Olink Proteomics-Based Exploration of Immuno-Oncology-Related Biomarkers Leading to Lung Adenocarcinoma Progression.

INTRODUCTION: It is crucial to investigate the distinct proteins that contribute to the advancement of lung cancer. MATERIAL AND METHODS: We analyzed the expression levels of 92 immuno-oncology-related proteins in 96 pairs of lung adenocarcinoma tissue samples using Olink proteomics. The differentially expressed proteins (DEPs) were successively screened in tumor and paraneoplastic groups, early and intermediate-late groups by a nonparametric rank sum test, and the distribution and expression levels of DEPs were determined by volcano and heat maps, etc., and the area under the curve was calculated. RESULTS: A total of 24 DEPs were identified in comparisons between tumor and paracancerous tissues. Among them, interleukin-8 (IL8) and chemokine (C-C motif) ligand 20 (CCL20) as potential markers for distinguishing tumor tissues. Through further screening, it was found that interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) may be able to lead to tumor progression through the JaK-STAT signaling pathway, Toll-like receptor signaling pathway and PI3K/AKT signaling pathway. Interestingly, our study revealed a down-regulation of IL6 and VEGFA in tumor tissues compared to paracancerous tissues. CONCLUSIONS: IL8 + CCL20 (AUC: 0.7056) have the potential to differentiate tumor tissue from paracancerous tissue; IL6 + VEGFA (AUC: 0.7531) are important protein markers potentially responsible for tumor progression.

Ru(II)-Ru(II) and Ru(II)-Os(II) Homo-/Heterodinuclear Complexes and Ru3(II)-Ru(II) Homotetranuclear Complexes Based on Heteroditopic Bridging Ligands: Synthesis, Photophysics, and Effective Energy Transfer.

In this paper, the synthesis, photophysics, electrochemistry, and intramolecular energy transfer of two series of dinuclear and tetranuclear metallic complexes [(bpy)2M1LxM2(bpy)2]4+ (x = 1, 2; M1 = Ru, M2 = Ru/Os; M1 = Os, M2 = Ru) and {[Ru(bpy)2(Lx)]3Ru}8+ based on new heteroditopic bridging ligands (L1 = 6-phenyl-4-Hpip-2-2'-bipyridine, L2 = 6-Hpip-2-2'-bipyridine, Hpip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) are reported. The dimetallic and tetrametallic complexes exhibit rich redox properties with successive reversible metal-centered oxidation and ligand-centered reduction couples. All complexes display intense absorption in the entire ultraviolet-visible spectral regions. The mononuclear [LxRu(bpy)2]2+ and homodinuclear [(bpy)2RuLxRu(bpy)2]4+ complexes display strong Ru-based characteristic emission at room temperature. Interestingly, the optical studies of heterodinuclear complexes reveal almost complete quenching of the RuII-based emission and efficient photoinduced energy transfer, resulting in an OsII-based emission in the near-infrared region. As a result of the intramolecular energy transfer from the center to the periphery and steric hindrance quenching of the peripheral RuII-centered emissive triplet metal-to-ligand charge transfer states, the tetranuclear complexes exhibit weak RuII-based emission with a short lifetime. Since the light absorbed by several chromophores is efficiently directed to the subunit with the lowest-energy excited state, the present multinuclear complexes can be used as well-visible-light-absorption antennas.

The ATF4-regulated LncRNA MALAT1 promotes odontoblastic differentiation of human dental pulp stem cells via histone demethylase JMJD3: An in vitro study.

AIM: This study aimed to investigate the upstream regulators and specific mechanisms of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). METHODOLOGY: Human dental pulp stem cells were isolated and cultured, followed by conducting loss- or gain-of-function experiments on ATF4 and loss experiments on MALAT1 to elucidate their respective biological functions in odontoblastic differentiation. Chromatin immunoprecipitation assays and RNA immunoprecipitation were performed to uncover the interaction between ATF4-MALAT1 and MALAT1-JMJD3, respectively. The odontoblastic differentiation was estimated by the mRNA and protein of DSPP and DMP1, as well as alkaline phosphatase staining. RESULTS: Expression of MALAT1 was upregulated in the hDPSCs cultured in an odontoblastic medium, and MALAT1 downregulation suppressed the odontoblastic differentiation of the hDPSCs. Subsequent experiments confirmed that ATF4 promoted odontoblastic differentiation and induced MALAT1 expression by binding to the MALAT1 promoter region. Further experiments revealed that nuclear MALAT1 interacted with JMJD3. MALAT1 knockdown decreased the JMJD3 protein level and demethylase activity, and it enhanced H3K27me3 occupancy of the promoter region of DSPP and DMP1, resulting in the inhibition of DSPP and DMP1 transcription. Importantly, JMJD3 overexpression significantly attenuated the inhibition of odontoblastic differentiation induced by MALAT1 knockdown. CONCLUSIONS: ATF4-regulated MALAT1 plays a positive regulatory role in odontoblastic differentiation of hDPSCs through JMJD3-mediated H3K27me3 modifications of the DSPP and DMP1 promoters.

Non-Radical Activation of Peracetic Acid by Powdered Activated Carbon for the Degradation of Sulfamethoxazole.

Environmental-friendly and low-cost catalysts for peracetic acid (PAA) activation are vital to promote their application for micropollutant degradation in water. In this study, powdered activated carbon (PAC) was reported to improve the degradation of sulfamethoxazole (SMX). The improvement of SMX degradation in the PAC/PAA system was expected to be because of the PAA activation rather than the co-existing H2O2 activation. Non-radical oxidation pathways, including the mediated electron-transfer process and singlet oxygen (1O2), were evidenced to play the dominant roles in the degradation of micro-organic pollutants. The graphitization of PAC, persistent free radicals, and electron-donating groups like C-OH were proposed to contribute to the activation of PAA. High SMX degradation could be achieved in the acidic and neutral conditions in the PAC/PAA system. Overall, higher dosages of PAC (0-0.02 g/L) and PAA (0-100 µM) benefited the degradation of SMX. The presence of HCO3- could lower the SMX degradation significantly, while Cl-, PO43-, and humic acid (HA) only reduced the SMX degradation efficiency a little. Overall, this study offered an efficient non-radical PAA activation method using PAC, which can be effectively used to degrade micro-organic pollutants.

The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents.

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.

Cluster features in fibrosing interstitial lung disease and associations with prognosis.

BACKGROUND: Clustering is helpful in identifying subtypes in complex fibrosing interstitial lung disease (F-ILD) and associating them with prognosis at an early stage of the disease to improve treatment management. We aimed to identify associations between clinical characteristics and outcomes in patients with F-ILD. METHODS: Retrospectively, 575 out of 926 patients with F-ILD were eligible for analysis. Four clusters were identified based on baseline data using cluster analysis. The clinical characteristics and outcomes were compared among the groups. RESULTS: Cluster 1 was characterized by a high prevalence of comorbidities and hypoxemia at rest, with the worst lung function at baseline; Cluster 2 by young female patients with less or no smoking history; Cluster 3 by male patients with highest smoking history, the most noticeable signs of velcro crackles and clubbing of fingers, and the severe lung involvement on chest image; Cluster 4 by male patients with a high percentage of occupational or environmental exposure. Clusters 1 (median overall survival [OS] = 7.0 years) and 3 (OS = 5.9 years) had shorter OS than Clusters 2 (OS = not reached, Cluster 1: p < 0.001, Cluster 3: p < 0.001) and 4 (OS = not reached, Cluster 1: p = 0.004, Cluster 3: p < 0.001). Clusters 1 and 3 had a higher cumulative incidence of acute exacerbation than Clusters 2 (Cluster 1: p < 0.001, Cluster 3: p = 0.014) and 4 (Cluster 1: p < 0.001, Cluster 3: p = 0.006). Stratification by using clusters also independently predicted acute exacerbation (p < 0.001) and overall survival (p < 0.001). CONCLUSIONS: The high degree of disease heterogeneity of F-ILD can be underscored by four clusters based on clinical characteristics, which may be helpful in predicting the risk of fibrosis progression, acute exacerbation and overall survival.

Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.

BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. METHODS: Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. RESULTS: Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under -2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. CONCLUSION: ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH-targeted treatment for ACAN mutation-induced short stature. GH-promoting therapies may increase patients' heights.

Distribution and influencing factors on residual pockets of the teeth in patients with periodontitis following non-surgical periodontal treatment: a retrospective observational study.

BACKGROUND: Periodontitis is a chronic and multi-factorial infectious disease. A notable difference exists in the prognosis of patients with severe periodontitis after non-surgical periodontal treatment. Thus, a retrospective study was conducted to identify common and specific factors that impact the prognosis of patients with periodontitis stage III-IV following non-surgical periodontal treatment at different tooth sites. METHODS: A total of 977 teeth were included in the study, comprising 266 patients diagnosed with periodontitis stage III-IV. This sample included 330 anterior teeth, 362 maxillary posterior teeth, and 285 mandibular posterior teeth. Following treatment, the teeth were categorized into two groups based on residual pocket depth [probing depth (PD) ≥ 5 mm] at 3 months post-treatment. The prognosis of periodontitis stage III-IV was assessed through multivariate analysis employing logistic regression to determine the association of various risk factors. RESULTS: The PD values of each site and the deepest PD values of each tooth significantly decreased at 3 months post-treatment. Residual pockets were predominantly found in the mesio/disto-buccal and mesio/disto-lingual regions. Multivariate analysis revealed that gender, PD, sulcus bleeding index (SBI) and plaque index (PLI) at baseline, and crown-root ratio in anterior teeth had a significant influence on periodontitis stage III-IV (P < 0.05). Smoking, PD, PLI and furcation involvement (FI) at baseline, PLI at 3 months post-treatment, grades of periodontitis, and crown-root ratio were prediction factors for maxillary posterior teeth. Factors such as PD, PLI and FI at baseline, PLI at 3 months post-treatment, and crown-root were significant in mandibular posterior teeth. CONCLUSIONS: The outcome of non-surgical treatment varies depending on the tooth positions for patients with periodontitis stage III-IV. Dentists must accurately identify the affected teeth that have periodontal pockets of more than 5 mm, taking into consideration the positions of the affected teeth, as well as various local and systemic factors. This comprehensive assessment will enable dentists to develop a customized and effective treatment plan.

Pulmonary hypertension in patients with pneumoconiosis with progressive massive fibrosis.

OBJECTIVES: This study aims to explore the prevalence and clinical features of pulmonary hypertension (PH) in patients with progressive massive fibrosis (PMF) and its correlation with large opacities on CT scans. METHODS: This retrospective study collected 235 patients with PMF, and 199 were eligible for analysis. The probability of PH development was estimated based on tricuspid regurgitation velocity measured by echocardiogram. The size and the location of large opacities on chest CT were recorded. Potential risk factors for PH secondary to PMF were analysed using regression analysis. RESULTS: The prevalence of a high or intermediate probability of PH was 39.7% in patients with PMF. Type C of large opacities (OR 6.99, 95% CI 2.34 to 23.00, p<0.001) and central type of the large opacities (OR 8.12, 95% CI 2.89 to 24.71, p<0.001) were identified as the risk factors for PH secondary to PMF. Over a median follow-up of 32.8 months, the survival rate was 73.3% in the PH group, significantly lower than that in the non-PH group (96.6%, p<0.001). CONCLUSIONS: Over one-third of patients with PMF developed PH. The increased size and the central distribution of large opacities were identified as the risk factors.

Porphyromonas gingivalis survival skills: Immune evasion.

Periodontitis is a chronic inflammatory condition that destroys the tooth-supporting tissues and eventually leads to tooth loss. As one of the most prevalent oral conditions, periodontitis endangers the oral health of 70% of people throughout the world. Periodontitis is also related to various systemic diseases, such as diabetes mellitus, atherosclerosis, and rheumatoid arthritis, which not only has a great impact on population health status and the quality of life but also increases the social burden. Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. Porphyromonas gingivalis can express various of virulence factors to overturn innate and adaptive immunities, which makes P. gingivalis survive and propagate in the host, destroy periodontal tissues, and have connection to systemic diseases. Porphyromonas gingivalis can invade into and survive in host tissues by destructing the gingival epithelial barrier, internalizing into the epithelial cells, and enhancing autophagy in epithelial cells. Deregulation of complement system, degradation of antibacterial peptides, and destruction of phagocyte functions facilitate the evasion of P. gingivalis. Porphyromonas gingivalis can also suppress adaptive immunity, which allows P. gingivalis to exist in the host tissues and cause the inflammatory response persistently. Here, we review studies devoted to understanding the strategies utilized by P. gingivalis to escape host immunity. Methods for impairing P. gingivalis immune evasion are also mentioned.

Artificial stone-associated silicosis in China: A prospective comparison with natural stone-associated silicosis.

BACKGROUND AND OBJECTIVE: We recently noted a dramatic increase in the number of patients with accelerated silicosis associated with exposure to artificial stone dust. Therefore, the natural history of artificial stone-associated silicosis was compared with that of natural stone-associated silicosis. METHODS: A total of 18 patients with artificial stone-associated silicosis and 63 with natural stone-associated silicosis were diagnosed sequentially in 2018 and followed up for a period of 6-12 months. Data were collected from clinical charts. RESULTS: The median duration of exposure prior to onset of symptoms of silicosis was shorter for patients who had been exposed to artificial stone dust (6.4 vs 29.3 years, P < 0.01). Four of the 18 patients experienced rapid deterioration in lung function over the follow-up period, with declines in pre-bronchodilator FVC of 587 (210-960) mL/year and FEV1 of 625 (360-860) mL/year. GGO, PMF, emphysema and pulmonary artery widening were more frequently observed on computed tomography scans of patients with artificial stone-associated silicosis than of those with natural stone-associated silicosis. Approximately 38.9% of the patients with artificial stone-associated silicosis were lung transplant candidates and 27.8% died, both rates being significantly higher than in patients with natural stone-associated silicosis (3.2% and 0%, both P < 0.01). CONCLUSION: Compared to natural stone-associated silicosis, artificial stone-associated silicosis was characterized by short latency, rapid radiological progression, accelerated decline in lung function and high mortality.

Prevalence and determinants of metabolic syndrome based on three definitions in rural northeast China.

OBJECTIVE: To gain more comprehensive understanding of metabolic syndrome (Mets) among in general Chinese population. DESIGN: Cross-sectional study. Mets was defined by three widely accepted definitions including modified Adults Treatment Panel (ATP) III criteria, International Diabetes Federation (IDF) criteria and harmonized definition. Risk factors were evaluated by using multivariate logistic regression. SETTING: Nineteen rural villages in northeast China. PARTICIPANTS: The survey was conducted in September 2017 and May 2018 on 10 926 individuals. RESULTS: According to modified ATP III criteria, IDF criteria and harmonised definition, the overall prevalence of Mets was 41·3 % (95 % CI 40·3, 42·2), 34·2 % (95 % CI 33·2, 35·1) and 44·1 % (95 % CI 43·1, 45·1), respectively. Females had a higher prevalence, and elevated blood pressure was the most frequent. Age, female sex, non-peasant worker, higher BMI and lower-annual income were independent risk factors of Mets in all three definitions (all ps < 0·05). Based on modified ATP III criteria and harmonised definition, heavy drinking was positively correlated with Mets. In contrast, former drinking was inversely associated with Mets. CONCLUSIONS: Mets is highly prevalent in rural areas of northeast China. Its independent risk factors include higher age, female sex, non-peasantry worker, higher BMI and lower-annual income. Modified ATP III criteria and harmonised definition may be superior definitions of Mets.

Prevalence of first-degree atrioventricular block and the associated risk factors: a cross-sectional study in rural Northeast China.

BACKGROUND: First-degree atrioventricular block (AVB) has traditionally been regarded as a benign condition but recent studies have challenged this conception. Prevalence of 1-2% have been reported in developed countries in Asia. However, no epidemiologic studies have established the prevalence of first-degree AVB in developing countries. The aim of the study was to investigate the prevalence of first-degree AVB in rural northeast China and identify the associated risk factors. METHODS: This cross-sectional study was undertaken from September 2017 to May 2018 in rural areas of Liaoning Province. It involved 10,926 participants aged ≥40 years (85.3% of those who were eligible). First-degree AVB was confirmed by at least two independent cardiologists. Risk factors were evaluated using stepwise logistic regression. RESULTS: The prevalence of first-degree AVB was 3.4% (95% confidence interval [CI]: 3.0-3.8%). Males had a higher prevalence than females (5.1% vs. 2.2%, p < 0.001). The regression model involving all participants showed that age (odds ratio [OR]: 1.32; p <0.001), male sex (OR: 1.72; p = 0.001), height (OR: 1.25; p = 0.008), systolic blood pressure (SBP) (OR: 1.15; p = 0.003), triglycerides (TG) (OR: 1.10; p < 0.001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.73; p < 0.001), heart rate (OR: 0.78; p < 0.001), and exercising regularly (OR: 0.73; p = 0.030) were independent risk factors. CONCLUSIONS: First-degree AVB is highly prevalent in rural areas of northeast China. The associated independent risk factors include being male, older, and taller, higher SBP and TG, lower HDL-C and heart rate, and lack of exercise.

A Novel Ruthenium(II) Polypyridyl Complex Bearing 1,8-Naphthyridine as a High Selectivity and Sensitivity Fluorescent Chemosensor for Cu2+ and Fe3+ Ions.

A novel ruthenium(II) polypyridyl complex bearing 1,8-naphthyridine was successfully designed and synthesized. This complex was fully characterized by EI-HRMS, NMR, and elemental analyses. The recognition properties of the complex for various metal ions were investigated. The results suggested that the complex displayed high selectivity and sensitivity for Cu2+ and Fe3+ ions with good anti-interference in the CH3CN/H2O (1:1, v/v) solution. The fluorescent chemosensor showed obvious fluorescence quenching when the Cu2+ and Fe3+ ions were added. The detection limits of Cu2+ and Fe3+ were 39.9 nmol/L and 6.68 nmol/L, respectively. This study suggested that this Ru(II) polypyridyl complex can be used as a high selectivity and sensitivity fluorescent chemosensor for Cu2+ and Fe3+ ions.

Two star-shaped tetranuclear Ru(II) complexes containing uncoordinated imidazole groups: synthesis, characterization, photophysical and pH sensing properties.

Tetrapodal ligands H4L(1) and H4L(2) containing imidazole groups have been synthesized by the reaction of 1,10-phenanthroline-5,6-dione with 1,2,4,5-tetrakis[(4-formylphenoxy)methyl]benzene and 1,2,4,5-tetrakis[(3-formylphenoxy)methyl]benzene, respectively, in presence of NH4OAc. Two star-shaped complexes [{Ru(bpy)2}4(µ4-H4L(1))](PF6)8 and [{Ru(bpy)2}4(µ4-H4L(2))](PF6)8 (bpy = 2,2'-bipyridine) have been prepared by refluxing Ru(bpy)2Cl2 ·2H2O and each ligand in ethylene glycol. The deprotonated complexes [{Ru(bpy)2}4(µ4-L(1))](PF6)4 and [{Ru(bpy)2}4(µ4-L(2))](PF6)4 have been obtained by the reaction of sodium methoxide with [{Ru(bpy)2}4(µ4-H4L(1))](PF6)8 and [{Ru(bpy)2}4(µ4-H4L(2))](PF6)8, respectively, in methanol. The pH effects on the UV-vis light absorption and emission spectra of both complexes have been studied, and ground- and excited-state ionization constants of both complexes have been derived. The photophysical properties of both complexes are strongly dependent on the solution pH. They act as proton-induced off-on-off luminescent sensors through two successive deprotonation processes of imidazole groups, with a maximum on-off ratio of 8 in buffer solution at room temperature. Theoretical calculations for the highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LOMO) orbitals of bridging ligand are also presented for plausible explanations of the fluorescence changes.

Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis.

Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%-93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.

Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity.

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.

Pneumoconiosis combined with connective tissue disease in China: a cross-sectional study.

OBJECTIVE: To describe the prevalence, clinical features and potential risk factors of pneumoconiosis in combination with connective tissue disease (CTD) or positive autoantibodies. DESIGN: Cross-sectional study. SETTING: A retrospective study of adults recruited in China between December 2016 and November 2021. PARTICIPANTS: A total of 931 patients with pneumoconiosis at Beijing Chao-Yang Hospital were enrolled in this study; of these, 580 patients were included in the final analysis. MAIN OUTCOME MEASURES: Pneumoconiosis combined with CTD or positive autoantibodies was a major adverse outcome. RESULTS: In total, 13.8% (80/580) of the patients had combined pneumoconiosis with CTD, among whom the prevalence of CTD was 18.3% (46/251) in asbestosis and 11.4% (34/298) in silicosis/coal mine workers' pneumoconiosis. In comparison to the general Chinese adult population, the relative risk of various CTD in pneumoconiosis, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren's syndrome, idiopathic inflammatory myopathy and antineutrophil cytoplasmic antibodies-associated vasculitis, were 11.85, 12.12, 127.40, 4.23, 9.94 and 644.66, respectively. Multivariate analysis revealed that female sex (OR 2.55, 95% CI 1.56 to 4.17) and a later stage of pneumoconiosis (OR 2.04, 95% CI 1.24 to 3.34) were the independent risk factors for CTD in patients with pneumoconiosis (all p<0.050). CONCLUSION: CTD is highly prevalent in patients with pneumoconiosis, especially in patients of asbestosis, and silicosis/coal mine workers' pneumoconiosis. Female sex and later stages of pneumoconiosis are associated with an increased risk of combined with CTD.

Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study.

Objectives: Idiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP. Methods: This descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients' medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia. Results: A total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan-Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936-5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072-10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974-38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115-0.899, p = 0.031). Conclusion: Approximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.

Effect of electronic structure of energy transfer in bimetallic Ru(II)/Os(II) complexes.

Novel monometallic (µ-LL')Ru, Ru(µ-LL'), homobimetallic Ru(µ-LL')Ru, and heterodimetallic Ru(µ-LL')Os and Os(µ-LL')Ru complexes based on two asymmetrical ligands LL' (where LL' = L1L1', L2L2') have been synthesized and characterized. Spectroscopic analysis indicates that all complexes exhibit intense spin-allowed ligand-centered (LC) transitions at 288 nm and Ru-based moderate spin-allowed MLCT absorption between 440-450 nm. The Ru(µ-LL')Os and Os(µ-LL')Ru dinuclear complexes show Os-based unit absorption in the range of 565-583 nm. The Ru-based units of the complexes present different emission intensities due to differing steric hindrance at the coordination sites of the two bridging ligands. The Os(µ-LL')Ru dinuclear complexes present weaker emission intensity than their parent monometallic complexes (µ-LL')Ru. These results indicate that the emission of Os(µ-LL')Ru dinuclear complexes is quenched by the Os(II)-based units.