Regulation of Inflammatory Cytokine Expression.

The management of skin wound healing is still a challenge. MicroRNA-21 (miR-21) has been reported to play important roles in wound repair; however, the underlying mechanism needs to be further clarified. The present study aimed to study the direct role of miR-21 in skin wound healing in miR-21 KO mice and to investigate the role of miR-21 in controlling the migration and proliferation of primary human skin cells and its underlying mechanism(s). miR-21 KO and wild-type (WT) mice were used for in vivo wound healing assays, while mouse and human primary skin cells were used for in vitro assays. miR-21 inhibitors or mimics or negative control small RNAs were transfected to either inhibit or enhance miR-21 expression in the human primary dermal fibroblasts or epidermal cells. RNA sequencing analysis was performed to identify the potential molecular pathways involved. We found that the loss of miR-21 resulted in slower wound healing in miR-21 KO mouse skin and especially delayed the healing of dermal tissue. In vitro assays demonstrated that the reduced expression of miR-21 caused by its inhibitor inhibited the migration of human primary dermal fibroblasts, which could be enhanced by increased miR-21 expression caused by miR-21 mimics. RNA-sequence analysis revealed that the inhibition of miR-21 expression downregulated the inflammatory response pathways associated with the decreased expression of inflammatory cytokines, and the addition of IL-1ß into the culture medium enhanced the migration and proliferation of dermal fibroblasts in vitro. In conclusion, miR-21 in dermal fibroblasts can promote the migration and growth of epidermal and dermal cells to enhance skin wound healing through controlling the expression of inflammatory cytokines.

Development and validation of a deep learning model for multicategory pneumonia classification on chest computed tomography: a multicenter and multireader study.

Background: Accurate diagnosis of pneumonia is vital for effective disease management and mortality reduction, but it can be easily confused with other conditions on chest computed tomography (CT) due to an overlap in imaging features. We aimed to develop and validate a deep learning (DL) model based on chest CT for accurate classification of viral pneumonia (VP), bacterial pneumonia (BP), fungal pneumonia (FP), pulmonary tuberculosis (PTB), and no pneumonia (NP) conditions. Methods: In total, 1,776 cases from five hospitals in different regions were retrospectively collected from September 2019 to June 2023. All cases were enrolled according to inclusion and exclusion criteria, and ultimately 1,611 cases were used to develop the DL model with 5-fold cross-validation, with 165 cases being used as the external test set. Five radiologists blindly reviewed the images from the internal and external test sets first without and then with DL model assistance. Precision, recall, F1-score, weighted F1-average, and area under the curve (AUC) were used to evaluate the model performance. Results: The F1-scores of the DL model on the internal and external test sets were, respectively, 0.947 [95% confidence interval (CI): 0.936-0.958] and 0.933 (95% CI: 0.916-0.950) for VP, 0.511 (95% CI: 0.487-0.536) and 0.591 (95% CI: 0.557-0.624) for BP, 0.842 (95% CI: 0.824-0.860) and 0.848 (95% CI: 0.824-0.873) for FP, 0.843 (95% CI: 0.826-0.861) and 0.795 (95% CI: 0.767-0.822) for PTB, and 0.975 (95% CI: 0.968-0.983) and 0.976 (95% CI: 0.965-0.986) for NP, with a weighted F1-average of 0.883 (95% CI: 0.867-0.898) and 0.846 (95% CI: 0.822-0.871), respectively. The model performed well and showed comparable performance in both the internal and external test sets. The F1-score of the DL model was higher than that of radiologists, and with DL model assistance, radiologists achieved a higher F1-score. On the external test set, the F1-score of the DL model (F1-score 0.848; 95% CI: 0.824-0.873) was higher than that of the radiologists (F1-score 0.541; 95% CI: 0.507-0.575) as was its precision for the other three pneumonia conditions (all P values <0.001). With DL model assistance, the F1-score for FP (F1-score 0.541; 95% CI: 0.507-0.575) was higher than that achieved without assistance (F1-score 0.778; 95% CI: 0.750-0.807) as was its precision for the other three pneumonia conditions (all P values <0.001). Conclusions: The DL approach can effectively classify pneumonia and can help improve radiologists' performance, supporting the full integration of DL results into the routine workflow of clinicians.

Surface Hydrogen Bond-Induced Oxygen Vacancies of TiO2 for Two-Electron Molecular Oxygen Activation and Efficient NO Oxidation.

Defect engineering can provide a feasible approach to achieving ambient molecular oxygen activation. However, conventional surface defects (e.g., oxygen vacancies, OVs), featured with the coordinatively unsaturated metal sites, often favor the reduction of O2 to •O2- rather than O22- via two-electron transfer, hindering the efficient pollutant removal with high electron utilization. Herein, we demonstrate that this bottleneck can be well discharged by modulating the electronic structure of OVs via phosphorization. As a proof of concept, TiO2 nanoparticles are adopted as a model material for NaH2PO2 (HP) modification, in which HP induces the formation of OVs via weakening the Ti-O bonds through the hydrogen bond interactions. Additionally, the formed Ti-O-P covalent bond refines the electronic structure of OVs, which enables rapid electron transfer for two-electron molecular oxygen activation. As exemplified by NO oxidation, HP-modified TiO2 with abundant OVs achieved complete NO removal with high selectivity for benign nitrate, superior to that of pristine TiO2. This study highlights a promising approach to regulate the O2 activation via an electronic structure modulation and provides fresh insights into the rational design of a photocatalyst for environmental remediation.

METTL3-mediated N6-methyladenosine exacerbates ferroptosis via m6A-IGF2BP2-dependent mitochondrial metabolic reprogramming in sepsis-induced acute lung injury.

Neutrophil extracellular traps (NETs), released by polymorphonuclear neutrophils (PMNs), exert a robust antimicrobial function in infectious diseases such as sepsis. NETs also contribute to the pathogenesis and exacerbation of sepsis. Although the lung is highly vulnerable to infections, few studies have explored the role of NETs in sepsis-induced acute lung injury (SI-ALI). We demonstrate that NETs induce SI-ALI via enhanced ferroptosis in alveolar epithelial cells. Our findings reveal that the excessive release of NETs in patients and mice with SI-ALI is accompanied by upregulation of ferroptosis depending on METTL3-induced m6A modification of hypoxia-inducible factor-1α (HIF-1α) and subsequent mitochondrial metabolic reprogramming. In addition to conducting METTL3 overexpression and knockdown experiments in vitro, we also investigated the impact of ferroptosis on SI-ALI caused by NETs in a caecum ligation and puncture (CLP)-induced SI-ALI model using METTL3 condition knockout (CKO) mice and wild-type mice. Our results indicate the crucial role of NETs in the progression of SI-ALI via NET-activated METTL3 m6A-IGF2BP2-dependent m6A modification of HIF-1α, which further contributes to metabolic reprogramming and ferroptosis in alveolar epithelial cells.