Performance of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of invasive pulmonary filamentous fungi infections in non-neutropenic patients.

The diagnosis of invasive pulmonary fungal disease depends on histopathology and mycological culture; there are few studies on touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of pulmonary filamentous fungi infections. The purpose of the present study was to explore the detection accuracy of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the filamentous fungi, and it aims to provide a basis for initiating antifungal therapy before obtaining microbiological evidence. We retrospectively analyzed the diagnosis and treatment of 44 non-neutropenic patients with invasive pulmonary filamentous fungi confirmed by glactomannan assay, histopathology, and culture from February 2017 to December 2023. The diagnostic positive rate and sensitivity of rapid on-site evaluation for these filamentous fungi identification, including diagnostic turnaround time, were calculated. Compared with the final diagnosis, the sensitivity of rapid on-site evaluation was 81.8%, and the sensitivity of histopathology, culture of bronchoalveolar lavage fluid, and glactomannan assay of bronchoalveolar lavage fluid was 86.4%, 52.3%, and 68.2%, respectively. The average turnaround time of detecting filamentous fungi by rapid on-site evaluation was 0.17 ± 0.03 hours, which was significantly faster than histopathology, glactomannan assay, and mycological culture. A total of 29 (76.3%) patients received earlier antifungal therapy based on ROSE diagnosis and demonstrated clinical improvement. Rapid on-site evaluation showed good sensitivity and accuracy that can be comparable to histopathology in identification of pulmonary filamentous fungi. Importantly, it contributed to the triage of biopsies for further microbial culture or molecular detection based on the preliminary diagnosis, and the decision on early antifungal therapy before microbiological evidence is available.

Urinary C4d and progression of kidney disease in IgA vasculitis.

BACKGROUND: IgA vasculitis nephritis is the most common secondary IgA nephropathy. Urinary C4d have been identified associated with the development and progression in primary IgA nephropathy. However, its role in kidney disease progression of IgA vasculitis nephritis is still unclear. METHODS: This study enrolled 139 patients with IgA vasculitis nephritis (IgAVN), 18 healthy subjects, 23 Focal segmental glomerulosclerosis patients and 38 IgA nephropathy (IgAN) patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% eGFR decline or ESKD, was assessed using Cox proportional hazards models and restricted cubic splines. RESULTS: The levels of urinary C4d/creatinine in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/creatinine were associated with higher proteinuria and severe Oxford C lesions and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of ln (urinary C4d/creatinine). After adjustment for clinical data, higher levels of urinary C4d/creatinine were associated with kidney disease progression in IgA vasculitis nephritis (per ln transformed urinary C4d/creatinine, hazard ratio (HR) =1.573, 95% confidence interval (CI) 1.101-2.245; P = 0.013). Compared to the lower C4d/creatinine group, hazard ratio was 5.539(95%CI, 1.135-27.035; P = 0.034) for the higher levels group. CONCLUSIONS: Higher levels of urinary C4d/creatinine were associated with kidney disease progression event in patients IgAVN.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

The mediating role of psychological capital on the relationship between perceived stress and self-directed learning ability in nursing students.

BACKGROUND: As indispensable reserves for the nursing workforce, undergraduate nursing students must possess self-directed learning abilities to consistently update their professional knowledge and adapt to the evolving demands of professional development. The acquisition of self-directed learning abilities can help undergraduate nursing students augment their theoretical knowledge and refine their clinical practice skills, thus fulfilling the demand from patients for high-quality nursing services. Hence, comprehending and investigating the factors that influence the development of self-directed learning abilities in nursing students is of paramount importance for nursing education and advancement of the nursing profession. OBJECTIVES: This study investigated the status of and associations between perceived stress, psychological capital, and self-directed learning abilities among undergraduate nursing students. Additionally, it examines the mediating role of psychological capital in the relationship between perceived stress and self-directed learning abilities. Thus, aiming to provide nursing educators with new directions for enhancing self-directed learning abilities. DESIGN: A cross-sectional descriptive study. METHODS: In February and March 2023, 900 undergraduate nursing students from 10 nursing schools completed an online questionnaire. The questionnaire included measures of perceived stress, psychological capital, and self-directed learning ability. Data were analyzed using SPSS 27.0 and the PROCESS macro tool. RESULTS: The scores for perceived stress, psychological capital, and self-directed learning ability among undergraduate nursing students were 40.07 ± 5.90, 99.89 ± 16.59, and 87.12 ± 9.20, respectively. Self-directed learning abilities were negatively correlated with perceived stress (r = -0.415, p < 0.001) and positively correlated with psychological capital (r = 0.465, p < 0.001). Perceived stress was negatively correlated with psychological capital (r = -0.630, p < 0.001). Psychological capital partially mediated the relationship between perceived stress and self-directed learning abilities among undergraduate nursing students, with a mediation effect of -0.166, accounting for 49.55% of the total effect. CONCLUSION: This study found that undergraduate nursing students perceived high levels of stress, possessed low levels of psychological capital, and had moderate levels of self-directed learning. Perceived stress and psychological capital directly influenced undergraduate nursing students' self-directed learning abilities, and perceived stress indirectly affected self-directed learning abilities through psychological capital. Nursing managers and educators should alleviate the perceived stress of undergraduate nursing students and cultivate their positive psychological capital to enhance self-directed learning abilities.

A Daily Diary Study of the Reciprocal Relation between Parental Psychological Aggression and Adolescent Anxiety in China.

The daily reciprocal relations between parental psychological aggression and adolescent anxiety and the heterogeneity, i.e., whether these relations vary across different adolescents, remain unclear. This study examined this issue with a 15-day daily diary study among 326 Chinese adolescents (Mage = 14.53 years, SD = 0.60, 47.2% girls). Dynamic structural equation models revealed that parental psychological aggression co-fluctuated with adolescent anxiety within a day. For lagged associations, only father-driven effects were supported but not mother-driven effects, whereas child-driven effects were supported for both parents. These within-person associations were heterogeneous across adolescents. Moreover, adolescents with more parental psychological aggression reported higher anxiety. This study revealed the reciprocal relations between parental psychological aggression and adolescent anxiety at the micro timescale and also highlighted that the within-person associations were heterogeneous across different adolescents.

Oxygen-Vacancy-Engineered W18 O49-x Nanobrush with a Suitable Band Structure for Highly Efficient Sonodynamic Therapy.

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound-based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen-vacancy-engineered W18 O49-x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18 O49-x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1 O2 ), superoxide anions (⋅O2 - ), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron-hole recombination are incidentally introduced through one-step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen-vacancy-engineered W18 O49-x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT.

Glutathione Induced In situ Synthesis of Cu Single-Atom Nanozymes with Anaerobic Glycolysis Metabolism Interference for Boosting Cuproptosis.

Single-atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu-O2/Cu-O4) via GSH-responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase-like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off-target effects of SACs-induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis-associated therapies.

Iridium-Catalyzed Asymmetric Allylic Substitution Reaction of 4-Hydroxypyran-2-one.

Pyranones have raised great concerns owing to their considerable applications in a variety of sectors. However, the development of direct asymmetric allylation of 4-hydroxypyran-2-ones is still restricted. Herein, we present an effective iridium-catalyzed asymmetric functionalization technique for the synthesis of 4-hydroxypyran-2-one derivatives over direct and efficient catalytic asymmetric Friedel-Crafts-type allylation by using allyl alcohols. The allylation products could be obtained with good to high yields (up to 96%) and excellent enantioselectivities (>99% ee). Therefore, the disclosed technique provides a new asymmetric synthetic strategy to explore pyranone derivatives in depth, thus providing an interesting approach for global application and further utilization in organic synthesis and pharmaceutical chemistry.

The predictive value of Berden's classification versus renal risk score for renal survival of Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

OBJECTIVES: This study aims to compare the prognostic values of two histopathological classification, Berden's classification versus renal risk score (RRS) by Brix et al. for predicting renal survival in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (MPO-AAGN). METHODS: The medical records of 225 patients with MPO-AAGN diagnosed in our centre between February 2004 and December 2020 were retrospectively analysed. The predictive model of Berden's classification or RRS was established by Cox regression, respectively. The above two models were compared on aspects of discrimination, calibration, and decision curve analysis for predicting the 0.5-, 1-, 3-, and 5-year renal survival. RESULTS: After a median follow up of 38.99 months, 32.44% of patients developed end-stage renal disease (ESRD). In the Kaplan-Meier analysis, there were significant differences in renal survival among groups according to Berden's classification or RRS (both log-rank p<0.001). According to time-dependent receiver operating characteristic (ROC) curve analysis, the model based on RRS showed better discrimination ability than the model based on Berden's classification for predicting 0.5-, 1-, and 3-year renal survival. For calibration analysis, the model based on RRS showed worse calibration than the model based on Berden's classification for predicting 1- and 3-year renal survival. According to the decision curve analysis, the clinical decisions based on RRS could achieve more clinical benefits than those based on Berden's classification in predicting 0.5-, 1-, and 3-year renal survival. CONCLUSIONS: The model based on RRS has better predictive value for renal survival than Berden's classification in aspect of discrimination and clinical decision from 0.5- to 3-year renal survival.

Ultrathin Carbon Nitride Nanosheets Exfoliated and In Situ Modified with a Nickel Bis(Chelate) Complex for Boosting Photocatalytic Performances.

Exfoliation and interfacial modification of two-dimensional (2D) polymeric carbon nitride (CN) are considerably vital for applications in photo/electrocatalysis fields. Here, a grinding-ultrasonic route was designed to construct nickel bis(chelate) complex (Ni(abt)2, abt = 2-aminobenzenethiolate)-modified CN ultrathin nanosheets. Under the assistance of the shear force derived from the grinding process, Ni(abt)2 was implanted into the interlamination of bulk CN, resulting in the formation of ultrathin CN (UCN) nanosheets. Simultaneously, Ni(abt)2 molecules were anchored on the surfaces of as-formed UCN nanosheets due to the π-π stacking interaction. Interestingly, compared with single Ni(abt)2 and UCN, the as-obtained Ni(abt)2/UCN nanosheets exhibited excellent photocatalytic hydrogen evolution capability. A molecule-semiconductor internal electron transmission mechanism was suggested for explaining the separation and transfer of electron-hole pairs. Density functional theory (DFT) calculations demonstrated that the interface-induced electron redistribution tuned the electron density and hydrogen adsorption of the active centers, thus enhancing the photocatalytic performance of the hybrid catalyst. In addition, the as-obtained Ni(abt)2/UCN nanosheets could also catalyze the reduction of nitroaromatics in the presence of NaBH4. It was found that under the simulated sunlight irradiation, the conversion efficiency of nitroaromatic compounds to amino aromatic ones was up to 97.3%, far higher than that under the condition without light irradiation (51.7%), suggesting that the photocatalytic-produced hydrogen took part in the reduction of nitroaromatic compounds.

Patient-Reported Outcomes in Young Adults with Myeloproliferative Neoplasms.

INTRODUCTION: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare. METHODS: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years). RESULTS: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment. CONCLUSIONS: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients.

Laser-triggered intelligent drug delivery and anti-cancer photodynamic therapy using platelets as the vehicle.

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals.

What is the context?1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro.2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets.3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm).4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells.What is new?1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug.2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets.3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo.4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions.What is impact?The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.

A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation.

Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings are unsymmetrically substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach to axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The desired diaryl ethers could be obtained in moderate to good chemical yields (up to 79 %) and high enantioselectivities (up to 95 % ee) under standard reaction conditions. Such structural motifs are interesting precursors for further transformations and may have potential applications in the synthesis of chiral ligands or catalysts.

A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin.

BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.

Performance of rapid on-site evaluation of touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BACKGROUND AND OBJECTIVE: The diagnosis of pulmonary cryptococcosis depends on serum testing, histopathology and mycological culture; there are few studies on touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. The purpose of the current study was to investigate the accuracy and timeliness of on-site touch imprint cytology in the diagnosis of pulmonary cryptococcosis during CT-guided percutaneous lung biopsy. METHODS: We retrospectively analysed the diagnosis and treatment of 56 patients with final proof of pulmonary cryptococcosis through histopathology and culture or surgical resection from September 2015 to February 2021. Diagnostic methods and treatment and the turnaround time for diagnosis were analysed. RESULTS: The sensitivity of rapid on-site evaluation was 89.3%, and the sensitivity of serology, histopathology and mycological culture was 53.6%, 91.1% and 61.5%, respectively, compared with the final diagnosis. The average turnaround time to diagnose pulmonary cryptococcosis by on-site touch imprint cytology was 8.3 ± 0.9 min, which was significantly faster than serum testing, histopathology and mycological culture. CONCLUSION: On-site touch imprint cytology showed good sensitivity and timeliness in the diagnosis of pulmonary cryptococcosis. In addition, it contributed to the triage of biopsies based on the preliminary diagnosis. On-site touch imprint cytology should be applied and promoted in the diagnosis of pulmonary cryptococcosis during biopsy.

Disposable Electrochemical Sensors for Highly Sensitive Detection of Chlorpromazine in Human Whole Blood Based on the Silica Nanochannel Array Modified Screen-Printed Carbon Electrode.

Rapid and highly sensitive quantitative analysis of chlorpromazine (CPZ) in human whole blood is of great importance for human health. Herein, we utilize the screen-printed carbon electrodes (SPCE) as the electrode substrates for growth of highly electroactive and antifouling nanocomposite materials consisting of vertically ordered mesoporous silica films (VMSF) and electrochemically reduced graphene oxide (ErGO) nanosheets. The preparation of such VMSF/ErGO/SPCE could be performed by using an electrochemical method in a few seconds and the operation is controllable. Inner ErGO layer converted from graphene oxide (GO) in the growth process of VMSF provides oxygen-containing groups and two-dimensional π-conjugated planar structure for stable fabrication of outer VMSF layer. Owing to the π-π enrichment and excellent electrocatalytic abilities of ErGO, electrostatic preconcentration and antifouling capacities of VMSF, and inherent disposable and miniaturized properties of SPCE, the proposed VMSF/ErGO/SPCE sensor could be applied for quantitative determination of CPZ in human whole blood with high accuracy and sensitivity, good stability, and low sample consumption.

Elevated postischemic tissue injury and leukocyte-endothelial adhesive interactions in mice with global deficiency in caveolin-2: role of PAI-1.

Ischemia/reperfusion (I/R)-induced rapid inflammation involving activation of leukocyte-endothelial adhesive interactions and leukocyte infiltration into tissues is a major contributor to postischemic tissue injury. However, the molecular mediators involved in this pathological process are not fully known. We have previously reported that caveolin-2 (Cav-2), a protein component of plasma membrane caveolae, regulated leukocyte infiltration in mouse lung carcinoma tumors. The goal of the current study was to examine if Cav-2 plays a role in I/R injury and associated acute leukocyte-mediated inflammation. Using a mouse small intestinal I/R model, we demonstrated that I/R downregulates Cav-2 protein levels in the small bowel. Further study using Cav-2-deficient mice revealed aggravated postischemic tissue injury determined by scoring of villi length in H&E-stained tissue sections, which correlated with increased numbers of MPO-positive tissue-infiltrating leukocytes determined by IHC staining. Intravital microscopic analysis of upstream events relative to leukocyte transmigration and tissue infiltration revealed that leukocyte-endothelial cell adhesive interactions in postcapillary venules, namely leukocyte rolling and adhesion were also enhanced in Cav-2-deficient mice. Mechanistically, Cav-2 deficiency increased plasminogen activator inhibitor-1 (PAI-1) protein levels in the intestinal tissue and a pharmacological inhibition of PAI-1 had overall greater inhibitory effect on both aggravated I/R tissue injury and enhanced leukocyte-endothelial interactions in postcapillary venules in Cav-2-deficient mice. In conclusion, our data suggest that Cav-2 protein alleviates tissue injury in response to I/R by dampening PAI-1 protein levels and thereby reducing leukocyte-endothelial adhesive interactions.NEW & NOTEWORTHY The role of caveolin-2 in regulating ischemia/reperfusion (I/R) tissue injury and the mechanisms underlying its effects are unknown. This study uses caveolin-2-deficient mouse and small intestinal I/R injury models to examine the role of caveolin-2 in the leukocyte-dependent reperfusion injury. We demonstrate for the first time that caveolin-2 plays a protective role from the I/R-induced leukocyte-dependent reperfusion injury by reducing PAI-1 protein levels in intestinal tissue and leukocyte-endothelial adhesive interactions in postcapillary venules.

A Multifunctional Nanovaccine based on L-Arginine-Loaded Black Mesoporous Titania: Ultrasound-Triggered Synergistic Cancer Sonodynamic Therapy/Gas Therapy/Immunotherapy with Remarkably Enhanced Efficacy.

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L-arginine (LA)-loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen (1 O2 ) and NO gas at tumor sites, respectively. Interestingly, 1 O2 from US-excited BMT can promote the oxidation of LA to produce more NO. The high concentration of 1 O2 and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double-strand breaks to induce cancer cell apoptosis ultimately. The US-triggered BMT@LA "nanovaccine" combining with immune checkpoint inhibitor PD-L1 antibody (αPD-L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA-based "nanovaccine" combining with αPD-L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.

An application of the 2018 Banff Classification for BK polyomavirus-associated nephropathy in renal transplantation.

BACKGROUND: There is still a lack of a recognized morphological classification of BK viral nephropathy (BKVN) which can better reflect the clinical manifestations and prognosis. METHODS: We retrospectively analyzed the data of 53 patients with BKVN in our center from January 2011 to December 2018 and evaluated the new Banff 2018 classifications' predictive value for the graft prognosis. RESULTS: The period between transplantation and BKVN diagnosis lasted for 10.3 months (IQR, 5.3-21.9 months). The main reason (92.5%) for puncture was the increase of blood serum creatinine. Of the 53 patients diagnosed with BKVN, 100% were positive for urinary BK virus-DNA, and the viral load was 1.4 × 108  copies/mL (IQR, 3.7 × 104 -1.3 × 1011  copies/mL); 75.5% were positive for blood BK virus-DNA, and the viral load was 3.3 × 104  copies/mL (IQR, 0-2.8 × 107  copies/mL). There were five cases in class 1, 31 cases in class 2, and 17 cases in class 3; the viral load of urine BK was 3.3 × 108 , 1.4 × 108 , and 6.3 × 107  copies/mL (P > .05); the viral load of blood BK was 3.3 × 104 , 3.3 × 104 , and 3.3 × 104  copies/mL (P > .05); the 1-year graft survival rates were 100%, 90.3%, and 52.9%, respectively (P < .05). CONCLUSION: BKVN mostly occurs within 1 year after transplantation. There is no correlation between BK virus load in hematuria and pathological damage at the time of diagnosis. The 2018 Banff Classification for BKVN can better indicate the prognosis of graft.

Rapid on-site evaluation of touch imprints of biopsies improves the diagnostic yield of transbronchial biopsy for endoscopically nonvisible malignancy: a retrospective study.

OBJECTIVE: Rapid on-site evaluation has long been used for transbronchial needle aspiration or fine-needle aspiration to evaluate the adequacy of biopsy materials for the diagnosis of peripheral lung lesions. However, research on rapid on-site evaluation combined with transbronchial forceps biopsy in the diagnosis of lung carcinoma is rarely reported. Therefore, we aimed to investigate the value of rapid on-site evaluation during transbronchial forceps biopsy for endoscopically visible (tumor, infiltrative and necrotic) or nonvisible (compressive, nonspecific and normal) malignancy. METHODS: A retrospective analysis was performed between January 2015 and January 2019 in Taihe Hospital with 1216 lung cancer patients who underwent bronchoscopy procedures, and these patients were allocated into the rapid on-site evaluation group and non-rapid on-site evaluation group, depending on the timing of the procedure. According to endoscopic features, bronchoscopic appearance was described as endoscopically visible malignancy (tumor, infiltrative and necrotic) and endoscopically nonvisible malignancy (compressive, nonspecific and normal). The diagnostic yield was compared, and the concordance between the rapid on-site evaluation results and the final histology was analyzed. RESULTS: There was a statistically significant difference in the diagnostic yield between the rapid on-site evaluation and non-rapid on-site evaluation groups for endoscopically nonvisible malignancy (74.3% vs. 51.7%, P < 0.05). However, we found no significant improvement in terms of diagnostic yield for endoscopically visible malignancy (95.2% vs. 91.2%, P > 0.05). The rapid on-site evaluation results showed high-level concordance with histology in the diagnosis of squamous cell carcinoma, adenocarcinoma and small cell carcinoma, with kappa values of 0.749 (P < 0.05), 0.728 (P < 0.05) and 0.940 (P < 0.05), respectively. CONCLUSIONS: The findings demonstrated that the diagnostic yield of transbronchial biopsy for endoscopically nonvisible malignancy (compressive, nonspecific and normal) was significantly improved when rapid on-site evaluation was implemented. In addition, the rapid on-site evaluation results had high-level concordance with the final histological diagnosis.