Perovskite solar cells based on screen-printed thin films.

One potential advantage of perovskite solar cells (PSCs) is the ability to solution process the precursors and deposit films from solution1,2. At present, spin coating, blade coating, spray coating, inkjet printing and slot-die printing have been investigated to deposit hybrid perovskite thin films3-6. Here we expand the range of deposition methods to include screen-printing, enabled by a stable and viscosity-adjustable (40-44,000 cP) perovskite ink made from a methylammonium acetate ionic liquid solvent. We demonstrate control over perovskite thin-film thickness (from about 120 nm to about 1,200 nm), area (from 0.5 × 0.5 cm2 to 5 × 5 cm2) and patterning on different substrates. Printing rates in excess of 20 cm s-1 and close to 100% ink use were achieved. Using this deposition method in ambient air and regardless of humidity, we obtained the best efficiencies of 20.52% (0.05 cm2) and 18.12% (1 cm2) compared with 20.13% and 12.52%, respectively, for the spin-coated thin films in normal devices with thermally evaporated metal electrodes. Most notably, fully screen-printing devices with a single machine in ambient air have been successfully explored. The corresponding photovoltaic cells exhibit high efficiencies of 14.98%, 13.53% and 11.80% on 0.05-cm2, 1.00-cm2 and 16.37-cm2 (small-module) areas, respectively, along with 96.75% of the initial efficiency retained over 300 h of operation at maximum power point.

Metallothionein Alleviates Glutathione Depletion-Induced Oxidative Cardiomyopathy through CISD1-Dependent Regulation of Ferroptosis in Murine Hearts.

This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. Wild-type and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mmol/L in drinking water) for 14 days before assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies, including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca2+ handling, sarcoplasmic reticulum Ca2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis, and apoptosis. Metallothionein itself did not affect myocardial morphology and function, although it mitigated BSO-provoked myocardial anomalies, loss of mitochondrial integrity and energy, and ferroptosis. Immunoblotting revealed down-regulated sarco(endo)plasmic reticulum Ca2+-ATPase 2a, glutathione peroxidase 4, ferroptosis-suppressing CDGSH iron-sulfur domain 1 (CISD1), and mitochondrial regulating glycogen synthase kinase-3ß phosphorylation with elevated p53, myosin heavy chain-ß isozyme, IκB phosphorylation, and solute carrier family 7 member 11 (SLC7A11) as well as unchanged SLC39A1, SLC1A5, and ferroptosis-suppressing protein 1 following BSO challenge, all of which, except glutamine transporter SLC7A11 and p53, were abrogated by metallothionein. Inhibition of CISD1 using pioglitazone nullified GSH-offered benefit against BSO-induced cardiomyocyte ferroptosis and contractile and intracellular Ca2+ derangement. Taken together, these findings support a regulatory modality for CISD1 in the impedance of ferroptosis in metallothionein-offered protection against GSH depletion-evoked cardiac aberration.

Computer-Aided Multiphoton Microscopy Diagnosis of 5 Different Primary Architecture Subtypes of Meningiomas.

Meningiomas rank among the most common intracranial tumors, and surgery stands as the primary treatment modality for meningiomas. The precise subtyping and diagnosis of meningiomas, both before and during surgery, play a pivotal role in enabling neurosurgeons choose the optimal surgical program. In this study, we utilized multiphoton microscopy (MPM) based on 2-photon excited fluorescence and second-harmonic generation to identify 5 common meningioma subtypes. The morphological features of these subtypes were depicted using the MPM multichannel mode. Additionally, we developed 2 distinct programs to quantify collagen content and blood vessel density. Furthermore, the lambda mode of the MPM characterized architectural and spectral features, from which 3 quantitative indicators were extracted. Moreover, we employed machine learning to differentiate meningioma subtypes automatically, achieving high classification accuracy. These findings demonstrate the potential of MPM as a noninvasive diagnostic tool for meningioma subtyping and diagnosis, offering improved accuracy and resolution compared with traditional methods.

Improving the diagnosis of ductal carcinoma in situ with microinvasion without immunohistochemistry: An innovative method with H&E-stained and multiphoton microscopy images.

Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).

TMNP: a transcriptome-based multi-scale network pharmacology platform for herbal medicine.

One of the most difficult problems that hinder the development and application of herbal medicine is how to illuminate the global effects of herbs on the human body. Currently, the chemo-centric network pharmacology methodology regards herbs as a mixture of chemical ingredients and constructs the 'herb-compound-target-disease' connections based on bioinformatics methods, to explore the pharmacological effects of herbal medicine. However, this approach is severely affected by the complexity of the herbal composition. Alternatively, gene-expression profiles induced by herbal treatment reflect the overall biological effects of herbs and are suitable for studying the global effects of herbal medicine. Here, we develop an online transcriptome-based multi-scale network pharmacology platform (TMNP) for exploring the global effects of herbal medicine. Firstly, we build specific functional gene signatures for different biological scales from molecular to higher tissue levels. Then, specific algorithms are designed to measure the correlations of transcriptional profiles and types of gene signatures. Finally, TMNP uses pharmacotranscriptomics of herbal medicine as input and builds associations between herbs and different biological scales to explore the multi-scale effects of herb medicine. We applied TMNP to a single herb Astragalus membranaceus and Xuesaitong injection to demonstrate the power to reveal the multi-scale effects of herbal medicine. TMNP integrating herbal medicine and multiple biological scales into the same framework, will greatly extend the conventional network pharmacology model centering on the chemical components, and provide a window for systematically observing the complex interactions between herbal medicine and the human body. TMNP is available at http://www.bcxnfz.top/TMNP.

Prognostic significance of collagen signatures in pancreatic ductal adenocarcinoma obtained from second-harmonic generation imaging.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. METHODS: Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. RESULTS: SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. CONCLUSIONS: SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.

Exploration of the relationship between tumor-infiltrating lymphocyte score and histological grade in breast cancer.

BACKGROUND: The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients. METHODS: In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs. RESULTS: Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648-3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3. CONCLUSION: Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.

Multi-omics approaches for the understanding of therapeutic mechanism for Huang-Qi-Long-Dan Granule against ischemic stroke.

After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.

MicrobeTCM: A comprehensive platform for the interactions of microbiota and traditional Chinese medicine.

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com.

Synthesis of (Furyl)Methyl Disulfides via Tandem Reaction of Conjugated Ene-Yne-Ketones with Acetyl-Masked Disulfide Nucleophiles.

In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.

Transition-Metal-Free Disulfuration of Amides with Trisulfide Dioxides via Formation of Unaccessible S-S-N Bonds.

Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N-disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

First report of Dactylonectria pauciseptata causing root rot on Eucalyptus cinerea in China.

Eucalyptus cinerea is an evergreen tree in the Myrtaceae. It is native to southern and eastern New South Wales and northern and eastern Victoria, Australia. It was introduced into China in the 1980s (Silva et al. 2011). Because of its unique shape, flexible stems, and rapid growth characteristics, it is widely used in the pulp industry and in decorative materials such as flower bouquets. In July 2022, 5- to 10-year-old E. cinerea showing symptoms of dehydration, withering and yellowing leaves, were found in forests and nurseries in Kunming and Songming, China. More than 37% of the trees showed these symptoms at each location, and disease severity was about 30%. Sixty symptomatic plants were collected from five tree nurseries. Diseased roots with 2-cm-long lesions were soaked in 75% ethanol for 15 s, 0.1% mercuric chloride for 2 min, rinsed with sterilized water, and placed on potato dextrose agar (PDA) at 25℃ for 3 days. Thirty samples were plated, and 21 isolates (YJLGF01 to YJLGF21) obtained, 11 strains with similar colony morphology (including representative strains YJLGF03 to YJLGF05). Three isolates (YJLGF03 to YJLGF05) were obtained by single-spore purification. On PDA, the colonies were circular with fluffy white to light yellow mycelium; the underside was yellowish brown. Conidiophores were bifurcated, with macroconidia borne terminally. The macroconidia were cylindrical with rounded, blunt ends, yellow to transparent, 1 to 3 septate (22.5 to 47.6 × 4.5 to 7.1 µm); microconidia were 0 to 1 septate (12.5 to 19.6 × 4.7 to 6.4 µm). Chlamydospores were spherical, rosary-like, and light yellow. Morphological characteristics were consistent with published descriptions of Dactylonectria pauciseptata (Piperkova et al. 2017). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1- alpha (ef1-α) gene, and the beta-tubulin 2 (ß-tub2) gene were amplified and sequenced (ITS accessions OR735053, OR735054, OR735055; ß-tub2 accessios OR757447, OR757448, OR757449; ef1-α accessions OR757450, OR757451, OR757451) using published primers (White et al. 1990; Carbone et al. 1999). A phylogenetic tree was developed by Maximum Parsimony (MP) and Maximum Likelihood (ML) methods. These three isolates fell into the D. pauciseptata clade and were distinguished clearly from other species. Pathogenicity tests were performed using the same three isolates. Each isolate was cultured on PDA, and then subcultured in V8 juice broth on an orbital shaker at 180 RPM for 5 days. Conidia were collected by centrifugation at 6,000 RPM for 5 min, and then resuspended in sterilized distilled water (1×106 conidia/ml). Injured roots of one-year-old E. cinerea were soaked in the spore suspension for 1 h before being transplanted in sterile vermiculite. The plants were incubated at 25℃ with a 12 h photoperiod and 90% humidity. Five plants were inoculated as a group for each treatment and the entire experiment was completed three times. Among the inoculated plants, the incidence of disease development was 100%. A small sot appeared after 4 days, with a water-soaked lesion appearing and gradually expanding during days 5 to 7. After 10 days symptoms of root necrosis were similar to the those observed in the nursery, and aboveground plant parts had yellow, withering leaves and defoliation after 10 to 15 days. Control plants treated with sterile water showed no disease symptoms. The three strains were successfully reisolated from inoculated seedlings and confirmed them using DNA sequencing. No isolates were obtained from the control plants, thus fulfilling Koch's postulates. Dactylonectria pauciseptata was first reported from necrotic tissue of infected grape roots (Schroers et al. 2008). So far, it has been reported in Turkey, Canada, Brazil, Italy, and other countries (Erper et al. 2013; Úrbez-Torres et al. 2014; Santos et al. 2014). Based on our results, E. cinerea is a new host plant of D. pauciseptata in China. This disease is a threat to the nursery production of E. cinerea, potentially leading to a reduction in yields and economic losses.

Leakage Benchmarking for Universal Gate Sets.

Errors are common issues in quantum computing platforms, among which leakage is one of the most-challenging to address. This is because leakage, i.e., the loss of information stored in the computational subspace to undesired subspaces in a larger Hilbert space, is more difficult to detect and correct than errors that preserve the computational subspace. As a result, leakage presents a significant obstacle to the development of fault-tolerant quantum computation. In this paper, we propose an efficient and accurate benchmarking framework called leakage randomized benchmarking (LRB), for measuring leakage rates on multi-qubit quantum systems. Our approach is more insensitive to state preparation and measurement (SPAM) noise than existing leakage benchmarking protocols, requires fewer assumptions about the gate set itself, and can be used to benchmark multi-qubit leakages, which has not been achieved previously. We also extended the LRB protocol to an interleaved variant called interleaved LRB (iLRB), which can benchmark the average leakage rate of generic n-site quantum gates with reasonable noise assumptions. We demonstrate the iLRB protocol on benchmarking generic two-qubit gates realized using flux tuning and analyzed the behavior of iLRB under corresponding leakage models. Our numerical experiments showed good agreement with the theoretical estimations, indicating the feasibility of both the LRB and iLRB protocols.

Quantitative Assessment of Hepatic Steatosis Using Label-Free Multiphoton Imaging and Customized Image Processing Program.

Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic generation and 2-photon excited fluorescence, was used to label-free image the samples of nonalcoholic fatty liver. Imaging results confirm that multiphoton microscopy is capable of directly visualizing important pathologic features such as normal hepatocytes, hepatic steatosis, Mallory bodies, necrosis, inflammation, collagen deposition, microvessel, and so on and is a reliable auxiliary tool for the diagnosis of nonalcoholic fatty liver disease. Furthermore, we developed an image segmentation algorithm to simultaneously assess hepatic steatosis and fibrotic changes, and quantitative results reveal that there is a correlation between the degree of steatosis and collagen content. We also developed a feature extraction program to precisely display the spatial distribution of hepatocyte steatosis in tissues. These studies may be beneficial for a better clinical understanding of the process of steatosis as well as for exploring possible therapeutic targets.

The Antimalaria Drug Artesunate Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Activating AMPK and Nrf2/HO-1 Signaling Pathways.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide. Currently, vaccine strategies provide limited protection against PRRSV transmission, and no effective drug is commercially available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV pandemics. This study showed that artesunate (AS), one of the antimalarial drugs, potently suppressed PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs) at micromolar concentrations. Furthermore, we demonstrated that this suppression was closely associated with AS-activated AMPK (energy homeostasis) and Nrf2/HO-1 (inflammation) signaling pathways. AS treatment promoted p-AMPK, Nrf2, and HO-1 expression and, thus, inhibited PRRSV replication in Marc-145 and PAM cells in a time- and dose-dependent manner. These effects of AS were reversed when the AMPK or HO-1 gene was silenced by short interfering RNA. In addition, we demonstrated that AMPK works upstream of Nrf2/HO-1, as its activation by AS is AMPK dependent. Adenosine phosphate analysis showed that AS activates AMPK via improving the AMP/ADP-to-ATP ratio rather than direct interaction with AMPK. Altogether, our findings indicate that AS is a promising novel therapeutic for controlling PRRSV and that its anti-PRRSV mechanism, which involves the functional link between energy homeostasis and inflammation suppression pathways, may provide opportunities for developing novel antiviral agents. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) infections have continuously threatened the pork industry worldwide. Vaccination strategies provide very limited protection against PRRSV infection, and no effective drug is commercially available. We show that artesunate (AS), one of the antimalarial drugs, is a potent inhibitor against PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs). Furthermore, we demonstrate that AS inhibits PRRSV replication via activation of AMPK-dependent Nrf2/HO-1 signaling pathways, revealing a novel link between energy homeostasis (AMPK) and inflammation suppression (Nrf2/HO-1) during viral infection. Therefore, we believe that AS may be a promising novel therapeutics for controlling PRRSV, and its anti-PRRSV mechanism may provide a strategy to develop novel antiviral agents.

Screening and identification of 3-aryl-quinolin-2-one derivatives as antiviral agents against influenza A.

Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 µM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.

Quantum Instruction Set Design for Performance.

A quantum instruction set is where quantum hardware and software meet. We develop characterization and compilation techniques for non-Clifford gates to accurately evaluate its designs. Applying these techniques to our fluxonium processor, we show that replacing the iSWAP gate by its square root SQiSW leads to a significant performance boost at almost no cost. More precisely, on SQiSW we measure a gate fidelity of up to 99.72% and averaging at 99.31%, and realize Haar random two-qubit gates with an average fidelity of 96.38%. This is an average error reduction of 41% for the former and a 50% reduction for the latter compared to using iSWAP on the same processor.

Rapid and label-free detection of gastrointestinal stromal tumor via a combination of two-photon microscopy and imaging analysis.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is currently regarded as a potentially malignant tumor, and early diagnosis is the best way to improve its prognosis. Therefore, it will be meaningful to develop a new method for auxiliary diagnosis of this disease. METHODS: Here we try out a new means to detect GIST by combining two-photon imaging with automatic image processing strategy. RESULTS: Experimental results show that two-photon microscopy has the ability to label-freely identify the structural characteristics of GIST such as tumor cells, desmoplastic reaction, which are entirely different from those from gastric adenocarcinoma. Moreover, an image processing approach is used to extract eight collagen morphological features from tumor microenvironment and normal muscularis, and statistical analysis demonstrates that there are significant differences in three features-fiber area, density and cross-link density. The three morphological characteristics may be considered as optical imaging biomarkers to differentiate between normal and abnormal tissues. CONCLUSION: With continued improvement and refinement of this technology, we believe that two-photon microscopy will be an efficient surveillance tool for GIST and lead to better management of this disease.

The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.