Generative Quantum Machine Learning via Denoising Diffusion Probabilistic Models.

Deep generative models are key-enabling technology to computer vision, text generation, and large language models. Denoising diffusion probabilistic models (DDPMs) have recently gained much attention due to their ability to generate diverse and high-quality samples in many computer vision tasks, as well as to incorporate flexible model architectures and a relatively simple training scheme. Quantum generative models, empowered by entanglement and superposition, have brought new insight to learning classical and quantum data. Inspired by the classical counterpart, we propose the quantum denoising diffusion probabilistic model (QuDDPM) to enable efficiently trainable generative learning of quantum data. QuDDPM adopts sufficient layers of circuits to guarantee expressivity, while it introduces multiple intermediate training tasks as interpolation between the target distribution and noise to avoid barren plateau and guarantee efficient training. We provide bounds on the learning error and demonstrate QuDDPM's capability in learning correlated quantum noise model, quantum many-body phases, and topological structure of quantum data. The results provide a paradigm for versatile and efficient quantum generative learning.

4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3.

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1-12 showed cytotoxicity to tumor cell lines with IC50 values in the range of 1.76-49.13 µM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.

A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase.

The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC50 values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC50 > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs.

Dapoxetine, a Selective Serotonin Reuptake Inhibitor, Suppresses Zika Virus Infection In Vitro.

Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC50 values ranging from 4.20 µM to 12.6 µM) and negligible cytotoxicity (CC50 > 50 µM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection.

Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.

Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus Didymella sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4+ T and CD8+ T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.

Effect of the optical power factors on the laser-linewidth measurements.

In this paper, the effects of optical power factors like laser power, the powers of the laser beams in the two arms of the optical system, and the power of the photodetector on laser-linewidth measurements are studied. From the experiments, it can be found that when the average optical input power for the photodetector is about 50% of its linear saturation power, the measured laser line width is a minimum. When the optical powers of the laser beams in the two arms are equal in short-delay self-homodyne system, the measured laser line width is narrowest. In the low output power range of the laser, its line width decreases with the increase in optical power. By comparing experiments, it can also be clear that the conventional measurement method is seriously affected by different noise types, which causes the measured line width to become wider and not change even if the laser linewidth changes. However, based on the short-delay coherent envelope method, the measured coherent envelope changes significantly when the laser line width changes slightly, and its corresponding laser-linewidth values are also clearly visible. It confirms the low noise and high resolution of the short-delay self-homodyne coherent-envelope laser-measurement method. The outcomes of this study can provide helpful information for precision ultra-narrow laser-linewidth measurements.

Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents.

The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC50 value from 1.33 µM to 5.72 µM) with low cytotoxicity (CC50＞50 µM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (Ifnar1-/-), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.

Compact Vernier sensor with an all-fiber reflective scheme for simultaneous measurements of temperature and strain.

We propose an all-fiber reflective sensing scheme to simultaneously measure temperature and strain. A length of polarization-maintaining fiber serves as the sensing element, and a piece of hollow-core fiber assists with introducing Vernier effect. Both theoretical deductions and simulative studies have demonstrated the feasibility of the proposed Vernier sensor. Experimental results have shown that the sensor can deliver sensitivities of -88.73 nm/°C and 1.61 nm/µÎµ for temperature and strain, respectively. Further, Both theoretical analyses and experimental results have suggested the capability of simultaneous measurement for such a sensor. Significantly, the proposed Vernier sensor not only presents high sensitivities, but also exhibits a simple structure, compact size and light weight, as well as demonstrates ease of fabrication and hence high repeatability, thus holding great promise for widespread applications in daily life and industry world.

Repurposing of Doramectin as a New Anti-Zika Virus Agent.

Zika virus (ZIKV), belonging to the Flavivirus family and mainly transmitted by mosquitoes, causes a variety of adverse outcomes, including Guillain-Barré syndrome, microcephaly, and meningoencephalitis. However, there are no approved vaccines or drugs available for ZIKV. The discovery and research on drugs for ZIKV are still essential. In this study, we identified doramectin, an approved veterinary antiparasitic drug, as a novel anti-ZIKV agent (EC50 value from 0.85 µM to 3.00 µM) with low cytotoxicity (CC50 > 50 µM) in multiple cellular models. The expression of ZIKV proteins also decreased significantly under the treatment of doramectin. Further study showed that doramectin directly interacted with the key enzyme for ZIKV genome replication, RNA-dependent RNA polymerase (RdRp), with a stronger affinity (Kd = 16.9 µM), which may be related to the effect on ZIKV replication. These results suggested that doramectin might serve as a promising drug candidate for anti-ZIKV.

A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway.

As a traditional Tibetan medicine in China, Meconopsis grandis Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in Meconopsis grandis Prain and its pharmacodynamic mechanisms have scarcely been reported. We isolated a meroterpenoid named D1399 from Meconopsis grandis Prain endophytic fungi with strong antitumor activity. The structure analysis showed that D1399 is an alkaloid containing a 13-membered macrocyclic structure. The IC50 of D1399 for human lung cancer cells' viability ranged from 0.88 to 2.45 µM. Furthermore, we utilized TUNEL assay and western blotting to investigate the antitumor effectiveness of D1399. The results have shown that D1399 induced the apoptosis of lung cancer cells on the extrinsic and intrinsic pathways by boosting ROS generation and repressing AKT activity. In the mouse xenograft model, the average tumor weight with 30 mg·kg-1 D1399 treatment exhibited 73.19% inhibition compared with the untreated control, without affecting body weight loss. Above all, for the first time, our study provides a possible mechanism for the antitumor activity of D1399 in vitro and in vivo as a natural product from Tibetan medicine with Meconopsis grandis Prain, which may be a potentially promising antitumor drug candidate.

Prevalence of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China.

PURPOSE: This study aimed to explore the prevalence and distribution of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China. METHODS: A multi-stage, group-matching random sampling method was adopted with 2579 elderly participants (≥ 60 years old) who were interviewed from January to May 2019. Preliminary screening was conducted using the scale by trained psychiatric nurses, followed by a diagnostic interview during the second stage using Chinese Version of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorder by trained psychiatrists. RESULTS: A total of 2561 participants were included in this study with complete data. The weighted lifetime prevalence of all mental disorders in the elderly was 16.2% (95% CI 15.3-17.1), and the weighted 12-month prevalence was 15.2% (95% CI 13.4-17.0). Depressive disorders, anxiety disorders, substance-related and addictive disorders were the most common mental disorders. The 12-month prevalence of all mental disorders were significantly higher in the elderly living alone, with chronic somatic disease, and being poor (P < 0.05). The 12-month prevalence of posttraumatic stress disorder (PTSD) was significantly higher in the elderly in extremely severely earthquake-affected areas (P < 0.001). CONCLUSION: The results of this study show that mental health status of the elderly in Ya'an area differ by socio-economic development, geographical location, and natural disasters. The social and economic development characteristics, the impact of major natural disasters (e.g., earthquakes), and population characteristics should be combined to formulate strategies and interventions to promote the mental health of the elderly.

Manipulation of Elastic Instability of Viscoelastic Fluid in a Rhombus Cross Microchannel.

This paper reports the manipulation of elastic instability of the viscoelastic fluid in a rhombus cross microchannel (RCM) structure. The bistable instability and unsteady instability of the flow is firstly demonstrated in a standard cross microchannel (SCM) for reference. We then keep the bi-stable instability over a much wider injection rate range in the RCM, which is attributed to the stabilizing effect of the rhombus structure. A semi-bistable instability was also established in the RCM at a high enough injection rate. In addition, the unsteady elastic instability is realized in the RCM through an asymmetric injection rate condition.

Precise laser linewidth measurement by feature extraction with short-delay self-homodyne.

We propose a precision measurement method of laser linewidth based on short-delay self-homodyne, using the second peak-valley difference (SPVD) feature of the coherent power spectrum to fit laser linewidth. The SPVD model of the self-homodyne coherent envelope spectrum was established. One-to-one correspondence among the values of SPVD, the delay length, and the laser linewidth was determined theoretically and through simulations, while the reliability and stability of the method was verified experimentally. By comparing the detected results, it is found that the fitted laser linewidth obtained by the self-homodyne system is closer to its true value than that obtained by the self-heterodyne system. Hence, the simpler structure of the short-delay self-homodyne coherent envelope laser linewidth measurement method proposed is expected to substitute the previous laser linewidth measurement method, including complex short-delay self-heterodyne coherent envelope laser linewidth measurement method and traditional self-homodyne/heterodyne laser linewidth measurement method, to achieve more precise laser linewidth value.

Numerical demonstration of low-reflective wire grid polarizers with a patterned Fe2O3 absorptive layer.

Absorptive polarizers are pivotal components for realizing a low ambient reflection in liquid crystal displays (LCDs) and organic light-emitting diodes (OLEDs). Different types of absorptive polarizers have been proposed. Nevertheless, the realization of compact and efficient absorptive polarizers remains challenging. Wire grid polarizers (WGPs) are a promising solution because of their high durability and relatively thin thickness. In this paper, two structures of absorptive-WGPs have been proposed and optimized at the target wavelength of 532 nm: one is based on a patterned F e 2 O 3/A l bi-layer on top of a S i O 2 substrate, and the second one builds on the first one by depositing a S i O 2 layer in the gaps of Al. The optimal solutions exhibit a reflectance less than 5%, a transmittance over 45%, and an extinction ratio over 40 dB. To evaluate the manufacturing feasibility, their sensitivity to the wire's dimensional parameters is investigated. Their great spectral performance and large acceptance angles demonstrate that such polarizers have the potential to significantly promote the development of current display technologies.

The impacts of COVID-19 outbreak on mental health in general population in different areas in China.

BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.

Effect of Oxidative Stress on Diaphragm Dysfunction and Exercise Intervention in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) can cause extrapulmonary injury such as diaphragm dysfunction. Oxidative stress is one of the main factors causing diaphragm dysfunction in COPD. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. Therefore, on the basis of the review of oxidative stress and the changes in diaphragm structure and function in COPD, this article analyzed the effects of exercise on oxidative stress and diaphragm dysfunction in COPD and explored the possible mechanism by which exercise improves oxidative stress. Studies have found that diaphragm dysfunction in COPD includes the decline of muscle strength, endurance, and activity. Oxidative stress mainly affects the structure and function of the diaphragm in COPD through protein oxidation, protease activation and calcium sensitivity reduction. The effects of exercise on oxidative stress level and diaphragm dysfunction may differ depending on the intensity, duration, and style of exercise. The mechanism of exercise on oxidative stress in the diaphragm of COPD may include improving antioxidant capacity, reducing oxidase activity and improving mitochondrial function.

Microfluid-based soft metasurface for tunable optical activity in THz wave.

Metasurfaces are usually planar structures and do not possess intrinsic chirality and therefore hardly generate optical activity. Here we realized a tunable optical activity in a terahertz wave through a microfluid-based soft metasurface. The meta-atom is a chiral structured microchannel made of soft polydimethylsiloxane and injected with the liquid metal Galinstan. A microfluid pressure system is bonded to the metasurface to reconfigure all meta-atoms simultaneously. By pumping glycerol liquid into the pressure system, the metasurface is deformed from a planar structure to a three dimensional one, which manifests intrinsic chirality for optical activity realization. By controlling the injected glycerol volume, a polarization rotation from 0°to 14° at 0.19 THz is demonstrated. The soft metasurface with tunable optical activity can be flexibly applied in various applications such as polarization microscopy, bio-detection and material analysis, etc.

An epidemiological survey of mental disorders 5 years after the Lushan earthquake in Ya'an, China.

PURPOSE: This study aimed to (1) explore the prevalence and relevant influencing factors of different mental disorders 5 years after the Lushan earthquake in Ya'an, China. METHODS: An epidemiological mental health survey was conducted to identify the prevalence of mental disorders in general population in Ya'an. A multi-stage, group-matching random sampling method was adopted. Face-to-face interviews were done with a two-stage design by trained interviewers and psychiatrists. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was used for the diagnosis. RESULTS: There were 8876 participants who were interviewed in this study. The total 12-month and lifetime prevalence of all mental disorders were 12.5% and 14.7%, respectively. There was a significant difference between males and females in the prevalence patterns of several mental disorders. Han ethnic group had higher prevalence of anxiety disorders (2.7%), and the Tibetan group had higher prevalence of alcohol-related disorders (5.0%). Logistic regression analysis showed that the areas severely affected by the earthquake had significantly higher prevalence of depressive disorders, and the extremely severe affected areas had significantly higher prevalence of trauma- and stressor-related disorders. CONCLUSION: Our findings show that the prevalence of a range of mental disorders 5 years after the earthquake in Ya'an are high, and the prevalence of depressive and trauma- and stressor-related disorders may be influenced differently by the various severity of earthquake impact. This study may be crucial for the health policy-making, cultural-specific mental health services and long-term mental recovery after the earthquake.

Unified approaches to assessing treatment effect of traditional Chinese medicine based on health profiles.

Two dissimilarity indices are introduced to measure the disharmony of a human body system by mimicking the population bioequivalence and the individual bioequivalence concepts. Hypotheses for the treatment effect of a traditional Chinese medicine are formulated based on the two indices and then tested under the proposed designs by reverting an approximate confidence upper bound. The proposed methods can also be used when a drug product has multiple components or a trial has multiple endpoints.

Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma.

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. METHODS: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL-1, ≥300 eosinophils·µL-1, ≥25 ppb fractional exhaled nitric oxide (F eNO), and both ≥150 eosinophils·µL-1 and ≥25 ppb F eNO, at baseline. RESULTS: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s-1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4-52) was significant (0.04 L·year-1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F eNO levels for most outcomes. CONCLUSIONS: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.