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Abstract Background In recent years, clinical cases of Chlamydia psittaci pneumonia have gradually increased. Chlamydia psittaci pneumonia can quickly progress to severe pneumonia, leading to respiratory failure. Chlamydia psittaci cannot be detected by commonly used detection methods, leading to difficulties in clinical diagnosis and treatment, which may eventually develop into severe Chlamydia psittaci pneumonia. Therefore, we should improve our diagnostic and treatment capabilities for this disease. Methods This article retrospectively studied 61 cases of pneumonia from 12 different provinces in China, and classified them into severe pneumonia and non-severe pneumonia. Divided into two groups, with 23 cases of severe pneumonia and 38 cases of non-severe pneumonia. We compared the two groups in terms of imaging, laboratory testing, treatment, prognosis, etc., hoping to provide better explanations and help clinical physicians better diagnose the disease. Results There is no difference in age, gender, contact history, smoking history, or basic disease between severe and non-severe Chlamydia psittaci pneumonia. The most prominent symptom is fever, with a median body temperature of 39.7 ℃, and other symptoms similar to common respiratory infections. White blood cells and neutrophils may not show significant elevation, but C-reactive protein (CRP) and procalcitonin (PCT) will both show significant elevation, often accompanied by a decrease in arterial oxygen pressure. Some patients may experience liver and kidney dysfunction, but there is no statistically significant difference between the two groups. Doxycycline remains the preferred drug for severe Chlamydia psittaci pneumonia. The imaging mainly shows consolidation and bronchial inflation sign, and may also present with pleural effusion. Conclusions The imaging of Chlamydia psittaci pneumonia usually shows consolidation with bronchial inflation sign, which can also be manifested as ground glass changes or solid masses. Atypical images are prone to misdiagnosis in the early stages. There are some differences in laboratory examination and imaging between severe pneumonia and non-severe pneumonia, which can help identify severe patients in the early stage. Metagenomic next-generation sequencing (mNGS) played an important role in the diagnosis of all cases in this article. Timely treatment has a good prognosis for the disease, and imaging lesions can be completely absorbed.

Generally, Cryptococcus initially infects the respiratory tract, but can spread, eventually crossing the blood-brain barrier (BBB) and causing meningitis or meningoencephalitis. Specifically, Cryptococcus invades the vascular endothelial cells of the BBB, from which it enters the brain. The main mechanisms through which Cryptococcus crosses the BBB are transcellular traversal, the paracellular pathway, and via Trojan horse. In this paper, the mechanisms by which Cryptococcus crosses the BBB were explained in detail. In addition to pathways of entry to the brain, this paper presents a discussion on some rare cryptococcal infections and provides some insights for future research directions.

Immune checkpoint inhibitors (ICIs) have changed the treatment mode of lung cancer, extending the survival time of patients unprecedentedly. Once patients respond to ICIs, the median duration of response is usually longer than that achieved with cytotoxic or targeted drugs. Unfortunately, there is still a large proportion of lung cancer patients do not respond to ICI. Effective biomarkers are crucial for identifying lung cancer patients who can benefit from them. The first predictive biomarker is programmed death-ligand 1 (PD-L1), but its predictive value is limited to specific populations. With the development of single-cell sequencing and spatial imaging technologies, as well as the use of deep learning and artificial intelligence, the identification of predictive biomarkers has been greatly expanded. In this review, we will dissect the biomarkers used to predict ICIs efficacy in lung cancer from the tumor-immune microenvironment and host perspectives, and describe cutting-edge technologies to further identify biomarkers.

Summary: Strains from the Cryptococcus gattii species complex (CGSC) have caused the Pacific Northwest cryptococcosis outbreak, the largest cluster of life-threatening fungal infections in otherwise healthy human hosts known to date. In this study, we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions, providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic clade. Phenotypic clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains, suggesting that shared determinants coordinate their adaptations to various stresses. Notably, a specific group of strains, including the outbreak isolates, exhibited a remarkable ability to adapt to all three of the most commonly used antifungal drugs for treating cryptococcosis (amphotericin B, 5-fluorocytosine, and fluconazole). By integrating pan-genomic and pan-transcriptomic analyses, we identified previously unrecognized genes that play crucial roles in conferring multidrug resistance in an outbreak strain with high multidrug adaptation. From these genes, we identified biomarkers that enable the accurate prediction of highly multidrug-adapted CGSC strains, achieving maximum accuracy and area under the curve (AUC) of 0.79 and 0.86, respectively, using machine learning algorithms. Overall, we developed a pan-omic approach to identify cryptococcal multidrug resistance determinants and predict highly multidrug-adapted CGSC strains that may pose significant clinical concern.

Abstract Cryptococcus is a family of strongly infectious pathogens that results in a wide variety of symptoms, particularly threatening the patients undergoing the immune‐deficiency or medical treatment. Rapidly identifying Cryptococcus subtypes and accurately quantifying their contents remain urgent needs for infection control and timely therapy. However, traditional detection techniques heavily rely on expensive, specialized instruments, significantly compromising their applicability for large‐scale population screening. In this work, we report a portable microwell array chip platform integrated with a deep learning‐based image recognition program, which enables rapid, precise quantification of the specific subtypes of Cryptococcus. The platform features four zones of microwell arrays preloaded with the subtype‐targeted CRISPR–Cas12a system that avoid dependence on slow, instrumental‐mediated target amplification, achieving rapid (10 min), high specificity for identifying the sequence of Cryptococcus. The deep learning‐based image recognition program utilizing segment anything model (SAM) significantly enhances automation and accuracy in identifying target concentrations, which eventually achieves ultra‐low limit of detection (0.5 pM) by personal smartphones. This platform can be further customized to adapt to various scenarios in clinical settings.

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. Materials and methods The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. Results Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). Conclusions In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

Abstract Background Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear. Objective The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations. Data and methods Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically. Results Forty‐three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included ‘falling snowflake sign’, ground‐glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet‐like shape (tall column‐like shape) and quasi‐circular shape. Tall column‐shaped tumour cells were negative or weakly positive for thyroid transcription factor‐1 (TTF‐1) and strongly positive for ALK mutation, whereas quasi‐circular tumour cells were positive for TTF‐1 and less positive for ALK mutation. Conclusion The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF‐1 and ALK genes affect the production of mucus.

Abstract The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

ABSTRACT Cryptococcus gattii (C. gattii) is emerging as a life-threatening fungus worldwide. However, few data were available in China. In this study, 27 isolates and 32 patient information were collected from several hospitals in China, together with previously reported data (80 cases), to describe the geographic distribution of C. gattii. Molecular identification and genetic diversity analysis of the isolates were conducted using multilocus sequence typing, while the microbiological and virulence characteristics were explored through in vitro phenotypic tests and in vivo animal experiments. The findings revealed that patients infected with C. gattii were mainly immunocompetent males, with most showing symptoms of central nervous system involvement. Isolated strains were predominantly distributed in tropical and subtropical regions, with VGI genotype predominance. These strains exhibited marked genetic diversity, identifying 25 distinct sequence types (STs) among the 57 isolates (available data), including three novel STs (ST565, ST567, and ST568). In vitro assays unveiled significant differences between VGI and VGII in growth capacity at 39°C, capsule diameter, melanin production, UV resistance, and antioxidative capacity, with VGII displaying greater resilience. Integrating animal experiments and clinical prognosis showed that pathogenicity did not directly correlate with in vitro virulence phenotypes or molecular genotypes, underscoring virulence’s complexity. Furthermore, histopathological analysis suggested that lung tissue damage might primarily contribute to mouse mortality, particularly with more pathogenic strains causing extensive lung tissue damage. Our study has the potential to provide valuable data for a comprehensive understanding of the microbiological characteristics of C. gattii in China. IMPORTANCE Our study indicates that the molecular typing of Cryptococcus gattii is unrelated to virulence. The integration of animal experiments and clinical prognosis demonstrated that pathogenicity did not exhibit a direct correlation with in vitro virulence phenotypes or molecular genotypes, emphasizing the intricate nature of virulence. In conclusion, our research holds the potential to provide valuable insights into understanding the microbiological attributes of C. gattii in China.

Abstract Background With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. Methods The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. Results 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. Conclusion We found that glucocorticoid 1–2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

Abstract Background Part-solid nodules (PSNs) have gradually shifted to defining special clinical subtypes. Commonly, the solid portions of PSNs show various radiological morphologies, of which the corresponding pathological basis and prognosis are unclear. We conducted a radiological–pathological evaluation to determine the histopathologic basis of different consolidation radiographic morphologies related to prognosis. Materials and methods A cohort of 275 patients with a surgical pathological diagnosis of lung adenocarcinoma were enrolled. Preoperative computed tomography (CT) images of the PSNs were recorded and assessed. A panel of 103 patients with complete pathological specimens was selected to examine the radiological–pathological associations, and follow-up was performed to identify the prognosis. Results Of the 275 patients, punctate consolidation was observed radiologically in 43/275 (15.7%), stripe consolidation in 68/275 (24.7%), and irregular consolidation in 164/275 (59.6%) patients. The radiological morphology of the solid components was significantly associated with the histopathological subtypes (P

Abstract Objective Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC. Methods and Materials A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated. Results A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground‐glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part‐solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35–7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02–5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4–0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026). Conclusions We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management.

Abstract Objectives There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on radiologic-pathologic comparison and to study the prognosis. Methods The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison. Results According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435–23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349–90.623, P = 0.025) were two independent risk factors for tumor progression. Conclusions PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment.

Cryptococcus is an invasive fungus that seriously endangers human life and health, with a complex and well-established immune-escaping mechanism that interferes with the function of the host immune system. Cryptococcus can attenuate the host’s correct recognition of the fungal antigen and escape the immune response mediated by host phagocytes, innate lymphoid cells, T lymphocytes, B lymphocytes with antibodies, and peripheral cytokines. In addition, the capsule, melanin, dormancy, Titan cells, biofilm, and other related structures of Cryptococcus are also involved in the process of escaping the host’s immunity, as well as enhancing the ability of Cryptococcus to infect the host.

To avoid the aimless design of shaped charge liner (SCL) material for obtaining deep penetration and large penetration holes in reinforced concrete targets, new design principles are proposed in this study. Following the principles, an intermetallic-compound-reinforced Ti-17Al-29Nb alloy was prepared via hot isostatic pressing (HIP) sintering. This alloy shows high dynamic compressive strength (1583 MPa), high dynamic compressive plasticity (35 %), high elevated-temperature tensile strength (414 MPa at 800 °C), and low elevated-temperature plasticity (6 % at 800 °C). The penetrating experiments showed that the Ti-17Al-29Nb alloy liner penetrated through the 600-mm-thick C40 concrete target, forming large penetration holes. Although the penetration depth was slightly lower than that of the most commonly used pure copper liner, the diameter of the exit hole was 2.1 times that of the pure copper liner. The high jet tip velocity (7651 m/s) and large jet diameter (a maximum of 0.28 CD) were the key factors to form the high penetration depth and large penetration hole. This study not only brings a new type of SCL material with excellent penetration performance against reinforced concrete targets but also provides a new research direction for the design and selection of the SCL materials.

PIWI-interacting RNAs (piRNAs) are a less-studied class of small non-coding RNAs approximately 24–31 nucleotides in length. They express in germline and somatic cells and form complexes with PIWI proteins to exert regulatory effects. New studies show that piRNAs are aberrantly expressed in various cancers. In this review, we focus on those piRNAs that are associated with cancer hallmarks such as proliferation, invasion, and chemoresistance and discuss their potential as biomarkers for cancer diagnosis and prognosis.

Reactive structural materials are of interest in military applications due to their impact-initiated characteristics. The determination of critical impact velocity is of crucial importance in designing munitions to produce a maximum destructive effect on the target upon impact. Here, combining high-speed photography and image processing technique, we demonstrate an approach to determine the critical impact velocity through quantitatively assessing the energy-release characteristics of a Zr-Ti-Nb reactive alloy under high-speed impact. The Zr-Ti-Nb alloy is fabricated by powder metallurgy and has high strength and sufficient ductility under dynamic loading. By conducting a series of ballistic impact experiments, the relationship between the impact velocity of alloy projectiles and light emission from burning fragments is obtained and discussed. Two critical impact velocities are determined. The first represents the minimum impact velocity required for initiating the intense exothermic reaction of the alloy projectiles, while the second denotes the impact velocity when the extent of reaction reached the maximum. By analyzing the fragments recovered at different velocities, it is proved that the fragmentation behavior of the alloy projectiles is found to be highly dependent on the impact velocity. This results in obvious different energy-releasing characteristics of Zr-Ti-Nb alloy, and the corresponding mechanism was also discussed.

Ferroptosis is a more relatively recently identified type of programmed cell death, which is associated with tumor progression. However, the mechanism underlying the effect of ferroptosis-related long non-coding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) remains elusive. Therefore, the current study aimed to investigate the role of ferroptosis-related lncRNAs in LUAD and to develop a prognostic model. The clinicopathological characteristics of patients and the gene sequencing data were obtained from The Cancer Genome Atlas, while the ferroptosis-associated mRNAs were downloaded from the FerrDb database. A ferroptosis-related lncRNA signature was established with Least Absolute Shrinkage and Selection Operator Cox regression analysis. Furthermore, the risk scores of ferroptosis-related lncRNAs were calculated and LUAD patients were then assigned to high- and low-risk groups based on the median risk score. The prognostic model was established by K-M plotters and nomograms. Gene set enrichment analysis (GSEA) was performed to evaluate the association between immune responses and ferroptosis-related lncRNAs. A total of 10 ferroptosis-related lncRNAs were identified as independent predictors of LUAD outcome, namely RP11-386M24.3, LINC00592, FENDRR, AC104699.1, AC091132.1, LANCL1-AS1, LINC-PINT, IFNG-AS1, LINC00968 and AC006129.2. The area under the curve verified that the established signatures could determine LUAD prognosis. The nomogram model was used to assess the predictive accuracy of the established signatures. Additionally, GSEA revealed that the 10 ferroptosis-related lncRNAs could be involved in immune responses in LUAD. Overall, the results of the current study may provide novel insights into the development of novel therapies or diagnostic strategies for LUAD.

Abstract Background Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis. Methods We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP. Results CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P

Immunotherapy, the reactivation of the immune system to recognize cancer cells, can be accompanied by severe adverse effects. Here, the authors use pharmacovigilance and genomic data to be able to predict which patients might be susceptible to such severe events.

Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China.

Electrocatalytic urea oxidation reaction (UOR) is regarded as an effective yet challenging approach for the degradation of urea in wastewater into harmless N2 and CO2. To overcome the sluggish kinetics, catalytically active sites should be rationally designed to maneuver the multiple key steps of intermediate adsorption and desorption. Herein, we demonstrate that metal-organic frameworks (MOFs) can provide an ideal platform for tailoring binary active sites to facilitate the rate-determining steps, achieving remarkable electrocatalytic activity toward UOR. Specifically, the MOF (namely, NiMn0.14-BDC) based on Ni/Mn sites and terephthalic acid (BDC) ligands exhibits a low voltage of 1.317 V to deliver a current density of 10 mA cm-2. As a result, a high turnover frequency (TOF) of 0.15 s-1 is achieved at a voltage of 1.4 V, which enables a urea degradation rate of 81.87% in 0.33 M urea solution. The combination of experimental characterization with theoretical calculation reveals that the Ni and Mn sites play synergistic roles in maneuvering the evolution of urea molecules and key reaction intermediates during the UOR, while the binary Ni/Mn sites in MOF offer the tunability for electronic structure and d-band center impacting on the intermediate evolution. This work provides important insights into active site design by leveraging MOF platform and represents a solid step toward highly efficient UOR with MOF-based electrocatalysts.

Objective This study aimed to compare the clinical features of pulmonary cryptococcosis (PC) in patients with and without central nervous system (CNS) involvement. Methods We retrospectively reviewed demographics, presenting symptoms, radiographic features, and laboratory findings of patients diagnosed with PC in 28 hospitals from 2010 to 2019. Risk factors for CNS involvement were analyzed using logistic regression models. Result A total of 440 patients were included, and 36 (8.2%) had CNS involvement. Significant differences in fever, headache, and chills occurred between the two groups (overall and with/without CNS involvement) for fever (17.8% [78/440]; 52.8% vs. 14.6% of patients, respectively), headache (4.5% [20/440]; 55.6% vs. 0% of patients, respectively), and chills (4.3% [19/440]; 13.9% vs. 3.5% of patients, respectively). The common imaging manifestation was nodules (66.4%). Multivariate analysis showed that cavitation (adjusted odds ratio [AOR] = 3.552), fever (AOR = 4.182), and headache were risk factors for CNS involvement. Routine blood tests showed no differences between the groups, whereas in cerebrospinal fluid the white blood cell count increased significantly and glucose decreased significantly. Conclusion In patients with PC, the risk of CNS involvement increases in patients with headache, fever, and cavitation; these unique clinical features may be helpful in the diagnosis.

Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-induced neurodegeneration and underlying mechanisms. Aged C57BL/6 mice (20 months old) were exposed to isoflurane (1.5%) anesthesia for 6 h. Atorvastatin (5, 10, or 20 mg/kg body weight) was administered to the mice for 7 days. Atorvastatin attenuated the isoflurane-induced generation of ROS and apoptosis. Western blotting revealed a decrease in cleaved caspase-9 and caspase-3 expression in line with ROS levels. Furthermore, atorvastatin ameliorated the isoflurane-induced activation of p38MAPK/ATF-2 signaling. In a cellular study, we proved that isoflurane could induce oxidative stress and inflammation by activating the p38MAPK/ATF-2 pathway in BV-2 microglia cells. In addition, SB203580, a selected p38MAPK inhibitor, inhibited the isoflurane-induced inflammation, oxidative stress, and apoptosis. The results implied that p38MAPK/ATF-2 was a potential target for the treatment of postoperative cognitive dysfunction.

Objective This study was performed to compare the radiologic characteristics and pathological presentations of primary pulmonary lymphoma (PPL), explore the possible mechanism underlying its development, summarize its radiologic characteristics, and improve the accuracy of its diagnosis. Methods The medical records of 22 patients pathologically diagnosed with PPL were retrospectively analyzed. Results Chest computed tomography (CT) demonstrated single or multiple nodules and masses in the lungs, patchy opacities or consolidation along the bronchovascular bundle, and no significantly enlarged mediastinal or hilar lymph nodes. All 22 cases of PPL were classified as non-Hodgkin’s lymphoma (NHL) by transbronchial biopsy, CT-guided needle biopsy, and postoperative pathology. Most (16 cases) were marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). Twelve patients had air bronchograms within the lesion, and 13 showed ill-defined lesions with ground-glass brush-like changes. Conclusion PPL is a rare lung tumor, and most are classified as MALT lymphoma, a subtype of NHL. Chest CT can help to diagnose this disease. Positron emission tomography (PET)/CT is of great clinical value for evaluation of the lesion and patient’s general condition. The possibility of PPL should be considered in patients with characteristic CT and PET/CT findings and mild clinical symptoms, and early treatment should be administered.

Background: Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations.Patients and Methods: A retrospective data acquisition was conducted spanning 6 years (2013–2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria.Results: 1081 patients (62.49%) harbored EGFR mutation. ALK (n = 42, 2.43%), KRAS (n = 201, 11.62%), CTNNB1 (n = 28, 1.62%), BRAF (n = 31, 1.79%), PIK3CA (n = 51, 2.95%), MET (n = 14, 0.81%), HER2 (n = 47, 2.72%), HRAS (n = 3, 0.17%), and other genes(n = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%.Conclusion: We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China.

Three multi-oxidants reactive materials (59PTFE-23Al–18Bi2O3, 59PTFE-26Al–15Fe2O3, and 59PTFE-27Al–14MoO3) were prepared and the effect of metal oxides on the reaction characteristics was systematically investigated. Reaction energy, burning speed, and specific volume of explosive were measured, and the dynamic mechanical properties were characterized by the split-Hopkinson pressure bar. The reaction processes under high strain rate and high-speed impact were recorded by the high-speed camera. Our results indicate that the Bi2O3 is the most effective oxidant in increasing the reaction efficiency of the PTFE-Al system, which leads to the largest combustion flare and longest reaction time under high strain rate and high-speed impact. Furthermore, we demonstrate that the 59PTFE-23Al–18Bi2O3 has the best penetration performance at a speed of 1200 m/s due to its high gas production rate compared to the other systems. Keywords: Reactive materials, Multi-oxidants, Reaction characteristics, Destructive effect

Adding an appropriate interfacial layer is a viable way to decrease the WW contiguity and enhance the interfacial bonding of WCu alloy simultaneously, hence increase the tensile ductility. In this regard, we prepared a new kind of WMoCu alloy with transition phase (TP) existing between W particles and Cu matrix using infiltration method. The TP consisting of amorphous and nanocrystalline structure is formed between the W particles and the Cu matrix. The formation of the TP simultaneously decreases the WW contiguity and enhances bonding with both W particles and Cu matrix, leading to the good tensile ductility of the WMoCu alloy. The underlying formation mechanism of the TP is thoroughly studied. The WMoCu alloy exhibits excellent ductility under both compressive and tensile loading at room temperature. Under the quasi-static tensile loading, the critical failure strain of the WMoCu alloy is 0.18. Our analysis demonstrates that a strong bonding is formed between the TP and the adjacent phases. Keywords: WMoCu alloy, Transition phase, Amorphous and nanocrystalline phase, Interfacial bonding, Tensile ductility

Objective Diagnosis of pulmonary cryptococcosis is difficult. In this study, we examined the clinical and radiological features that increase the diagnostic accuracy for pulmonary cryptococcosis. Methods This retrospective study included clinical data from 68 patients with pulmonary cryptococcosis from 2012 to 2016 in 3 tertiary hospitals. Results Among the 68 patients, 39 (57.35%) had no complications, 39 (57.35%) had clinical symptoms, 6 (8.82%) had a history of occupational exposure, 27 (39.71%) had a single nodule/mass (the most common type of pulmonary cryptococcosis) on chest computed tomography images, 21 (30.88%) had multiple nodules/masses, 16 (23.53%) had ground glass opacity with or without nodules, 2 (2.94%) had miliary nodules, and 2 (2.94%) had enlarged mediastinal lymph nodes. Fifty-three (77.94%) patients had lesions with irregular margins, 33 (48.53%) had spiculated lesions, 32 (47.06%) had air bronchograms, 9 (13.24%) had cavities, and 4 (5.88%) had calcifications. Twenty-four patients underwent surgery, 35 received antifungal treatment, and 9 received both treatments. Conclusion The clinical features and computed tomography signs found in this study are not specific for a diagnosis of pulmonary cryptococcosis. Therefore, an increased awareness of pulmonary cryptococcosis is needed among clinicians.

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

Due to its negligible solubility, it is difficult to obtain a W-30Cu composite with a homogenous microstructure. However, with a selected W skeleton, a homogeneous phase distribution was achieved for a W-30Cu composite in the present study. By detailed characterization of the mechanical performance and microstructure of the W-30Cu composite, as well as the stress distribution state under a loading condition, the effects of microstructure homogeneity on the mechanical properties and failure mechanisms are identified. The mechanisms by which the ductility and strength depend on microstructure homogeneity contain the effects on plastic deformation and stress coordination of the Cu phase network. The dominant factors for the high ductility and strength of W-30Cu composites are proposed.