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A checklist of 488 fall webworm Hyphantria cunea (Drury) natural enemies was compiled based on documentation in previous research across its world distribution, including 289 predators and 199 parasitoids. Predators in the checklist include 67 species from 17 families of Insecta, 1 species of Chilopoda, 183 species from 22 families of Arachnida, 1 species of Reptilia, 4 species from 2 families of Amphibia, 33 species from 18 families of Aves. In addition, the checklist includes fall webworm parasitoids from 18 families of Insecta. Among continents, 128 predators and 76 parasitoids were distributed in North America, 78 predators and 62 parasitoids in Asia, and 88 predators and 68 parasitoids in Europe.

Tumor organoids, derived from tumor tissues, are three-dimensional structures created in vitro to mimic in vivo tumor growth. They possess comparable genetic lineage and pathological characteristics to the original tumor, making them a promising research platform for studying tumor biology. In recent years, significant advancements in techniques such as microfluidics, cell co-culture and vascularization have greatly promoted the development of Organ-on-a-Chip (OoC) and expanded the applications of tumor organoid models in both basic and clinical translational research. These advancements include leveraging tumor organoid models to investigate drug resistance mechanisms, perform drug screening, and facilitate clinical trials of precisional therapy. However, current organoid models still face several limitations, including the instability of cell culture quality, low cost-effectiveness, and the inability to accurately replicate the complex tumor microenvironment and spatial structures. Further research is needed to overcome these technical bottlenecks and improve the application of organoid models in cancer research, thereby further enhancing the depth of tumor research. This review summarized the development history and latest progress of tumor organoids. In terms of the latest applications of tumor organoids, this article reviewed disease modeling, research and development of innovative tumor drugs, and their application in personalized treatment. It also summarized the recent clinical researches of organoids; In addition, this review provided a detailed introduction to the technological progress of tumor organoids, including the development of novel culture devices, simulation of tumor microenvironment, and induction of angiogenesis. In summary, this review explored the latest developments, defects and future directions in the research of tumor organoids, aiming to provide reference for the study of tumor organoids.

Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract Financial restatements significantly measure financial reporting quality, introducing uncertainty, undermining trust, and triggering adverse reactions in financial markets. This paper examines how the supply of tax information affects financial restatements. The literature lacks compelling evidence about the relationship between tax information and financial restatements. From one perspective, enhancing the transparency of corporate tax information can diminish the occurrence of financial restatements. From another perspective, increasing the accessibility of tax information could lead to increased financial restatements. We reconcile these competing associations, exploiting a natural experiment induced by the rollout of Taxation Administration Information System III (CTAIS-3) in China. Using a difference-in-difference approach, we find that firms in areas implementing CTAIS-3 experience a significant decrease in financial restatements. Our results remain robust across various indicators of financial reporting quality. Furthermore, we demonstrate that information asymmetry is a driving factor behind our results, emphasizing the government’s proactive role in enhancing the quality of corporate financial disclosure.

Abstract Background The endosperm serves as the primary source of nutrients for maize (Zea mays L.) kernel embryo development and germination. Positioned at the base of the endosperm, the transfer cells (TCs) of the basal endosperm transfer layer (BETL) generate cell wall ingrowths, which enhance the connectivity between the maternal plant and the developing kernels. These TCs play a crucial role in nutrient transport and defense against pathogens. The molecular mechanism underlying BETL development in maize remains unraveled. Results This study demonstrated that the MYB-related transcription factor ZmMYBR29, exhibited specific expression in the basal cellularized endosperm, as evidenced by in situ hybridization analysis. Utilizing the CRISPR/Cas9 system, we successfully generated a loss-of-function homozygous zmmybr29 mutant, which presented with smaller kernel size. Observation of histological sections revealed abnormal development and disrupted morphology of the cell wall ingrowths in the BETL. The average grain filling rate decreased significantly by 26.7% in zmmybr29 mutant in comparison to the wild type, which impacted the dry matter accumulation within the kernels and ultimately led to a decrease in grain weight. Analysis of RNA-seq data revealed downregulated expression of genes associated with starch synthesis and carbohydrate metabolism in the mutant. Furthermore, transcriptomic profiling identified 23 genes that expressed specifically in BETL, and the majority of these genes exhibited altered expression patterns in zmmybr29 mutant. Conclusions In summary, ZmMYBR29 encodes a MYB-related transcription factor that is expressed specifically in BETL, resulting in the downregulation of genes associated with kernel development. Furthermore, ZmMYBR29 influences kernels weight by affecting the grain filling rate, providing a new perspective for the complementation of the molecular regulatory network in maize endosperm development.

Abstract The system time of the four major navigation satellite systems is mainly maintained by multiple high-performance atomic clocks at ground stations. This operational mode relies heavily on the support of ground stations. To enhance the high-precision autonomous timing capability of next-generation navigation satellites, it is necessary to autonomously generate a comprehensive space-based time scale on orbit and make long-term, high-precision predictions for the clock error of this time scale. In order to solve these two problems, this paper proposed a two-level satellite timing system, and used multiple time-keeping node satellites to generate a more stable space-based time scale. Then this paper used the sparse sampling Long Short-Term Memory (LSTM) algorithm to improve the accuracy of clock error long-term prediction on space-based time scale. After simulation, at sampling times of 300 s, 8.64 × 104 s, and 1 × 106 s, the frequency stabilities of the spaceborne timescale reach 1.35 × 10–15, 3.37 × 10–16, and 2.81 × 10–16, respectively. When applying the improved clock error prediction algorithm, the ten-day prediction error is 3.16 × 10–10 s. Compared with those of the continuous sampling LSTM, Kalman filter, polynomial and quadratic polynomial models, the corresponding prediction accuracies are 1.72, 1.56, 1.83 and 1.36 times greater, respectively.

Inflammatory cytokine storms can trigger disease exacerbation and even death and have reached a consensus in the clinical treatment of acute organ failure. However, the existing strategies remain a great challenge to efficiently suppress inflammatory cytokine storms for promoting organ repair and regeneration. Herein, fully human umbilical cord (UC)-derived adhesive materials (UCAM) that integrate decellularized extracellular matrix (ECM) nanofiber hydrogel and homologous mesenchymal stem cells (MSCs) are demonstrated to greatly suppress inflammatory cytokine storms, demonstrating high efficacy in treating acute liver failure (ALF) in rats with 90% hepatectomy. The UC-derived adhesive materials have the capacity to secrete a significant quantity of cytokines by MSCs to recruit activated immune cells to migrate into their ECM nanofiber networks, segregating them away from the infection area and thereby greatly suppressing the inflammatory cytokine storms. As expected, the UC-derived adhesive materials can significantly promote hepatocyte proliferation to achieve functional recovery and regeneration of the liver, significantly improving the survival rate in rats. Our fully human UC-derived adhesive materials provide a new avenue in suppressing inflammatory cytokine storms for promoting organ regeneration that would be really utility in clinical organ transplantation-related treatment.

Summary: This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.

Objective·To investigate the distribution characteristics of vaginal flora in patients with cervical incompetence (CIC), and the effect of cervical cerclage on pregnancy outcome in patients with CIC with abnormal vaginal flora.Methods·A total of 1 261 pregnant women participated in the study. According to the diagnosis, they were divided into cervical incompetence group (CIC group) and normal pregnancy group (NP group). The CIC group patients randomly received cervical cerclage (CIC-C group) or expectation therapy (CIC-E group). Vaginal secretion samples of the patients in the groups were collected and analyzed in the laboratory. Meanwhile, through the results of vaginal flora, the CIC-C group and CIC-E group were further divided into normal vaginal flora groups (CIC-C-N group and CIC-E-N group) and abnormal vaginal flora groups (CIC-C-A group and CIC-E-A group). All groups were processed accordingly and analyzed on pregnancy outcomes. T-test and Chi-squared test were used for comparison between the groups, and One-way ANOVA was used for comparison among the three groups. Statistical significance was accepted at a value of P

The ability of an ecosystem to provide services differs from its actual consumption and use by human society. Overuse of ecosystems can degrade ecosystems. In order to evaluate the supply capacity and use status of the ecosystem in Miyun County, so as to better apply the ecosystem services to different policies and management, the supply and use of 10 types of ecosystem services in Miyun County were calculated by using value indicators, namely potential gross ecosystem product (GEP) and actual gross ecosystem product. The results show that: (1) In 2020, potential gross ecosystem product of Miyun County is 254.32 billion yuan, and actual gross ecosystem product is 53.28 billion yuan, accounting for 21% of the potential gross ecosystem product. (2) Among all kinds of ecosystem services, the contribution of water conservation services in potential gross ecosystem product is the highest, and the contribution of climate regulation services in actual gross ecosystem product is the highest. (3) The contribution of wetland was the highest in potential gross ecosystem product, while the contribution of forest was the highest in actual gross ecosystem product. (4) Natural ecosystem area and vegetation coverage are the main factors affecting potential gross ecosystem product, while actual gross ecosystem product is mainly affected by GDP and population. (5) By studying the potential supply and actual use of ecosystem services, we evaluated and distinguished between the services that ecosystem could produce and the services that were actually used by humans, and compared the supply capacity and actual use to assess the sustainability of ecosystem services, in order to formulate different policies and management measures for gross ecosystem product surplus and deficit regions. Potential gross ecosystem product could provide data support for the assessment of ecological protection benefits. Actual gross ecosystem product could be included in the system of national accounts, and as a standard for ecological compensation and ecological trading. Confusing potential supply and actual use in policy application would affect the effect of policy implementation, and distinguishing them could ensure policy implementation. The relative size of the relationship between the two could reflect the present and future levels of human well-being in a region. Both together provided management basis and policy-making support for guiding regional ecological protection and sustainable development.

Summary: Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 μM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

Objective By collecting the patient information in the Colon Cancer Database of Peking Union Medical College Hospital since its establishment, we aim to demonstrate the completeness of the clinicopathological characteristics and follow-up data to provide reference for single-center database establishment. Methods We collected 33 surgical patient information entries from the single-center prospective registry database of Colon Cancer at Peking Union Medical College Hospital from January 5, 2016 to May 11, 2022, including demographic characteristics, features of the primary lesion, surgical and pathological information and postoperative complications, and calculated the missing rate of each entry as well as the follow-up data. Results A total of 1682 patients with colon cancer were included in the analysis, in which 981 patients were male and 701 patients were female, with an average age of (62.75±11.97) years. The postoperative complication rate was 15.6% (263/1682). Among the data entries, demographic features such as sex, age, ethnic group as well as the pathologic staging were collected without missing. The relatively high-missing entries were the colonoscopy tumor site with a missing rate of 12.2%, followed by immunohistochemical information of mismatch repair with a missing rate of 8.0%. The missing rate of all 33 entries was distributed in 0-12.2%, of which 81.8% (27/33) were less than 1% and 93.9% (31/33) were less than 5%. As for follow-up data, the percentage of patients with complete missing follow-up was 1.7%, which meant 98.3% patients had available survival data. The 1-year, 2-year, 3-year, 4-year and 5-year follow-up rates of patients enrolled before July 2, 2020 (patients enrolled after this date did not have regular follow-up information in a uniform format due to data migration) were 55.02%, 70.96%, 72.02%, 65.42% and 70.91%, respectively, and the 2-year complete follow-up rate was 19.5%. Conclusion The low rate of missing statistical entries and the high follow-up rate of our center's database has certain reference value for database establishment, but there is still room for improvement in terms of continuous follow-up.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 μm at 30 weeks, 272.2 ± 83.9 μm at 38 weeks, and 306.2 ± 77.4 μm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 μm per week (95% confidence interval [CI], 13.6–16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 μm per week (95% CI, −1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 μm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 μm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective: To investigate the ameliorative effect of peptide AFYRW derived from tartary buckwheat protein against LPS-induced vascular endothelial injury. Methods: Lipopolysaccharide (LPS) was used to induce vascular endothelial injury in human umbilical vein endothelial cells (HUVECs). The cell counting kit-8 (CCK8) assay was used to detect the effect of AFYRW on cell proliferation. Western blot was used to evaluate the protein expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and phosphorylation of nuclear factor-κB (NF-κB) p65. An enzymatic assay was used to detect the changes in the content of nitric oxide (NO). Monocyte adhesion assay was used to detect the adhesiveness of HUVECs. Results: Peptide AFYRW significantly increased the survival activity of cells, decreased the relative protein expression of VCAM-1, ICAM-1, IL-6, TNF-α, and iNOS, reduced the content of NO, inhibited LPS-induced adhesion of human monocyte THP-1 cells to HUVECs and suppressed the activity of NF-κB. Conclusion: Peptide AFYRW can ameliorate LPS-induced inflammation in HUVECs, which may be related to the inhibition of NF-κB activity.

Abstract Acute liver failure (ALF) is a life‐threatening condition. Cell‐based and cell‐free‐based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)‐based bioartificial liver (hUCMSC‐BAL), which is a simple and efficient strategy for ALF. D‐galactosamine‐based pig and mouse ALF models were used to explore the effectiveness of hUCMSC‐BAL and hUCMSC‐sEV therapies. Furthermore, high‐throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR‐139‐5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC‐BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC‐sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC‐sEV miRNA transcriptome analysis showed that miR‐139‐5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR‐139‐5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC‐BAL can inhibit cytokine storms and cell apoptosis through the sEV miR‐139‐5p/PDE4D axis. Therefore, we propose hUCMSC‐BAL as a therapeutic strategy for patients with early ALF.

Abstract Background Mammalian cells have three types of RNA polymerases (Pols), Pol I, II, and III. However, the extent to which these polymerases are cross-regulated and the underlying mechanisms remain unclear. Results We employ genome-wide profiling after acute depletion of Pol I, Pol II, or Pol III to assess cross-regulatory effects between these Pols. We find that these enzymes mainly affect the transcription of their own target genes, while certain genes are transcribed by the other polymerases. Importantly, the most active type of crosstalk is exemplified by the fact that Pol III depletion affects Pol II transcription. Pol II genes with transcription changes upon Pol III depletion are enriched in diverse cellular functions, and Pol III binding sites are found near their promoters. However, these Pol III binding sites do not correspond to transfer RNAs. Moreover, we demonstrate that Pol III regulates Pol II transcription and chromatin binding of the facilitates chromatin transcription (FACT) complex to alter local chromatin structures, which in turn affects the Pol II transcription rate. Conclusions Our results support a model suggesting that RNA polymerases show cross-regulatory effects: Pol III affects local chromatin structures and the FACT-Pol II axis to regulate the Pol II transcription rate at certain gene loci. This study provides a new perspective for understanding the dysregulation of Pol III in various tissues affected by developmental diseases.

As a transmission medium and heating energy, microwave is widely favored due to its high efficiency, strong selectivity, and easy control. Here, the effects of different heating methods (conventional thermal induction (CI) and microwave induction (MI)) on the polymerization rate of polycarboxylate superplasticizer (PCE) were investigated. Compared with CI, MI significantly boosted the polymerization rate (by approximately 51 times) and markedly decreased the activation energy (Ea), from 46.83 kJ mol−1 to 35.07 kJ mol−1. The polar of the monomers and initiators in the PCE synthesis contributes to varying permittivities and loss factors under the microwave field, which are influenced by their concentration and reaction temperature. The insights gained from the microwave thermal effects and the micro-kinetics of the PCE polymerization system are able to propose theoretical underpinnings for the industrial-scale application of microwave induction polymerization, potentially steering the synthesis of polymer materials towards a more efficient and cleaner process.

Beyond traditional endothelium-dependent vessel (EDV), vascular mimicry (VM) is another critical tumor angiogenesis that further forms in many malignant metastatic tumors. However, the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors, but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM. Here, we demonstrate a self-assembled nanoparticle (VE-DDP-Pro) featuring self-anti-EDV and -VM capacity enables to significantly enhance the treatment efficacy of cisplatin (DDP) against the growth and metastasis of ovarian cancer. The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles (VE) onto the surface of protamine (Pro) nanoparticle. We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE, which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF, AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT, facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer. Thus, combing with the chemotherapeutics effectiveness of DDP, the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer. We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

Background: Centella asiatica Linn Urban (CA) is a medicinal herb used in traditional medicine for its anti-inflammatory and antinociceptive properties. Feline species usually exhibit toxicity toward nonsteroidal anti-inflammatory drugs, and thus the analgesic potential of CA is worth investigating in domestic cats. Purpose: The objective of this study was to evaluate the efficacy of CA extract in oral formulation for controlling postoperative pain and inflammation in cats undergoing ovariohysterectomy. Study Design: Randomized, prospective, blind, placebo-controlled study. Methods: This study included 18 healthy female cats randomized into three groups: control, low-dose group (100 mg/kg), and high-dose group (200 mg/kg). Accordingly, subjects were given orally administered placebo jelly or CA mixed jelly 12 h before surgery and 4, 24, 48, and 72 h after surgery. Serum amyloid A (SAA) and white blood cell count (WBC) were tested 23 h after surgery. Postoperative pain was evaluated at 4, 8, 24, 48, and 72 h after extubation by using the UNESP-Botucatu multidimensional composite pain scale (UFEPS). Wound scores were assessed using an infrared thermal imaging camera and normal pictures token at right after the surgery and at 1, 2, and 3 days after the surgery. SAA and WBC values were compared between groups via ANOVA (p < 0.05). The Scheirer-Ray-Hare test was used to analyze the ordinal score: pain score and wound-healing score (p < 0.05). Results: The high-dose group had a significantly lower UFEPS score than the control group (p = 0.007). In the high-dose group, few cats had a high temperature at the surgical wound after surgery. The level of SAA, WBC, and wound scores showed no significant difference among groups. No adverse side effects were found after receiving the CA extract. Conclusion: CA extract powder can be used as an analgesic in domestic cats for preventing and treating postoperative pain. The dosage and frequency of CA oral administration should be further studied.

The main focus of this research work was to study the anti-cancer properties of 7,8-dihydromethysticin against HL-60 leukemia cells. Investigations were also performed to check its impact on the phases of the cell cycle, cell migration and invasion, JAK/STAT signalling pathway and intracellular mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Cell proliferation was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and effects on colony formation were examined via clonogenic assay. Flow cytometry and Western blott analysis were performed to investigate the distribution of cell cycle phases. Flow cytometric analysis was performed for the examination of MMP and ROS production. The effect on JAK/STAT signalling pathway was examined through Western blot analysis. Results depicted that 7,8-dihydromethysticin induced concentration- as well as time-dependent inhibition of cell proliferation in leukemia HL-60 cells. Clonogenic assay indicated potential suppression in leukemia HL-60 cell colonies. The 7,8-dihydromethysticin molecule also caused cell cycle arrest at G2/M-phase along with concentration-dependent inhibition of cyclin B1, D1 and E. ROS and MMP measurements indicated significant ROS enhancement and MMP suppression with increasing 7,8-dihydromethysticin concentrations. Additionally, 7,8-dihydromethysticin led to remarkable dose-reliant inhibition of cell invasion as well as cell migration. Therefore, 7,8-dihydromethysticin should be considered a valuable candidate for leukemia research and chemoprevention.

Purpose: To report a patient previously treated for primary and secondary syphilis who presented with papillitis. The patient was found to have neurosyphilis likely due to inadequate treatment of primary and secondary syphilis. Observations: A 60-year-old male with human immunodeficiency virus (HIV) and hepatitis C was referred for evaluation of blurry vision for the past several months. Anterior segment examination was notable for 1+ diffuse non-granulomatous keratic precipitates and 2+ flare with trace cell in both eyes. Dilated fundus exam revealed grade 2 optic disc edema in both eyes with no evidence of infectious retinitis. He was recently treated for syphilis with a single dose of intramuscular (IM) penicillin. These findings were consistent with syphilitic papillitis likely secondary to neurosyphilis. The patient underwent a lumbar puncture which confirmed the diagnosis of neurosyphilis. He was admitted to the hospital for intravenous (IV) penicillin. He later revealed a prior history of syphilis that was treated 3 years ago and 1 year ago. Conclusions and importance: Ocular syphilis can have a wide variety of presentations. Any patient with syphilis and uveitis should have prompt work up for neurosyphilis. Patients with any stage of syphilis need close follow up with repeat titers after treatment to ensure adequate treatment and prevent progression and permanent ocular or neurologic sequelae.

During a parasitological survey of goldfish Carassius auratus (Linnaeus, 1758) in China, two myxosporeans were collected in the present study including a Thelohanellus species and a Myxobolus species. To identified the two myxosporeans, a morphological, histological and molecular study was performed. The Thelohanellus species was characterized by round, white plasmodia in fins of goldfish. Compared with all described Thelohanellus species, spore morphology of the Thelohanellus species in the present study was distinct from them. BLAST search showed that SSU rDNA sequence of this Thelohanellus species did not match any sequence in GenBank database. Phylogenetically, the Thelohanellus species obtained in the present study was sister to Thelohanellus nikolskii Achmerov, 1955. So, the present Thelohanellus species was identified as a novel species and named Thelohanellus pseudonikolskii n. sp. The Myxobolus species was characterized by a number of round or irregularly shaped, white plasmodia in gills of goldfish. When compared with all reported Myxobolus species, spore morphology of the present Myxobolus species was most similar to Myxobolus koi Kudo, 1920. Histological analysis showed that plasmodia of this Myxobolus species simultaneously developed in stratified epithelium of filament and in lamellae, which was same to M. koi. Moreover, BLAST search showed that SSU rDNA sequence of the present Myxobolus species was identical to M. koi. Thus, the morphological, histological and molecular analysis demonstrated that the present Myxobolus species was conspecific with M. koi. Due to M. koi consistently described from gills of common carp Cyprinus carpio Linnaeus, 1758 and koi carp C. carpio in the previous researches, M. koi was first found to infect gills of goldfish in the present study. Considering koi carp and goldfish both as ornamental fish frequently cultured together in China, the possible host shift of M. koi from koi carp to goldfish is of interest for further investigation.

The time maintenance accuracy of the navigation constellation determines the user positioning and timing performance. Especially in autonomous operation scenarios, the performance of navigation constellation maintenance time directly affects the duration of constellation autonomous navigation. Among them, the frequency stability of the atomic clock onboard the navigation satellite is a key factor. In order to further improve the stability of the navigation constellation time-frequency system, combined with the development of high-precision inter-satellite link measurement technology, the idea of constructing constellation-level synthetic atomic time has gradually become the development trend of major GNSS systems. This paper gives a navigation constellation time scale generation framework, and designs an improved Kalman plus weights (KPW) time scale algorithm and time-frequency steer algorithm that integrates genetic algorithms. Finally, a 30-day autonomous timekeeping simulation was carried out using the GPS precision clock data provided by CODE, when the sampling interval is 300 s, the Allan deviation of the output time scale is 5.73 × 10−14, a 71% improvement compared with the traditional KPW time scale algorithm; when the sampling interval is 1 day, the Allan deviation is 9.17 × 10−15; when the sampling interval is 1 × 106 s, the Allan deviation is 8.87 × 10−16, a 94% improvement compared with the traditional KPW time scale algorithm. The constellation-level high-precision time scale generation technology proposed in this paper can significantly improve the stability performance of navigation constellation autonomous timekeeping.

Abstract Drug-induced liver injury (DILI) is one of the leading causes of clinical trial failures and high drug attrition rates. Currently, the commonly used hepatocyte models include primary human hepatocytes (PHHs), animal models, and hepatic cell lines. However, these models have disadvantages that include species-specific differences or inconvenient cell extraction methods. Therefore, a novel, inexpensive, efficient, and accurate model that can be applied to drug screening is urgently needed. Owing to their self-renewable ability, source abundance, and multipotent competence, stem cells are stable sources of drug hepatotoxicity screening models. Because 3D culture can mimic the in vivo microenvironment more accurately than can 2D culture, the former is commonly used for hepatocyte culture and drug screening. In this review, we introduce the different sources of stem cells used to generate hepatocyte-like cells and the models for hepatotoxicity testing that use stem cell-derived hepatocyte-like cells.

Ceria-zirconia-alumina composite oxides CZxA (the molar ratios of Ce, Zr and Al are 1:x:2, x=0, 0.5, 1, 1.5 and 2) fresh samples were prepared by the co-precipitation method. The samples were thermally aged in a flowing air atmosphere and in 10% H2/Ar flow. The structure and performance of the composite oxides were studied by X-ray powder diffraction (XRD), N2 adsorption-desorption (BET), oxygen storage capacity (OSC) measurements, and H2 temperature-programmed reduction (H2-TPR). The results show that for CZxA samples, with the increase of the content of Zr, no CeAlO3 phase is observed in the CZ1.5A-H2-1100 and CZ2A-H2-1100 samples which are reductively aged at 1100 ℃; the oxygen storage capacity (OSC) is 713 μmol·g-1 and 548 μmol·g-1, respectively, far higher than the 23 μmol·g-1 of CZA-H2-1100; and the hydrogen consumption of H2-TPR is 1995 μmol·g-1 and 2087 μmol·g-1, respectively, while the hydrogen consumption of CZA-H2-1100 was significantly reduced to 310 μmol·g-1. The OSC of CZxA is affected by the formation of CeAlO3 during the reductive treatment, which is consistent with the change result of the hydrogen consumption of H2-TPR. It was found that CA samples are more likely to produce CeAlO3 after reductive treatment, and the CZ1.5A and CZ2A samples doped with a certain amount of Zr elements in CA can inhibit the formation of CeAlO3, thus significantly improve the oxygen storage performance and the hydrogen consumption of H2-TPR of the material. Furthermore, CZxA have better reduction performance at low temperature after reductive treatment.

A ruthenium-catalyzed electrochemical dehydrogenative C(sp2)−H acyloxylation of aniline derivatives with carboxylic acids has been developed. Electric current is used to recycle the active ruthenium-based catalyst and promote H2 evolution. This method significantly expands the scope and enhances the selectivity of metal-electron catalyzed mono- and di-acyloxylations, which remain challenged. Our findings allowed mono-selectivity in broadly effective late-stage diversification of structurally complex drugs and natural product molecules, tolerating drugs, natural products and amino acids. The method and its underlying strategy are expected to have widespread uses in functional aniline synthesis and drug discovery process.

We consider an elliptic variational-hemivariational inequality 𝓟 in a reflexive Banach space, governed by a set of constraints K, a nonlinear operator A, and an element f. We associate to this inequality a sequence {𝓟n} of variational-hemivariational inequalities such that, for each n ∈ ℕ, inequality 𝓟n is obtained by perturbing the data K and A and, moreover, it contains an additional term governed by a small parameter εn. The unique solvability of 𝓟 and, for each n ∈ ℕ, the solvability of its perturbed version 𝓟n, are guaranteed by an existence and uniqueness result obtained in literature. Denote by u the solution of Problem 𝓟 and, for each n ∈ ℕ, let un be a solution of Problem 𝓟n. The main result of this paper states the strong convergence of un → u in X, as n → ∞. We show that the main result extends a number of results previously obtained in the study of Problem 𝓟. Finally, we illustrate the use of our abstract results in the study of a mathematical model which describes the contact of an elastic body with a rigid-deformable foundation and provide the corresponding mechanical interpretations.

Abstract Background Mesenchymal stem cells (MSCs) are considered to be an effective tool for regenerative medicine with promising applications for clinical therapy. However, incongruent data has been reported partially owing to their functional heterogeneity. To provide sufficient and suitable clinical seed cells derived from the placenta for MSC therapy, we compared the various current isolation methods, as well as the biological characteristics, of different human placenta mesenchymal stem cells (hPMSCs). Methods We selected placentas from 35 informed donors and exploited three commonly used methods. MSCs were isolated from different parts of placental tissue including umbilical cord (UC), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV), and deciduae (DC). The appropriate isolation methods for each type of hPMSCs were first assessed. The resulting five MSC types from the same individuals were identified based on their surface marker expression, proliferation capacity, transcriptome, differentiation, multipotency and karyotype. Results All three methods successfully isolated the five hPMSC types from placental tissues. However, the UC-MSCs were most effectively separated via the tissue explant method, while the enzymatic digestion method was found to be more suitable for separating CV-MSCs, owing to its higher output efficiency compared to the other methods. Alternatively, the perfusion method was complicated and exhibited the lowest efficiency for cell isolation and uniformity. Furthermore, we determined that UC-MSCs and CV-MSCs express a higher level of paracrine cytokines and display much stronger proliferative capacity as well as superior extraction efficiency. Finally, karyotype analysis revealed that DC-MSCs are derived from the mother, while the other cell types are derived from the fetus. Moreover, the different hPMSCs exhibited unique gene expression profiles, which may prove advantageous in treatment of a broad range of diseases. Conclusions hPMSCs from different sources are similar yet also unique. Our results describe the biological characteristics of five hPMSCs and provide insights to aide in the selection process of candidates for MSCs treatment. Overall, UC- and CV-MSCs appear to be ideal sources of primary MSCs for clinical treatment and future research.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Two parasitoids, Metapelma beijingense Yang (Hymenoptera, Eupelmidae) and Spathius ochus Nixon (Hymenoptera, Braconidae) are redescribed and illustrated. Both were reared from Coraebus cavifrons Descarpentries & Villiers (Coleoptera, Buprestidae) boring in Symplocos stellaris Brand (Symplocaceae). Metapelma beijingense is a solitary parasitoid with a parasitism rate of about 13.5% and S. ochus is a gregarious parasitoid with a parasitism rate of about 21.2%. A revised key to Oriental and Palaearctic species of Metapelma Westwood and a key to the species of the Spathius labdacus-group are provided.

BackgroundIdentifying the metabolite profile of individuals with prediabetes who turned to type 2 diabetes (T2D) may give novel insights into early T2D interception. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population.MethodsWe used an untargeted metabolomics approach to investigate the associations between serum metabolites and risk of prediabetes who turned to overt T2D (n=153, mean follow up 5 years) in a Chinese population (REACTION study). Results were compared with matched controls who had prediabetes at baseline [age: 56 ± 7 years old, body mass index (BMI): 24.2 ± 2.8 kg/m2] and at a 5-year follow-up [age: 61 ± 7 years old, BMI: 24.5 ± 3.1 kg/m2]. Confounding factors were adjusted and the associations between metabolites and diabetes risk were evaluated with multivariate logistic regression analysis. A 10-fold cross-validation random forest classification (RFC) model was used to select the optimal metabolites panels for predicting the development of diabetes, and to internally validate the discriminatory capability of the selected metabolites beyond conventional clinical risk factors.FindingsMetabolic alterations, including those associated with amino acid and lipid metabolism, were associated with an increased risk of prediabetes progressing to diabetes. The most important metabolites were inosine [odds ratio (OR) = 19.00; 95% confidence interval (CI): 4.23-85.37] and carvacrol (OR = 17.63; 95% CI: 4.98-62.34). Thirteen metabolites were found to improve T2D risk prediction beyond eight conventional T2D risk factors [area under the curve (AUC) was 0.98 for risk factors + metabolites vs 0.72 for risk factors, P < 0.05].InterpretationsUse of the metabolites identified in this study may help determine patients with prediabetes who are at highest risk of progressing to diabetes.

Abnormal heart rhythm is a common cardiac dysfunction in obese patients, and its pathogenesis is related to systemic lipid accumulation. The cardiomyocyte-derived apoLpp (homologous gene in Drosophila of the human apolipoprotein B) plays an important role in whole-body lipid metabolism of Drosophila under a high-fat diet (HFD). Knockdown of apoLpp derived from cardiomyocytes can reduce HFD-induced weight gain and abdominal lipid accumulation. In addition, exercise can reduce the total amount of apoLpp in circulation. However, the relationship between regular exercise, cardiomyocyte-derived apoLpp and abnormal heart rhythm is unclear. We found that an HFD increased the level of triglyceride (TG) in the whole-body, lipid accumulation and obesity in Drosophila. Moreover, the expression of apoLpp in the heart increased sharply, the heart rate and arrhythmia index increased and fibrillation occurred. Conversely, regular exercise or cardiomyocyte-derived apoLpp knockdown reduced the TG level in the whole-body of Drosophila. This significantly reduced the arrhythmia induced by obesity, including the reduction of heart rate, arrhythmia index, and fibrillation. Under HFD conditions, flies with apoLpp knockdown in the heart could resist the abnormal cardiac rhythm caused by obesity after receiving regular exercise. HFD-induced obesity and abnormal cardiac rhythm may be related to the acute increase of cardiomyocyte-derived apoLpp. Regular exercise and inhibition of cardiomyocyte-derived apoLpp can reduce the HFD-induced abnormal cardiac rhythm.

Formalin‐fixed, paraffin‐embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)‐SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B‐cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh‐frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.

Braconid parasitoids reared from Malus sieversii and Malus domestica trees in NW China infested by Agrilus mali Matsumura (Coleoptera, Buprestidae) are illustrated and discussed. Six species were found parasitising Agrilus mali in NW China, namely, Atanycolus ivanowi (Kokujev) (Braconinae), Doryctes undulatus (Ratzeburg), Pareucorystes varinervis Tobias, Polystenus rugosus Foerster, Spathius sinicus Chao, and Spathius brevicaudis Ratzeburg (Doryctinae). All listed species are newly recorded parasitoids of Agrilus mali. Pareucorystes varinervis and Spathius brevicaudis are new records for the Chinese fauna, but Spathius brevicaudis has been recorded from Taiwan before. Both sexes of Spathius brevicaudis are redescribed here to allow inclusion in the recent revision of the Chinese Spathius species. An identification key to the six braconid parasitoids of Agrilus mali in NW China is provided.