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Organoids are expected to function as effective human organ models for precision cancer studies and drug development. Currently, primary tissue-derived organoids, termed non-engineered organoids (NEOs), are produced by manual pipetting or liquid handling that compromises organoid-organoid homogeneity and organoid-tissue consistency. Droplet-based microfluidics enables automated organoid production with high organoid-organoid homogeneity, organoid-tissue consistency, and a significantly improved production spectrum. It takes advantage of droplet-encapsulation of defined populations of cells and droplet-rendered microstructures that guide cell self-organization. Herein, we studied the droplet-engineered organoids (DEOs), derived from mouse liver tissues and human liver tumors, by using transcriptional analysis and cellular deconvolution on bulk RNA-seq data. The characteristics of DEOs are compared with the parental liver tissues (or tumors) and NEOs. The DEOs are proven higher reproducibility and consistency with the parental tissues, have a high production spectrum and shortened modeling time, and possess inter-organoid homogeneity and inter-tumor cell heterogeneity.

BackgroundThe Systemic Inflammatory Response Index (SIRI) is a promising inflammatory marker; however, the relationship between SIRI and latent tuberculosis infection (LTBI), as well as its association with mortality rates, remains unclear. The present study aimed to explore the associations of the SIRI with LTBI and all-cause mortality.MethodsWe conducted a prospective cohort study using data from National Health and Nutrition Examination Survey (NHANES) cycles from 2011 to 2012. We explored the association between SIRI and LTBI prevalence using Multiple logistic regression models. We used Multivariate Cox proportional hazards model to analyze the association between SIRI and all-cause mortality. In addition, Kaplan-Meier curves, restricted cubic splines (RCS), stratified analysis, and interaction tests were performed.ResultsThe study included a total of 4,983 adults who participated in NHANES 2011-2012. The mean follow-up period was 92.35 ± 16.82 months, and there were 525 deaths, representing a mortality rate of 10.54%. The occurrence of LTBI is significantly associated with low SIRI levels(OR=0.76, 95% CI: 0.66-0.89), after adjusting for confounders. Among LTBI patients, elevated SIRI levels are significantly correlated with an increased risk of all-cause mortality (adjusted HR = 1.48, 95% CI: 1.01-2.15). RCS revealed a linear relationship between SIRI and all-cause mortality in patients with LTBI (P =0.059[overall] and P = 0.391 [Nonlinear]). Furthermore, within the LTBI population, the area under the curve (AUC) of SIRI for all-cause mortality are 0.731 (1-year), 0.640 (3-year), and 0.634 (5-year).ConclusionThe findings of this study indicate that elevated SIRI levels are independently associated with an increased risk of all-cause mortality in patients with LTBI. Notably, SIRI was significantly inversely associated with the incidence of LTBI. Therefore, SIRI may serve as an effective tool for risk stratification in adults with LTBI in the United States. Further research is needed to elucidate the underlying mechanisms and to explore any therapeutic implications of these findings.

Background: Financial toxicity (FT) is a global challenge for breast cancer patients due to high costs of care. Financial navigation is a promising intervention to alleviate FT, but evidence remains limited, especially within the Chinese healthcare system. To assess the feasibility, acceptability, and preliminary effects of a financial navigation program among breast cancer patients in China. Methods: In this single-center, single-blinded pilot randomized controlled trial, a financial navigation program comprising needs assessment, cost-related health education, resource/service referral, and personalized counseling was evaluated. Feasibility was assessed through recruitment, attrition, and adherence rates. Acceptability was measured via participant satisfaction surveys and semi-structured interviews. Preliminary effects were evaluated through cost-related health literacy and three domains of FT. Results: Twenty-six breast cancer patients were recruited, with a consent rate of 55.9% and a 1-month attrition rate of 7.7%. All participants in the intervention group completed needs assessment and cost-related health education, with resource / service referral and personalized counseling provided as needed. The intervention significantly improved cost-related health literacy, although no statistically significant between-group difference in FT was observed. Most participants reported satisfaction and perceived the program as useful. Conclusions: The financial navigation program was feasible, acceptable, and effective in improving cost-related health literacy among breast cancer patients in China. Implications for Practice: This study generated insights to guide future implementation of full-scale RCTs with larger samples and longer durations to further explore the intervention’s effectiveness.

Financial toxicity from cancer treatment significantly impacts the quality of life among patients. Understanding how financial toxicity interacts with symptom burden is crucial for developing effective interventions. This study aimed to assess the longitudinal associations between financial toxicity and symptom burden in cancer patients in China. Conducted from November 2022 to March 2024, this prospective cohort study recruited participants from four Grade-A public hospitals across China using a convenient sampling method. Eligibility criteria included age ≥18 years, cancer diagnosis with surgery, scheduled anti-tumor treatments, and Mandarin proficiency. Financial toxicity was measured using the Comprehensive Score for Financial Toxicity (range, 0-44; higher scores indicate better financial well-being), while symptom burden was assessed with the BCPT Eight Symptom Scale (range, 0-120; higher scores reflect greater symptom annoyance) and the Memorial Symptom Assessment Scale – Short Form Psychological Subscales (range, 4-16; higher scores indicate greater burden). Assessments occurred at baseline (T1), 3 months (T2), 6 months (T3), and 12 months (T4) post-surgery. Among 378 participants (median age, 48.9 years), moderate negative associations were found between physical symptom burden and financial toxicity (r = -0.498 to -0.411) and between psychological symptom burden and financial toxicity (r = -0.493 to -0.392). A Random Intercept Cross-lagged Panel Model demonstrated that financial toxicity negatively predicted subsequent physical symptom burden (r = -0.122 to -0.166, p

Abstract The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was found to elicit synthetic lethality in methylthioadenosine phosphorylase (MTAP)‐deleted cancers, which occur in about 15% of all cancers. Here, we described a novel MAT2A inhibitor, SCR‐7952 with potent and selective antitumor effects on MTAP‐deleted cancers in both in vitro and in vivo. The cryo‐EM data indicated the high binding affinity and the allosteric binding site of SCR‐7952 on MAT2A. Different from AG‐270, SCR‐7952 exhibited little influence on metabolic enzymes and did not increase the plasma levels of bilirubin. A systematic evaluation of combination between SCR‐7952 and different types of protein arginine methyltransferase 5 (PRMT5) inhibitors indicated remarkable synergistic interactions between SCR‐7952 and the S‐adenosylmethionine‐competitive or the methylthioadenosine‐cooperative PRMT5 inhibitors, but not substrate‐competitive ones. The mechanism was via the aggravated inhibition of PRMT5 and FANCA splicing perturbations. These results indicated that SCR‐7952 could be a potential therapeutic candidate for the treatment of MTAP‐deleted cancers, both monotherapy and in combination with PRMT5 inhibitors.

Abstract Backgrounds Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. Methods The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. Results A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 − 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. Conclusion The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.

Abstract Background FLI1 is an oncogenic transcription factor that promotes diverse malignancies through mechanisms that are not fully understood. Herein, FLI1 is shown to regulate the expression of Ubiquitin Associated and SH3 Domain Containing A/B (UBASH3A/B) genes. UBASH3B and UBASH3A are found to act as an oncogene and tumor suppressor, respectively, and their combined effect determines erythroleukemia progression downstream of FLI1. Methods Promoter analysis combined with luciferase assays and chromatin immunoprecipitation (ChIP) analysis were applied on the UBASH3A/B promoters. RNAseq analysis combined with bioinformatic was used to determine the effect of knocking-down UBASH3A and UBASH3B in leukemic cells. Downstream targets of UBASH3A/B were inhibited in leukemic cells either via lentivirus-shRNAs or small molecule inhibitors. Western blotting and RT-qPCR were used to determine transcription levels, MTT assays to assess proliferation rate, and flow cytometry to examine apoptotic index. Results Knockdown of FLI1 in erythroleukemic cells identified the UBASH3A/B genes as potential downstream targets. Herein, we show that FLI1 directly binds to the UBASH3B promoter, leading to its activation and leukemic cell proliferation. In contrast, FLI1 indirectly inhibits UBASH3A transcription via GATA2, thereby antagonizing leukemic growth. These results suggest oncogenic and tumor suppressor roles for UBASH3B and UBASH3A in erythroleukemia, respectively. Mechanistically, we show that UBASH3B indirectly inhibits AP1 (FOS and JUN) expression, and that its loss leads to inhibition of apoptosis and acceleration of proliferation. UBASH3B also positively regulates the SYK gene expression and its inhibition suppresses leukemia progression. High expression of UBASH3B in diverse tumors was associated with worse prognosis. In contrast, UBASH3A knockdown in erythroleukemic cells increased proliferation; and this was associated with a dramatic induction of the HSP70 gene, HSPA1B. Accordingly, knockdown of HSPA1B in erythroleukemia cells significantly accelerated leukemic cell proliferation. Accordingly, overexpression of UBASH3A in different cancers was predominantly associated with good prognosis. These results suggest for the first time that UBASH3A plays a tumor suppressor role in part through activation of HSPA1B. Conclusions FLI1 promotes erythroleukemia progression in part by modulating expression of the oncogenic UBASH3B and tumor suppressor UBASH3A.

Objective: Yiqi Fumai Lyophilized Injection (YQFM), a Chinese medicine injection, has been widely used for the treatment of cardiovascular diseases, especially heart failure (HF). However, bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood. Materials and Methods: Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM. A compound-target network was constructed to screen bioactive compounds based on contribution index calculation. Then, an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays. Results: Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets. Particularly, ginsenosides Rb1, Rg1, Re, Rf, Rb2, Rh1, schisandrin, and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF. YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A, interleukin-2 (IL-2), IL-6, and IL-1β, as well as to regulate signaling pathways such as hypoxia-inducible factor 1, tumor necrosis factor, VEGF, and PI3K-Akt. The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats. Ginsenoside Rb1, as the major contributor from network pharmacology analysis, also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma. Conclusions: Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF. Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

Abstract Background Lovastatin, an HMG-CoA inhibitor and an effective cholesterol lowering drug, exhibits anti-neoplastic activity towards several types of cancer, although the underlying mechanism is still not fully understood. Herein, we investigated mechanism of growth inhibition of leukemic cells by lovastatin. Methods RNAseq analysis was used to explore the effect of lovastatin on gene expression in leukemic cells. An animal model of leukemia was used to test the effect of this statin in vivo. FAM83A and DDIT4 expression was knocked-downed in leukemia cells via lentivirus-shRNA. Western blotting, RT-qPCR, cell cycle analysis and apoptosis assays were used to determine the effect of lovastatin-induced growth suppression in leukemic cells in vitro. Results Lovastatin treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by Friend virus. In tissue culture, lovastatin inhibited cell proliferation through induction of G1 phase cell cycle arrest and apoptosis. Interestingly, lovastatin induced most known genes associated with cholesterol biosynthesis in leukemic cells. Moreover, it suppressed ERK1/2 phosphorylation by downregulating FAM83A and DDIT4, two mediators of MAP-Kinase signaling. RNAseq analysis of lovastatin treated leukemic cells revealed a strong induction of the tumor suppressor gene KLF2. Accordingly, lentivirus-mediated knockdown of KLF2 antagonized leukemia cell suppression induced by lovastatin, associated with higher ERK1/2 phosphorylation compared to control. We further show that KLF2 induction by lovastatin is responsible for lower expression of the FAM83A and DDIT4 oncogenes, involved in the activation of ERK1/2. KLF2 activation by lovastatin also activated a subset of cholesterol biosynthesis genes that may further contribute to leukemia suppression. Conclusions These results implicate KLF2-mediated FAM83A/DDIT4/MAPK suppression and activation of cholesterol biosynthesis as the mechanism of leukemia cell growth inhibition by lovastatin.

Abstract Background Symptom networks can provide empirical evidence for the development of personalized and precise symptom management strategies. However, few studies have explored the symptom networks of multidimensional symptom experiences in cancer survivors. The objectives of this study were to generate symptom networks of multidimensional symptom experiences in cancer survivors and explore the centrality indices and density in these symptom networks Methods Data from 1065 cancer survivors were obtained from the Shanghai CANcer Survivor (SCANS) Report. The MD Anderson Symptom Inventory was used to assess the prevalence and severity of 13 cancer‐related symptoms. We constructed contemporaneous networks with all 13 symptoms after controlling for covariates. Results Distress (rs = 9.18, rc = 0.06), sadness (rs = 9.05, rc = 0.06), and lack of appetite (rs = 9.04, rc = 0.06) had the largest values for strength and closeness. The density of the “less than 5 years” network was significantly different from that of the “5–10 years” and “over 10 years” networks (p

Synthetic mRNAs are rising rapidly as alternative therapeutic agents for delivery of proteins. However, the practical use of synthetic mRNAs has been restricted by their low cellular stability as well as poor protein production efficiency. The key roles of poly(A) tail on mRNA biology inspire us to explore the optimization of tail sequence to overcome the aforementioned limitations. Here, the systematic substitution of non-A nucleotides in the tails revealed that cytidine-containing tails can substantially enhance the protein production rate and duration of synthetic mRNAs both in vitro and in vivo. Such C-containing tails shield synthetic mRNAs from deadenylase CCR4-NOT transcription complex, as the catalytic CNOT proteins, especially CNOT6L and CNOT7, have lower efficiency in trimming of cytidine. Consistently, these enhancement effects of C-containing tails were observed on all synthetic mRNAs tested and were independent of transfection reagents and cell types. As the C-containing tails can be used along with other mRNA enhancement technologies to synergically boost protein production, we believe that these tails can be broadly used on synthetic mRNAs to directly promote their clinical applications.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 μmol/L. Hydrogen–deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Summary: Neutrophils are the first immune responders to bacterial or viral infection and play key roles in the host immune response; however, handling and investigating fresh neutrophils can be challenging. Here, we present a protocol for isolating neutrophils from the peripheral blood of healthy donors using density gradient separation method. We describe steps for morphology analysis by cytospin and immunophenotyping by flow cytometry analysis. This protocol can be used for the isolation of neutrophils from healthy and diseased individuals.For complete details on the use and execution of this protocol, please refer to Parthasarathy et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Cyclic peptides are poised to target historically difficult to drug intracellular protein–protein interactions, however, their general cell impermeability poses a challenge for characterizing function. Recent advances in microfluidics have enabled permeabilization of the cytoplasmic membrane by physical cell deformation (i.e., mechanoporation), resulting in intracellular delivery of impermeable macromolecules in vector‐ and electrophoretic‐free approaches. However, the number of payloads (e.g., peptides) and/or concentrations delivered via microfluidic mechanoporation is limited by having to pre‐mix cells and payloads, a manually intensive process. In this work, we show that cells are momentarily permeable (t1/2 = 1.1–2.8 min) after microfluidic vortex shedding (μVS) and that lower molecular weight macromolecules can be cytosolically delivered upon immediate exposure after cells are processed/permeabilized. To increase the ability to screen peptides, we built a system, dispensing‐microfluidic vortex shedding (DμVS), that integrates a μVS chip with inline microplate‐based dispensing. To do so, we synced an electronic pressure regulator, flow sensor, on/off dispense valve, and an x‐y motion platform in a software‐driven feedback loop. Using this system, we were able to deliver low microliter‐scale volumes of transiently mechanoporated cells to hundreds of wells on microtiter plates in just several minutes (e.g., 96‐well plate filled in

Aim: To determine natural compounds with inhibitory effects toward SARS-CoV-2 Mpro from Chinese herbal medicines. Materials & methods: ∼1200 natural compounds from 19 Chinese herbal medicines were collected. Computational methods including molecular docking, drug-likeness assessment, molecular dynamics simulation and molecular mechanics Poisson-Boltzmann surface area analysis were combined to obtain potent inhibitors against SARS-CoV-2 Mpro. Results: Top 20 compounds mainly originated from Ranunculus ternatus and Picrasma quassioides exhibited low binding free energies which below -9.0 kcal/mol. Compounds Japonicone G and Picrasidine T were obtained with favorable drug-likeness. Moreover, the complex of Japonicone G and Mpro had prominent stability. Conclusion: Natural compound Japonicone G is highly promising as a potent inhibitor against SARS-CoV-2 for further study.

The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51–94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4′-(trifluoromethyl)-[1,1′-biphenyl]-3,4,5-triol (6i) and 5-(9H-carbazol-2-yl) benzene-1,2,3-triol (6m) showed the most potent inhibitory activities against methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus faecalis with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 μg/mL, respectively. Compounds 3′,5′-dimethyl-[1,1′-biphenyl]-3,4,4′,5-tetraol (6e), 4′-fluoro-[1,1′-biphenyl]-3,4,5-triol (6g), and 4′-(trifluoromethyl)-[1,1′-biphenyl]-3,4,5-triol (6i) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant Acinetobacter baumannii. Study of the structure–activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, N-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.

Coronavirus main protease (3CLpro), a special cysteine protease in coronavirus family, is highly desirable in the life cycle of coronavirus. Here, molecular docking, ADMET pharmacokinetic profiles and molecular dynamics (MD) simulation were performed to develop specific 3CLpro inhibitor. The results showed that the 137 compounds originated from Chinese herbal have good binding affinity to 3CLpro. Among these, Cleomiscosin C, (+)-Norchelidonine, Protopine, Turkiyenine, Isochelidonine and Mallotucin A possessed prominent drug-likeness properties. Cleomiscosin C and Turkiyenine exhibited excellent pharmacokinetic profiles. Furthermore, the complex of Cleomiscosin C with SARS-CoV-2 main protease presented high stability. The findings in this work indicated that Cleomiscosin C is highly promising as a potential 3CLpro inhibitor, thus facilitating the development of effective drugs for COVID-19.

Introduction: The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. Objectives: This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. Methods: We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. Results: The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. Conclusion: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

Summary: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.

ObjectiveTo test the reliability and validity of the Chinese version of the Walsh Family Resilience Questionnaire among community-dwelling disabled elderly individuals (WFRQ-CE).MethodsConvenience sampling was used to select 566 dyads of disabled elderly individuals and their caregivers. The Walsh Family Resilience Questionnaire Chinese Version (WFRQ-C) was tested among elderly individuals. The Family Care Capacity Scale for Elderly Patients (FCCSE) was used as a concurrent validation tool for the caregivers, and the Psychological Resilience Scale (CD-RISC-10), and the Social Support Assessment (SSRS-10) were used as concurrent validation tools for both the elderly individuals and the caregivers.ResultsExploratory factor analysis (EFA) revealed four common factors–“Family belief,” “Organization and problem solving,” “Family communication,” and “Utilization of external resources”–with a cumulative variance contribution rate of 56.94%. Confirmatory factor analysis (CFA) yielded the following fit indices: chi-square/freedom degree (χ2/df) = 2.007, Tucker Lewis index (TLI) = 0.900, incremental fit index (IFI) = 0.917, comparative fit index (CFI) = 0.916, parsimony goodness-of-fit index (PGFI) = 0.681, and root-mean-square error of approximation (RMSEA) = 0.060. The concurrent scales were significantly correlated with the WFRQ-C total score and the scores for each factor (r values between 0.23 and 0.60, P < 0.01). The Cronbach’s alpha coefficient was 0.93 for the WFRQ-CE and 0.87, 0.83, 0.89, and 0.65 for the four factors; the retest reliability was 0.96 for the total scale and 0.95, 0.92, 0.92, and 0.95 for the four factors; the split-half reliability was 0.85 for the total scale, and 0.81, 0.78, 0.79, and 0.68 for the four factors.ConclusionThe WFRQ-CE has good reliability and validity among community-dwelling disabled elderly individuals and can be used to evaluate the level of family resilience.

With the widespread application and functional complexity of deep neural networks (DNNs), the demand for training samples is increasing. This elevated requirement also extends to DNN-based SAR object detection. Most public SAR object detection datasets are oriented to marine targets such as ships, while data sets oriented to land targets are relatively rare, though they are an effective way to improve the land object detection capability of deep models through SAR sample generation. In this paper, a synthesis generation collaborative SAR sample augmentation framework is proposed to achieve flexible and diverse high-quality sample augmentation. First, a semantic-layout-guided image synthesis strategy is proposed to generate diverse detection samples. The issues of object location rationality and object layout diversity are also addressed. Meanwhile, a pix2pixGAN network guided by layout maps is utilized to achieve diverse background augmentation. Second, a progressive training strategy of diffusion models is proposed to achieve semantically controllable SAR sample generation to further improve the diversity of scene clutter. Finally, a sample cleaning method considering distribution migration and network filtering is employed to further improve the quality of detection samples. The experimental results show that this semantic synthesis generation method can outperform existing sample augmentation methods, leading to a comprehensive improvement in the accuracy metrics of classical detection networks.

Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation. The complicated composition rendered its chemical analysis and effective-component elucidation. In this study, we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK. First, UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations. Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity. Then, anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay. Finally, major analytes forsythosides H, I, A (8–10), and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK. The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

By reviewing scientific literature, researchers may obtain a comprehensive understanding of field developments, keeping abreast of the current research status and hotspot shifts. The evolution pattern of keywords is supposed to be an efficient indicator in revealing the shifting and sustainability configuration of scientific concepts, ideas, and research hotspots. Here we take an extensive investigation of the evolution of keywords among all publications in PNAS Social Sciences from 1990 to 2021. Statistical tests show the keyword mention time series always accompanied by the emergence of a log-normal distribution. Additionally, we introduce a novel schema of four patterns (TELS), which are Transient impact type, Explosive impact type, Large impact type, and Small impact type, respectively, to illustrate the evolution of keywords. The TELS schema can be used to capture the whole life circle feature of any proposed keyword, from a pool of candidates. By dividing the entire time into four periods, we also introduce the concept of elite keywords to reveal the temporal feature of social sciences focus. An explicit transition from anthropology research to neuroscience and social problems research can be observed from the evolution diagram. We argue that the proposed method is of general sense and might be applicable to other fields of science.

Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that heterozygous Drosophila with the AOS-like Su(H) allele behave in an opposing manner to heterozygous flies with a Su(H) null allele, due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants have decreased DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby the AOS-associated RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.

Shape memory polymers (SMPs) have a wide range of potential applications in many fields. In particular, electrically driven SMPs have attracted increasing attention due to their unique electrical deformation behaviors. Carbon nanotubes (CNTs) are often used as SMP conductive fillers because of their excellent electrical conductivities. However, raw CNTs do not disperse into the polymer matrix well. This strictly limits their use. In this study, to improve their dispersion performance characteristics in the polymer matrix, hydroxylated multi-walled carbon nanotubes (MWCNT-OHs) were functionalized with octadecyl isocyanate (i-MWCNTs). Polyurethane with shape memory properties (SMPU) was synthesized using polycaprolactone diol (PCL-diol), hexamethylene diisocyanate (HDI), and 1,4-butanediol (BDO) at a 1:5:4 ratio. Then, electroactive shape memory composites were developed by blending SMPU with i-MWCNTs to produce SMPU/i-MWCNTs. The functionalized i-MWCNTs exhibited better dispersibility characteristics in organic solvents and SMPU composites than the MWCNT-OHs. The addition of i-MWCNTs reduced the crystallinity of SMPU without affecting the original chemical structure. In addition, the hydrogen bond index and melting temperature of the SMPU soft segment decreased significantly, and the thermal decomposition temperatures of the composites increased. The SMPU/i-MWCNT composites exhibited conductivity when the i-MWCNT content was 0.5 wt%. This conductivity increased with the i-MWCNT content. In addition, when the i-MWCNT content exceeded 1 wt%, the composite temperature could increase beyond 60°C within 140 s and the temporary structure could be restored to its initial state within 120 s using a voltage of 30 eV. Therefore, the functionalized CNTs exhibit excellent potential for use in the development of electroactive shape memory composites, which may be used in flexible electronics and other fields.

Auxins as an important class of phytohormones play essential roles in plant life cycle; therefore, developing compounds with auxin-like properties for plant growth regulation and weed control applications is of great significance. Herein, we reported the design, synthesis, and herbicidal activity evaluation of a series of novel indole-3-carboxylic acid derivatives as auxin receptor protein TIR1 antagonists. Petri dish herbicidal activity assay demonstrated that most of the as-synthesized target compounds exhibited good-to-excellent inhibition effects (60–97% inhibitory rates) on roots and shoots of both dicotyledonous rape (B. napus) and monocotyledonous barnyard grass (E. crus-galli). The inhibition rates of compounds 10d and 10h reached up to 96% and 95% for the root of rape (B. napus) at 100 mg/L, and they also maintained 92% and 93% inhibition rates even if at 10 mg/L, respectively. Molecular docking revealed that the interactions between these synthesized target compounds and TIR1 protein include tight π–π stacking, hydrogen bond, and hydrophobic interactions. This work expands the range of auxin chemistry for the development of new auxin mimic herbicides.

Essential oils from aerial parts of the herbs Peganum harmala and Nepeta cataria, and leaves of the tree Phellodendron amurense were analyzed by GC-FID and GC-MS, and their larvicidal activities were assayed on the early fourth instar larvae of Aedes aegypti. The major constituents of the oils were limonene (14.5%) and thymol (11.5%) in P. harmala, thymol (46.5%), 4aα,7α,7aβ-nepetalactone (18.3%) and 4aα,7β,7aα-neptalactone (19.7%) in N. cataria, eugenol (14.5%) andγ-eudesmol (9.5%) in P. amurense.The oil of N. cataria had a strong larvicidal activity (LC50

4-hydroxyl coumarin (HC), an important intermediate during the synthesis procedure of rodenticide and anti-cardiovascular drug, shows highly medicinal value and economic value. To achieve the efficient adsorption of HC from natural biological samples, a novel magnetic surface molecularly imprinted polymer (HC/SMIPs) was constructed by employing methacrylic acid (MAA) as functional monomer, organic silane modified magnetic particles as matrix carrier and HC as template molecule. Due to the numerous specific imprinted cavities on the HC/SMIPs, the maximum adsorption capacity of HC/SMIPs for 4-hydroxycoumarin could reach to 22.78 mg g−1 within 20 min. In addition, HC/SMIPs exhibited highly selective adsorption for 4-hydroxycoumarin compared with other active drug molecules (osthole and rutin) and showed excellent regeneration performance. After 8 cycles of adsorption-desorption tests, the adsorption capacity of HC/SMIPs just slightly decreased by 6.64%. The efficient selective removal and easy recycle of 4-hydroxycoumarin from biological samples by HC/SMIPs made a highly promising to advance the application of imprinting polymers in complex practical environments.

The efficient biosynthesis of chiral amines at an industrial scale to meet the high demand from industries that require chiral amines as precursors is challenging due to the poor stability and low catalytic efficiency of ω-transaminases (ω-TAs). Herein, this study adopted a green and efficient solvent engineering method to explore the effects of various aqueous solutions of deep eutectic solvents (DESs) as cosolvents on the catalytic efficiency and stability of ω-TA. Binary- and ternary-based DESs were used as cosolvents in enhancing the catalytic activity and stability of a ω-TA variant from Aspergillus terreus (E133A). The enzyme exhibited a higher catalytic activity in a ternary-based DES that was 2.4-fold higher than in conventional buffer. Moreover, the thermal stability was enhanced by a magnitude of 2.7, with an improvement in storage stability. Molecular docking studies illustrated that the most potent DES established strong hydrogen bond interactions with the enzyme’s amino acid, which enhanced the catalytic efficiency and improved the stability of the ω-TA. Molecular docking is essential in designing DESs for a specific enzyme.

Traditional engineering design approaches primarily solve technical problems and often ignore the importance of human factors. To reduce human errors and workload in power electronics, this paper proposes a switched-mode power supply design (SMPS) assistant system based on Fuzzy Cognitive Maps (FCMs). This system incorporates both technical requirements and human factors that involve designers' knowledge and skills in the SMPS design domain. First, we identify the critical concepts from power management lab kits and power electronics books, and extract latent sub-skills of SMPS design using exploratory factor analysis to build the starting concept list of FCM. Second, we use factor analysis and correlation analysis to determine the causal weights between the captured components to build the initial FCM based on the starting concept list of FCM. Third, through interviews with subject-matter experts, we get their inputs on the initial main map and capture their individual FCMs. Then, we integrate experts' individual FCMs with different weights. After that, we determine the degree of fuzzification of the threshold function through analyzing data collected based on the prediction results of the only decision concept in the proposed FCM - SMPS quality. Two WHAT-IF scenarios are analyzed based on different inputs using the FCM Expert tool. The scenario test results provide guidelines to designers in terms of knowledge or skills improvements and power supply debugging. Finally, we evaluate the proposed system using eight scenarios. The evaluation results of components' actual states are consistent with their preferred states, which suggests that the proposed FCM-based assistant system is reliable and effective. The proposed system provides useful guidelines in terms of knowledge or skills improvements for SMPS designers and can help improve the power supply design process.

Alcoholic liver disease (ALD) is a complicated disease which can lead to hepatocellular carcinoma; however, there is a lack of satisfactory therapeutics. Dehydroeburicoic acid (DEA) (1), a triterpenoid isolated from Antrodia cinnamomea, has been reported to act against ALD, but its mechanisms of action are still not clear. In this study, we report for the first time the use of DEA (1) as a dual inhibitor of the Keap1–Nrf2 protein–protein interaction (PPI) and GSK3β in an in vitro ALD cell model. DEA (1) engages Keap1 to disrupt the Keap1–Nrf2 PPI and inhibits GSK3β to restore Nrf2 activity in a Keap1-independent fashion. DEA (1) promotes Nrf2 nuclear translocation to activate downstream antioxidant genes. Importantly, DEA (1) restores the mitochondrial dysfunction induced by ethanol and generates antioxidant activity in the ALD cell model with minimal toxicity. We anticipate that DEA (1) could be a potential scaffold for the further development of clinical agents for treating ALD.

Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monomeric CSL sites and cooperative dimer sites called Su(H) paired sites (SPS). Intriguingly, the CSL TF can also bind co-repressors to negatively regulate transcription via these same sites. Here, we tested how synthetic enhancers with monomeric CSL sites versus dimeric SPSs bind Drosophila Su(H) complexes in vitro and mediate transcriptional outcomes in vivo. Our findings reveal that while the Su(H)/Hairless co-repressor complex similarly binds SPS and CSL sites in an additive manner, the Notch activation complex binds SPSs, but not CSL sites, in a cooperative manner. Moreover, transgenic reporters with SPSs mediate stronger, more consistent transcription and are more resistant to increased Hairless co-repressor expression compared to reporters with the same number of CSL sites. These findings support a model in which SPS containing enhancers preferentially recruit cooperative Notch activation complexes over Hairless repression complexes to ensure consistent target gene activation.

Orobanche and Striga are parasitic weeds extremely well adapted to the life cycle of their host plants. They cannot be eliminated by conventional weed control methods. Suicidal germination induced by strigolactones (SLs) analogs is an option to control these weeds. Here, we reported two new halogenated (+)-GR24 analogs, named 7-bromo-GR24 (7BrGR24) and 7-fluoro-GR24 (7FGR24), which were synthesized using commercially available materials following simple steps. Both compounds strongly promoted seed germination of Orobanche cumana. Their EC50 values of 2.3±0.28×10−8M (7BrGR24) and 0.97±0.29×10−8M (7FGR24) were 3- and 5-fold lower, respectively, than those of (+)-GR24 and rac-GR24 (EC50=5.1±1.32–5.3±1.44×10−8; p

Cooperative DNA binding is a key feature of transcriptional regulation. Here we examined the role of cooperativity in Notch signaling by CRISPR-mediated engineering of mice in which neither Notch1 nor Notch2 can homo- or heterodimerize, essential for cooperative binding to sequence-paired sites (SPS) located near many Notch-regulated genes. Although most known Notch-dependent phenotypes were unaffected in Notch1/2 dimer-deficient mice, a subset of tissues proved highly sensitive to loss of cooperativity. These phenotypes include heart development, compromised viability in combination with low gene dose, and the gut, developing ulcerative colitis in response to 1% dextran sulfate sodium (DSS). The most striking phenotypes-gender imbalance and splenic marginal zone B-cell lymphoma-emerged in combination with gene dose reduction or when challenged by chronic fur mite infestation. This study highlights the role of the environment in malignancy and colitis and is consistent with Notch-dependent anti-parasite immune responses being compromised in Notch dimer-deficient animals.

Triple-negative breast cancer (TNBC) comprises lethal malignancies with limited treatment options. Chimeric antigen receptor T (CAR-T) cell therapy is an effective immunotherapeutic strategy that has demonstrated unprecedented efficacy in the treatment of hematological malignancies but has shown limited success in the management of some solid tumors. Many malignant tumors are related to increased expression of intercellular adhesion molecule-1 (ICAM1), providing a rationale for ICAM1-specific immunotherapies for the treatment of cancer. Here, we validated the expression of ICAM1 in TNBC tissues. Subsequently, we generated a phage-displayed single-chain variable fragment (scFv) library using splenocytes from ICAM1-immunized mice and selected a novel ICAM1-specific scFv, mG2-scFv. Using mG2-scFv as the extracellular antigen binding domain, we constructed ICAM1-specific CAR-T cells and demonstrated the robust and specific killing of TNBC cell lines in vitro. Most importantly, in the TNBC mouse model, ICAM1-specific CAR-T cells significantly reduced the growth of the TNBC tumor, resulting in long-term remission and improved survival. Together, these results indicated that ICAM1-specific CAR-T cells have high therapeutic potential against ICAM1-positive TNBC tumors.

Dirhodium(II) complex-catalyzed [3 + 2] reactions between N-arylaminocyclopropanes and alkyne derivatives are described. The cycloaddition products proved to be versatile synthetic intermediates. trans-Cyclic β-amino acids and derivatives thereof can be conveniently synthesized using this cycloaddition protocol.

Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage. Here, we unexpectedly found that inserting an enhancer containing pioneer transcription factor sites coupled to Notch dimer sites can induce a subset of Notch haploinsufficiency phenotypes in Drosophila with wild type Notch gene dose. Using Drosophila genetics, we show that this enhancer induces Notch phenotypes in a Cdk8-dependent, transcription-independent manner. We further combined mathematical modeling with quantitative trait and expression analysis to build a model that describes how changes in Notch signal production versus degradation differentially impact cellular outcomes that require long versus short signal duration. Altogether, these findings support a ‘bind and discard’ mechanism in which enhancers with specific binding sites promote rapid Cdk8-dependent Notch turnover, and thereby reduce Notch-dependent transcription at other loci and sensitize tissues to gene dose based upon signal duration.

The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.

Abstract During last decades, sensor elements based on the fiber Bragg grating (FBG) have been widely studied and developed due to the advantages of immunity to electromagnetic interference, compact size, high precision, and so on. The FBG itself is sensitive to axial strain and temperature variation directly and can indirectly measure these complex physical parameters, such as pressure, displacement, and vibration, by using some specially designed elastic structures to convert them into the axial strain of the FBG. Whether the FBG is fixed on the measured object to measure the strain directly or fixed on an elastic structure body to measure other physical quantities, these types of FBGs could be collectively called as strain sensing FBGs. The packaging of the FBG has important influence on FBG characteristics that directly affect the measurement accuracy, such as strain transfer, temperature characteristic, and spectral shape. This paper summarizes the packaging methods and corresponding temperature compensation methods of the currently reported strain sensing FBGs, focusing especially on fully pasted FBG, pre-stretched FBG with double-end fixed, and metallic packaging. Furthermore, the advantages and drawbacks of different packaging methods have been analyzed, which can provide a reference for future researches.

Context: Scutellaria baicalensis Georgi (Lamiaceae) is a popular medicinal plant. Its roots are used as the famous traditional Chinese medicine Huang-Qin, which is recorded in Chinese Pharmacopoeia, European Pharmacopoeia, and British Pharmacopoeia. Objective: This review comprehensively summarizes research progress in phytochemistry, pharmacology, and flavonoid biosynthesis of S. baicalensis. Methods: English and Chinese literature from 1973 to March 2018 was collected from databases including Web of Science, SciFinder, PubMed, Elsevier, Baidu Scholar (Chinese), and CNKI (Chinese). Scutellaria baicalensis, chemical constituents, phytochemistry, biological activities, and biosynthesis were used as the key words. Results: A total of 126 small molecules (1–126) and 6 polysaccharides have been isolated from S. baicalensis. The small molecules can be classified into four structural types, namely, free flavonoids, flavonoid glycosides, phenylethanoid glycosides, and other small molecules. Extracts of S. baicalensis and its major chemical constituents have been reported to possess anti-viral, anti-tumor, anti-bacterial, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective activities. Key steps in the biosynthetic pathways of Scutellaria flavonoids have also been summarized. Conclusions: This article could be helpful for researchers who are interested in the chemical constituents, bioactivities, biosynthesis, and clinical applications of S. baicalensis.

AIM: To observe the structure changes of vitreous and retina after YAG laser ablation in patients with physiological vitreous floaters.METHODS: The selected 40 patients of physiological vitreous floaters, before YAG laser ablation, were checked for best corrected visual acuity, non-contact intraocular pressure, took their anterior segment photos, measured their foveola thickness(FT)and retinal nerve fiber layer(RNFL)by OCT. The YAG laser ablation was completed by one experienced surgeon. After the YAG laser ablation, all patients were checked for non-contact intraocular pressure and gave pranoprofen eye drops tid for 3d. At 2d, 1wk, 1 and 3mo after the surgery, they were reviewed for best corrected visual acuity, non-contact intraocular pressure. At 3mo later anterior segment photos were taken. At 1wk, 1 and 3mo after the surgery, FT and RNFL were measured again.RESULTS: The postoperative 2d, 1wk, 1 and 3mo, best corrected visual acuity, non-contact intraocular pressure of the patients had no significant difference with preoperative(P>0.05). The preoperative anterior segment photos showed obvious single or sheet opacity of vitreous, the postoperative 3mo photos showed that vitreous opacities decreased or disappeared, no other abnormal changes were found. The preoperative OCT data showed that FT was 214.60±9.35μm, the postoperative 1wk, 1 and 3mo FT were 213.75±9.07μm, 213.40±8.83μm, 213.85±9.22μm. The preoperative RNFL were upper 130.26±14.23μm, lower 133.15±14.46μm, nasal 82.48±13.50μm, temporal 75.40±11.89μm; The postoperative 1wk RNFL were upper 130.02±14.02μm, lower 132.99±14.05μm, nasal 82.35±13.07μm, temporal 75.42±11.66μm. The postoperative 1mo RNFL were upper 130.28±14.43μm, lower 133.08±13.99μm, nasal 82.31±13.72μm, temporal 75.45±12.03μm. The postoperative 3mo RNFL were upper 130.43±14.30μm, lower 133.22±14.20μm, nasal 82.27±13.11μm, temporal 75.46±11.91μm. The differences of preoperative and postoperative 1wk, 1 and 3mo FT and RNFL had no statistical significance(P>0.05). CONCLUSION: YAG laser ablation has no adverse effects to vitreous and retinal structure in patients with physiological vitreous floaters, it is effective and safe.

Angucyclinones are aromatic polyketides that possess impressive structural diversity and significant biological activities. The structural diversity of these natural products is attributed to various enzymatic or nonenzymatic modifications on their tetracyclic benz(a)anthracene skeleton. Previously, we discovered an unusual phenylamine-incorporated angucyclinone (1) from a marine Streptomyces sp. PKU-MA00218, and identified that it was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone (2) with phenylamine. In this study, we tested the nonenzymatic conversion of 2 with more phenylamine analogues, to expand the utility of this feasible conversion in unusual angucyclinones generation. The (3-ethynyl)phenylamine and disubstituted analogues including (3,4-dimethyl)phenylamine, (3,4-methylenedioxy)phenylamine, and (4-bromo-3-methyl)phenylamine were used in the conversion of 2, which was isolated from the fermentation of Streptomyces sp. PKU-MA00218. All four phenylamine analogues were incorporated into 2 efficiently under mild conditions, generating new compounds 3–6. The activation of 3–6 on nuclear factor erythroid 2-related factor 2 (Nrf2) transcription were tested, which showed that 4 possessing a dimethyl-substitution gave most potent activity. These results evidenced that disubstitutions on phenylamine can be roughly tolerated in the nonenzymatic reactions with 2, suggesting extended applications of more disubstituted phenylamines incorporation to generate new bioactive angucyclinones in the future.

Interspecific hybridization is an effective strategy in Kalanchoe breeding programs for the introduction of new traits. Wild species within the Kalanchoe genus are valuable genetic resources for providing new horticulture traits and to improve environmental adaptations. However, reproductive barriers associated with fertilization and hybrid sterility must be overcome to produce fertile hybrid progenies. To approach the breeding objectives for Kalanchoe cut flower cultivars with long stem traits and adaptation to tropical/subtropical regions, a tropical species endemic to Taiwan, Kalanchoe garambiensis Kudo, was used as a parent to cross with other long stem Kalanchoe species. Reciprocal crossing was effective in overcoming interspecific unilateral incompatibility in our crossed pairs. One superior hybrid, ‘103-1’, produced capsules without seeds by selfing and backcrossing with pollens from either parent. Other than the seedless trait, failure of pollen releasing from anther, pollen aggregation and no pollen germination in ‘103-1’ suggested its F1 sterility. Colchicine treatments on apical buds of ‘103-1’ successfully overcame potential meiotic abnormalities by doubling ploidy. For the first time, fertile interspecific hybrids of K. garambiensis and K. nyikae Engler were generated. The fertile hybrid has further produced progeny populations by crossing with K. nyikae or K. blossfeldiana von Poelln, ‘Ida’.

Balancing energy generation and consumption is essential for smoothing the power grids. The mismatch between energy supply and demand would not only increase the cost on both sides, but also has a great impact on the stability of the system. This paper proposes a novel energy sharing mechanism (ESM) to facilitate the consumption of local energy. With the help of the ESM, multiple prosumers have an opportunity to share surplus energy with neighboring prosumers. The problem is formulated as a leader–follower framework based on the Stackelberg game theory. To address the aforementioned problems, a deep deterministic policy gradient (DDPG) is applied to solve the Nash equilibrium (NE). The numerical results demonstrate that the proposed method is more stable than the conventional reinforcement learning (RL) algorithm. Moreover, the proposed method can converge to NE and find a relatively good energy sharing (ES) pricing strategy without knowing the specific system information. In short, it is notable that the proposed ESM can be seen as a win–win strategy for both prosumers and the power system.

Objective To examine the efficacy and safety of yttrium-aluminium garnet (YAG) laser vitreolysis for the treatment of vitreous floaters. Methods Consecutive adult patients with symptomatic vitreous floaters who attended Chongqing General Hospital from April to December 2016 were included in this prospective study. Patients had >3 mm between the vitreous opacity and retina/lens and acceptable quality peri-papillary Optical Coherence Tomography (OCT) images (i.e., signal strength ≥5). Those with history of glaucoma, severe cataracts, vitreous haemorrhages, retinal holes and/or macular disease were excluded from the study. Best corrected visual acuity (BCVA) and non-contact intraocular pressure (IOP) were measured before and for up to 6 months post-YAG laser vitreolysis. Anterior segment photography and peripapillary retinal nerve fibre layer (RNFL) measured by OCT were taken before and 6 months post-procedure. Questionnaires on patient satisfaction were completed 6 months post-procedure. Results No statistically significant differences in BCVA and IOP were observed before or after treatment. Anterior segment photography showed that vitreous opacities partially or completely disappeared after YAG laser treatment. The thickness of RNFL in four directions (upper, below, nasal and temporal) was not statistically significant different before or 6 months after the procedure. 75% patients reported significant improvement and 25% reported moderate improvement. Conclusion The results of this study conducted in a cohort of 30 Chinese patients showed that YAG laser vitreolysis was a well-tolerated and effective treatment for vitreous floaters. Randomised, controlled trials involving large numbers of participants monitored over an extended follow up period are required to confirm these results.

Herbal medicines are commonly used as compound formulas in clinical practice to achieve optimal therapeutic effects. However, the combination mechanisms usually lack solid evidence. In this study, we report synergistic interactions through altering pharmacokinetics in Gegen-Qinlian Decoction (GQD), an anti-diabetic Chinese medicine formula. A multi-component pharmacokinetic study of GQD and the single herbs was conducted by simultaneously monitoring 42 major bioactive compounds (markers) in rats plasma using LC/MS/MS within 30 min. GQD could remarkably improve the plasma concentrations of berberine (BER) and other alkaloids in Huang-Lian by at least 30%, and glycyrrhizic acid (GLY) from Gan-Cao played a major role. A Caco-2 cell monolayer test indicated that GLY improved the permeability of BER by inhibiting P-glycoprotein. Although GLY alone did not show observable effects, the co-administration of GLY (ig, 50 or 80 mg/kg) could improve the anti-diabetic effects of berberine (ig, 50 mg/kg) in db/db mice in a dose-dependent manner. The blood glucose decreased by 46.9%, whereas the insulin level increased by 40.8% compared to the control group. This is one of the most systematic studies on the pharmacokinetics of Chinese medicine formulas, and the results demonstrate the significance of pharmacokinetic study in elucidating the combination mechanisms of compound formulas.