Opportunities for fundamental physics research with radioactive molecules.

Molecules containing short-lived, radioactive nuclei are uniquely positioned to enable a wide range of scientific discoveries in the areas of fundamental symmetries, astrophysics, nuclear structure, and chemistry. Recent advances in the ability to create, cool, and control complex molecules down to the quantum level, along with recent and upcoming advances in radioactive species production at several facilities around the world, create a compelling opportunity to coordinate and combine these efforts to bring precision measurement and control to molecules containing extreme nuclei. In this manuscript, we review the scientific case for studying radioactive molecules, discuss recent atomic, molecular, nuclear, astrophysical, and chemical advances which provide the foundation for their study, describe the facilities where these species are and will be produced, and provide an outlook for the future of this nascent field.

Effect of different reduction methods on Pd/Al2O3 for o-xylene oxidation at low temperature.

Pd/Al2O3 was pretreated by CO, H2 and NaBH4 reduction, respectively. The reduced catalysts were tested for o-xylene oxidation and characterized by power X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and temperature-programmed decomposition of palladium hydride (TPDH). The characterizations indicate the pretreatments lead to distinct Pd particle sizes and amount of surface activated oxygen species, which are responsible for the catalytic performance. Compared with H2 and NaBH4 reduction methods, CO reduction shows a strong interaction between Pd and Al2O3 with smaller Pd particle size and more surface activated oxygen. It exhibited excellent catalytic performance, complete oxidation of 50 ppmV o-xylene at 85°C with a WHSV of 60,000 mL/(g∙hr).

Development of an indirect ELISA to detect PEDV specific IgA antibody based on a PEDV epidemic strain.

BACKGROUND: Porcine epidemic diarrhea (PED), a swine epidemic disease caused by porcine epidemic diarrhea virus (PEDV), is characterized by severe watery diarrhea, vomiting, dehydration and high mortality in piglets, and has caused serious economic losses to the global porcine industry. The level of PEDV IgA antibody is a key marker to assess the extent of passive immunity of the resistance against PEDV infection. However, current commercial structure proteins-based kits for detection of PEDV antibody are not affordable, and those kits require complicated antigen preparation procedures, which cannot meet the scope of economic benefits of many large-scale pig companies in China. Therefore, there is an urgent need to develop an accurate, simple, and economical method for IgA detection in clinical samples. In this study, an indirect ELISA (i-ELISA) method was developed based on a purified PEDV epidemic strain (NH-TA2020). RESULTS: The results show that optimal working dilution ratios of PEDV antigen and HRP anti-swine IgA are at 1: 1000 and 1:15000 respectively. The sensitivity of this method is high with the maximum dilution of samples up to 1:160, and coefficients of variation (CV) of both the intra assays and inter assays were no more than 15%. In addition, the relative sensitivities of the i-ELISA were above 90% compared with values from commercial kits in both serum and oral fluid samples. CONCLUSIONS: Our results suggested that the i-ELISA developed in this study was an accurate, simple, and economical method for PEDV-IgA detection in clinical samples.

Chirality of Perylene Diimides: Design Strategies and Applications.

Chirality is a particularly important concept in nature and exists at all length scales, ranging from the molecular level to the supramolecular level. Over the last two decades, various design strategies have been developed to construct chiral materials based on perylene diimides (PDIs) and to mimic the chiral assembly process in biological systems, but applications of these chiral aggregates are still at an early stage. This Minireview summarizes recent progress in the synthesis and properties of chiral PDIs. The chirality in PDI-based materials can be generated by three different approaches: from the twisted planes of PDIs, the chiral substituents of PDIs, and the co-assembly of achiral PDIs and chiral guests. A comprehensive understanding of the applications of chiral PDIs as well as potential future developments is also provided.

Effects of different concentrations of metformin on osteoclast differentiation and apoptosis and its mechanism.

This study aimed to investigate the effect of metformin on osteoclast differentiation and apoptosis. Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6. High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.

Expressions of IL-12 and its receptors in patients with lumbar disc herniation and their relationship with clinical efficacy.

This study aimed to explore the expressions of interleukin-12 (IL-12) and its receptors IL-23R and IL12RB2 in patients with lumbar disc herniation (LDH) before and after treatment and their relationship with clinical efficacy. A total of 172 LDH patients undergoing surgical treatment in Wuhan Third Hospital, Tongren Hospital of Wuhan University were enrolled as the study group, and 170 healthy subjects as the control group. 5 mL of fasting venous blood was taken before surgery (T0), 1 d (T1), 3 d (T2), 5 d (T3) and 7 d (T4) after treatment respectively. The concentrations of IL-12, IL-23R and IL12RB2 in the two groups were detected, and the correlation between them and the treatment duration and clinical efficacy was analyzed. The study group showed significantly higher serum IL-12, IL-23R and IL12RB2 than the control group before treatment (P < 0.001). In the study group, IL-12, IL-23R and IL-12RB2 were the lowest at T4 (P < 0.001), followed by T3 (P < 0.001). There was no significant difference in IL-23R at T1 and T0 (P > 0.050), and in IL12RB2 at T1 and T2 (P > 0.050). Spearman rank correlation showed that IL-12, IL-23R, IL12RB2 were negatively correlated with treatment duration in the study group (P < 0.001), and were positively correlated with clinical efficacy (P < 0.001). In conclusion, the concentrations of serum IL-12, IL-23R and IL12RB2 in LDH patients are significantly higher than those in normal controls. Moreover, the concentrations are closely related to the rehabilitation of patients and are expected to become therapeutic targets for LDH.

miR-186-5p Functions as a Tumor Suppressor in Human Osteosarcoma by Targeting FOXK1.

BACKGROUND/AIMS: Aberrantly expressed miRNAs play a vital role in the development of some cancers, such as human osteosarcoma (OS). However, the detailed molecular mechanisms underlying miR-186-5p-involved osteosarcoma are unclear. METHODS: qRT-PCR and western blot analysis were employed to measure the expressions of miR-186-5p and forkhead box k1 (FOXK1). CCK-8 assay evaluated the effect of miR-186-5p and FOXK1 on cell proliferation. Transwell assay confirmed cell migration and invasion. Eventually, the dual-luciferase reporter assay validated 3'-untranslated region (3'-UTR) of FOXK1 as a direct target of miR-186-5p. RESULTS: Down-regulation of miR-186-5p was identified in OS tissues and cell lines, and negatively correlated with distant metastasis, Enneking stage and poor 5-year prognosis as well as the expression of forkhead box k1 (FOXK1) protein. Further assays demonstrated that miR-186-5p overexpression had inhibitory effects on in-vitro cell proliferation, cell cycle, and in-vivo tumor growth. miR-186-5p overexpression also inhibited the epithelial-tomesenchymal transition (EMT), migration and invasion of OS cells. Importantly, miR-186-5p directly targeted FOXK1 3'-UTR and negatively regulated its expression. Silencing of FOXK1 expression enhanced the inhibitory effects of miR-186-5p on OS cell proliferation, migration and invasion. CONCLUSION: These findings highlighted miR-186-5p as a tumor suppressor in the regulation of progression and metastatic potential of OS, and may benefit the development of therapies targeting miR-186-5p in patients with OS.

Inhibition of mitochondrial translation selectively targets osteosarcoma.

The unique dependence of cancer cells on mitochondrial metabolism has been exploited therapeutically in various cancers but not osteosarcoma. In this work, we demonstrate that inhibition of mitochondrial translation is effective and selective in targeting osteosarcoma. We firstly showed that tigecycline at pharmacological achievable concentrations inhibited growth and induced apoptosis of multiple osteosarcoma cell lines while sparing normal osteoblast cells. Similarly, tigecycline at effective doses that delayed osteosarcoma growth did not cause significant toxicity to mice. We next showed that tigecycline specifically inhibits mitochondrial translation, resulting in defective mitochondrial respiration in both osteosarcoma and normal osteoblast cells. We further confirm mitochondrial respiration as the target of tigecycline using three independent approaches. In addition, we demonstrate that compared to normal osteoblasts, osteosarcoma cells have higher mitochondrial biogenesis. We finally show that specific inhibition of mitochondrial translation via EF-Tu depletion produces the similar anti-osteosarcoma effects of tigecycline. Our work highlights the therapeutic value of targeting mitochondrial metabolism in osteosarcoma and tigecycline as a useful addition to the treatment of osteosarcoma.

Effect of indica pedigree on eating and cooking quality in rice backcross inbred lines of indica and japonica crosses.

Amylopectin is one of the major determinants of rice (Oryza sativa L.) grain quality, and a large difference in amylopectin is found between two subspecies: japonica and indica. However, the relationship among rice grain quality, indica/japonica genetic background, and amylopectin has not been clearly established. In this study, a series of backcross inbred lines derived from the cross between japonica (cv. Sasanishiki) and indica (cv. Habataki) were used to survey eating and cooking quality (ECQ), rapid visco analyzer (RVA) profiles, and the chain length distribution of amylopectin. The frequency of indica pedigree (Fi) was calculated to analyze the effects of Fi on grain quality and amylopectin. The results showed that the Sasanishiki cultivar was markedly enriched in chain length with DP6-15 and DP34-45 compared to the Habataki. DP34-45 strongly correlated to RVA characteristics, cooking quality, and prolamin content. The Fi also has significant correlations to RVA characteristics and ECQ, but only significantly negative correlation to DP34-45. Seven quantitative trait loci (QTLs) corresponding to amylopectin were mapped, of which three were in agreement with previous findings. The results of this study provide valuable information for amylopectin characteristics in the offspring derived from the subspecies cross, and the novel QTLs may provide new insights to the identification of minor starch synthesis-related genes.

A suitable sampling strategy for the detection of African swine fever virus in living and deceased pigs in the field: a retrospective study.

African swine fever (ASF) is a fatal disease that threatens the health status of the swine population and thus can impact the economic outcome of the global pig industry. Monitoring the ASF virus (ASFV) is of utmost concern to prevent and control its distribution. This study aims to identify a suitable sampling strategy for ASFV detection in living and deceased pigs under field conditions. A range of samples, comprising tissues obtained from deceased pigs, as well as serum and tonsil swab samples from live pigs, were gathered and subjected to detection using the qPCR method. The findings revealed that the mandibular lymph nodes demonstrated the highest viral loads among superficial tissues, thereby indicating their potential suitability for detecting ASFV in deceased pigs. Additionally, the correlations between virus loads in various tissues have demonstrated that tonsil swab samples are a viable specimen for monitoring live pigs, given the strong associations observed with other tissues. These findings indicated two dependable sample types for the detection of ASFV: mandibular lymph nodes for deceased pigs and tonsil swabs for live pigs, which supply some references for the development of efficacious preventive measures against ASFV.

Effects of flowering period on floral traits, pollinator behavior and seed production of David's mountain laurel (Sophora davidii).

Sophora davidii is a cross-pollinated plant with important ecological protection and medicinal value in China, but its seed yield is low due to backward and nonstandard production technology. Therefore, we divide the flowering period of Sophora davidii into initial, full and final flowering period, measuring the floral morphology, pollen viability, stigma receptivity, nectar volume and nectar concentration, foraging behavior of pollinators, fertilization physiology, seed yield and quality through field observation and indoor testing to explore whether the flowering period affects the floral traits, pollinator behavior and seed production of plants. Our results revealed that the nectar volume, nectar concentration, pollen viability and stigma receptivity at full flowering period were the highest. The single visit time and visit time per flower of Chinese honey bees were the longest in the full flowering period, while the number of transfer, visit frequency and number of touching stigma were the least. The visiting number of the bees was the most and the most active in the full flowering period. The bees pollination not only improved the pollen amount, germination rate, pollen tube length and the ovule number of S. davidii, but also their effect was the most obvious in full flowering period. The principal component analysis showed that pollination by Chinese honey bees during the whole flowering period of S. davidii was the best way to produce seeds. We can conclude that flowering period affects flower traits, foraging behavior of pollinators, seed yield and quality of S. davidii.

Comparison of characteristics of connective tissue disease-associated interstitial lung diseases, undifferentiated connective tissue disease-associated interstitial lung diseases, and idiopathic pulmonary fibrosis in Chinese Han population: a retrospective study.

Our study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2009 and December 2012 in West China Hospital, western China. Patients who met the criteria for ILD were included and were assigned to CTD-ILD, UCTD-ILD, or IPF group when they met the criteria for CTD, UCTD, or IPF, respectively. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. 203 patients were included, and all were Han nationality. CTD-ILD was identified in 31%, UCTD-ILD in 32%, and IPF in 37%. Gender and age differed among groups. Pulmonary symptoms were more common in IPF, while extrapulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Little significance was seen in HRCT images among three groups. A systematic evaluation of symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF.

Probing fundamental particles with molecules.

Molecular spectroscopy constrains the size of the electron's electric dipole moment.

Feature-guided attention network for medical image segmentation.

BACKGROUND: U-Net and its variations have achieved remarkable performances in medical image segmentation. However, they have two limitations. First, the shallow layer feature of the encoder always contains background noise. Second, semantic gaps exist between the features of the encoder and the decoder. Skip-connections directly connect the encoder to the decoder, which will lead to the fusion of semantically dissimilar feature maps. PURPOSE: To overcome these two limitations, this paper proposes a novel medical image segmentation algorithm, called feature-guided attention network, which consists of U-Net, the cross-level attention filtering module (CAFM), and the attention-guided upsampling module (AUM). METHODS: In the proposed method, the AUM and the CAFM were introduced into the U-Net, where the AUM learns to filter the background noise in the low-level feature map of the encoder and the CAFM tries to eliminate the semantic gap between the encoder and the decoder. Specifically, the AUM adopts a top-down pathway to use the high-level feature map so as to filter the background noise in the low-level feature map of the encoder. The AUM uses the encoder features to guide the upsampling of the corresponding decoder features, thus eliminating the semantic gap between them. Four medical image segmentation tasks, including coronary atherosclerotic plaque segmentation (Dataset A), retinal vessel segmentation (Dataset B), skin lesion segmentation (Dataset C), and multiclass retinal edema lesions segmentation (Dataset D), were used to validate the proposed method. RESULTS: For Dataset A, the proposed method achieved higher Intersection over Union (IoU) ( 67.91 ± 3.82 % $67.91\pm 3.82\%$ ), dice ( 79.39 ± 3.37 % $79.39\pm 3.37\%$ ), accuracy ( 98.39 ± 0.34 % $98.39\pm 0.34\%$ ), and sensitivity ( 85.10 ± 3.74 % $85.10\pm 3.74\%$ ) than the previous best method: CA-Net. For Dataset B, the proposed method achieved higher sensitivity (83.50%) and accuracy (97.55%) than the previous best method: SCS-Net. For Dataset C, the proposed method had highest IoU ( 83.47 ± 0.41 % $83.47\pm 0.41\%$ ) and dice ( 90.81 ± 0.34 % $90.81\pm 0.34\%$ ) than those of all compared previous methods. For Dataset D, the proposed method had highest dice (average: 81.53%; retina edema area [REA]: 83.78%; pigment epithelial detachment [PED] 77.13%), sensitivity (REA: 89.01%; SRF: 85.50%), specificity (REA: 99.35%; PED: 100.00), and accuracy (98.73%) among all compared previous networks. In addition, the number of parameters of the proposed method was 2.43 M, which is less than CA-Net (3.21 M) and CPF-Net (3.07 M). CONCLUSIONS: The proposed method demonstrated state-of-the-art performance, outperforming other top-notch medical image segmentation algorithms. The CAFM filtered the background noise in the low-level feature map of the encoder, while the AUM eliminated the semantic gap between the encoder and the decoder. Furthermore, the proposed method was of high computational efficiency.

Online Active Continual Learning for Robotic Lifelong Object Recognition.

In real-world applications, robotic systems collect vast amounts of new data from ever-changing environments over time. They need to continually interact and learn new knowledge from the external world to adapt to the environment. Particularly, lifelong object recognition in an online and interactive manner is a crucial and fundamental capability for robotic systems. To meet this realistic demand, in this article, we propose an online active continual learning (OACL) framework for robotic lifelong object recognition, in the scenario of both classes and domains changing with dynamic environments. First, to reduce the labeling cost as much as possible while maximizing the performance, a new online active learning (OAL) strategy is designed by taking both the uncertainty and diversity of samples into account to protect the information volume and distribution of data. In addition, to prevent catastrophic forgetting and reduce memory costs, a novel online continual learning (OCL) algorithm is proposed based on the deep feature semantic augmentation and a new loss-based deep model and replay buffer update, which can mitigate the class imbalance between the old and new classes and alleviate confusion between two similar classes. Moreover, the mistake bound of the proposed method is analyzed in theory. OACL allows robots to select the most representative new samples to query labels and continually learn new objects and new variants of previously learned objects from a nonindependent and identically distributed (i.i.d.) data stream without catastrophic forgetting. Extensive experiments conducted on real lifelong robotic vision datasets demonstrate that our algorithm, even trained with fewer labeled samples and replay exemplars, can achieve state-of-the-art performance on OCL tasks.

Evidence of aerosol transmission of African swine fever virus between two piggeries under field conditions: a case study.

African swine fever (ASF) is a devastating and economically significant infectious disease that has caused enormous losses in the commercial pig sector in China since 2018. The primary transmission routes of the African swine fever virus (ASFV), the causative agent of ASF, are direct pig-to-pig contact or indirect contact with virus-contaminated objects. While aerosol transmission of ASFV has been previously reported under experimental conditions, no reports have described it under field conditions. In this case study, aerosol-associated samples were collected over a monitoring period of 24 days in an ASFV-positive farm. A complete and clear chain of ASFV transmission through aerosols was observed: pigs in Room A on Day 0-aerosol in Room A on Day 6-dust of air outlets in Room A on Day 9-outdoor aerosols on Day 9-dust of air inlets in Room B on Day 15-aerosols/pigs in Room B on Day 21. Furthermore, a fluorescent powder experiment confirmed the transmission of dust from Room A to Room B. This study represents the first report providing evidence of aerosol transmission of ASFV under field conditions. Further research is needed to study the laws of aerosol transmission in ASFV and develop effective strategies such as air filtration or disinfection to create a low-risk environment with fresh air for pig herds.

Complete pathological response and negative postoperative ctDNA were not predictive of discontinuation of adjuvant crizotinib therapy in a patient with locally advanced MET ex14 skipping mutation-positive non-small cell lung cancer: a case report.

Neoadjuvant targeted therapy is an alternative treatment for locally advanced non-small cell lung cancer (NSCLC) patients with driver gene mutation. MET ex14 mutation is considered a driver gene, and crizotinib is the first oral tyrosine kinase inhibitor (TKI) for metastatic MET ex14 mutation-positive NSCLC patients. Here, we reported a case of a locally advanced NSCLC patient harboring MET ex14 mutation who achieved pathological complete response following neoadjuvant crizotinib therapy but developed rapid metastasis due to discontinuation of short-term postoperative adjuvant crizotinib therapy. Although no driver gene mutation was found via next-generation sequencing (NGS) with blood samples before discontinuation of adjuvant crizotinib, the patient was given crizotinib rechallenge. Fortunately, the patient achieved durable complete response. This suggested that neither pathological complete response nor negative circulating tumor DNA (ctDNA) could be an effective predictor for discontinuation of adjuvant targeted therapy. This case report demonstrated the potential of crizotinib as neoadjuvant therapy in MET ex14 mutation-positive NSCLC patients as well as the importance of long-term postoperative therapy even with negative ctDNA in blood.

Infection characteristics of porcine circovirus type 2 in different herds from intensive farms in China, 2022.

Introduction: Porcine circovirus type 2 (PCV2) is the primary etiological agent of porcine circovirus diseases (PCVD), which are widespread in most pig herds, causing huge economic losses in the global pig industry. Therefore, it is critical to assess the infection characteristics of PCV2 in different swine herds to develop effective strategies against PCVD. Methods: In this study, routine diagnostic and monitoring protocols were used to collect 12,714 samples from intensive farms in China, and PCV2 was tested for by qPCR to determine positivity rates and viral loads in samples from different herds and materials. Results: PCV2 was found to be prevalent throughout China, and fattening farms had higher positivity rates than breeding farms. The PCV2 positivity rates in breeding farms in Southern China were higher than those in Northern China. Growing-finishing pigs demonstrated the highest positivity rate in the tested samples, while pre-weaning piglets and adult sows had the lowest. Meanwhile, samples with viral loads exceeding 106 copies/mL in growing-finishing pigs had 27.2% positivity, compared to 1.9% and 3.3% in sows and piglets, respectively. The results of the viral loads in the serum samples followed a similar trend. Discussion: The findings reveal that PCV2 circulates in different herds from intensive farms, with positivity increasing from pre-weaning to growing-finishing herds. It is urgent to develop effective strategies to reduce PCV2 positivity in growing-finishing herds and prevent viral circulation among pigs.

Generalized propensity score for estimating the average treatment effect of multiple treatments.

The propensity score method is widely used in clinical studies to estimate the effect of a treatment with two levels on patient's outcomes. However, due to the complexity of many diseases, an effective treatment often involves multiple components. For example, in the practice of Traditional Chinese Medicine (TCM), an effective treatment may include multiple components, e.g. Chinese herbs, acupuncture, and massage therapy. In clinical trials involving TCM, patients could be randomly assigned to either the treatment or control group, but they or their doctors may make different choices about which treatment component to use. As a result, treatment components are not randomly assigned. Rosenbaum and Rubin proposed the propensity score method for binary treatments, and Imbens extended their work to multiple treatments. These authors defined the generalized propensity score as the conditional probability of receiving a particular level of the treatment given the pre-treatment variables. In the present work, we adopted this approach and developed a statistical methodology based on the generalized propensity score in order to estimate treatment effects in the case of multiple treatments. Two methods were discussed and compared: propensity score regression adjustment and propensity score weighting. We used these methods to assess the relative effectiveness of individual treatments in the multiple-treatment IMPACT clinical trial. The results reveal that both methods perform well when the sample size is moderate or large.

Activity scheduling as a core component of effective care management for late-life depression.

BACKGROUND: Activity scheduling is an established component of evidenced-based treatment for late-life depression in primary care. We examined participant records from the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial to identify activity scheduling strategies used in the context of successful depression care management (CM), associations of activity scheduling with self-reported activity engagement, and depression outcomes. METHODS: This study used observational mixed methods analysis of 4335 CM session notes from 597 participants in the intervention arm of the IMPACT trial. Grounded theory was used to identify 17 distinct activity categories from CM notes. Logistic regression was used to evaluate associations between activity scheduling, activity engagement, and depression outcomes at 12 months. All relevant institutional review boards approved the research protocol. RESULTS: Seventeen distinct activity categories were generated. Most patients worked on at least one social and one solitary activity during their course of treatment. Common activity categories included physical activity (32%), medication management (22%), active-non-physical (19%), and passive (14%) activities. We found significant, positive associations between activity scheduling, self-reported engagement in activities at 12 months, and depression outcomes at 12 months. CONCLUSION: Older primary care patients in CM for depression worked on a wide range of activities. Consistent with depression theory that has placed emphasis on social activities, the data indicate a benefit for intentional social engagement versus passive social and solitary activities. Care managers should encourage patients to balance instrumental activities (e.g., attending to medical problems) with social activities targeting direct interpersonal engagement.