Chiral molecular intercalation superlattices.

The discovery of chiral-induced spin selectivity (CISS) opens up the possibility to manipulate spin orientation without external magnetic fields and enables new spintronic device designs1-4. Although many approaches have been explored for introducing CISS into solid-state materials and devices, the resulting systems so far are often plagued by high inhomogeneity, low spin selectivity or limited stability, and have difficulties in forming robust spintronic devices5-8. Here we report a new class of chiral molecular intercalation superlattices (CMIS) as a robust solid-state chiral material platform for exploring CISS. The CMIS were prepared by intercalating layered two-dimensional atomic crystals (2DACs) (such as TaS2 and TiS2) with selected chiral molecules (such as R-α-methylbenzylamine and S-α-methylbenzylamine). The X-ray diffraction and transmission electron microscopy studies demonstrate highly ordered superlattice structures with alternating crystalline atomic layers and self-assembled chiral molecular layers. Circular dichroism studies show clear chirality-dependent signals between right-handed (R-) and left-handed (S-) CMIS. Furthermore, by using the resulting CMIS as the spin-filtering layer, we create spin-selective tunnelling junctions with a distinct chirality-dependent tunnelling current, achieving a tunnelling magnetoresistance ratio of more than 300 per cent and a spin polarization ratio of more than 60 per cent. With a large family of 2DACs of widely tunable electronic properties and a vast selection of chiral molecules of designable structural motifs, the CMIS define a rich family of artificial chiral materials for investigating the CISS effect and capturing its potential for new spintronic devices.

Genetic diversity and population structure of wheat landraces in Southern Winter Wheat Region of China.

BACKGROUND: Wheat landraces are considered a valuable source of genetic diversity for breeding programs. It is useful to evaluate the genetic diversity in breeding studies such as marker-assisted selection (MAS), genome-wide association studies (GWAS), and genomic selection. In addition, constructing a core germplasm set that represents the genetic diversity of the entire variety set is of great significance for the efficient conservation and utilization of wheat landrace germplasms. RESULTS: To understand the genetic diversity in wheat landrace, 2,023 accessions in the Jiangsu Provincial Crop Germplasm Resource Bank were used to explore the molecular diversity and population structure using the Illumina 15 K single nucleotide polymorphism (SNP) chip. These accessions were divided into five subpopulations based on population structure, principal coordinate and kinship analysis. A significant variation was found within and among the subpopulations based on the molecular variance analysis (AMOVA). Subpopulation 3 showed more genetic variability based on the different allelic patterns (Na, Ne and I). The M strategy as implemented in MStratv 4.1 software was used to construct the representative core collection. A core collection with a total of 311 accessions (15.37%) was selected from the entire landrace germplasm based on genotype and 12 different phenotypic traits. Compared to the initial landrace collections, the core collection displayed higher gene diversity (0.31) and polymorphism information content (PIC) (0.25), and represented almost all phenotypic variation. CONCLUSIONS: A core collection comprising 311 accessions containing 100% of the genetic variation in the initial population was developed. This collection provides a germplasm base for effective management, conservation, and utilization of the variation in the original set.

New Sight of Renal Toxicity Caused by UV-Aged Polystyrene Nanoplastics: Induced Ferroptosis via Adsorption of Transferrin.

Secondary nanoplastics (NPs) caused by degradation and aging due to environmental factors are the main source of human exposure, and alterations in the physicochemical and biological properties of NPs induced by environmental factors cannot be overlooked. In this study, pristine polystyrene (PS) NPs to obtain ultraviolet (UV)-aged PS NPs (aPS NPs) as secondary NPs is artificially aged. In a mouse oral exposure model, the nephrotoxicity of PS NPs and aPS NPs is compared, and the results showed that aPS NPs exposure induced more serious destruction of kidney tissue structure and function, along with characteristic changes in ferroptosis. Subsequent in vitro experiments revealed that aPS NPs-induced cell death in human renal tubular epithelial cells involved ferroptosis, which is supported by the use of ferrostatin-1, a ferroptosis inhibitor. Notably, it is discovered that aPS NPs can enhance the binding of serum transferrin (TF) to its receptor on the cell membrane by forming an aPS-TF complex, leading to an increase in intracellular Fe2+ and then exacerbation of oxidative stress and lipid peroxidation, which render cells more sensitive to ferroptosis. These findings indicated that UV irradiation can alter the physicochemical and biological properties of NPs, enhancing their kidney biological toxicity risk by inducing ferroptosis.

Mn(II) Promoted Divergent-Convergent Domino Reaction Giving Dinuclear Tetrasubstituted Pyrrole Complex.

Domino reaction of benzo[d]thiazole-2-methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P-=2,3,4,5-tetrakis(benzo[d]thiazol-2-yl)pyrrol-1-ide). The reaction process has been studied by assigning a series of intermediates based on time-dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent-convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1-(benzo[d]thiazol-2-yl)-N-(benzo[d]thiazol-2-ylmethyl)methanimine) and alkene C (1,2-bis(benzo[d]thiazol-2-yl)ethene) through oxidative self-condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C-C bonds and one C-N bond are formed through this six-step domino sequence. The corresponding organic skeleton (HP: 2,2',2'',2'''-(1H-pyrrole-2,3,4,5-tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4-diphenyl substituted analogue 2,2'-(3,4-diphenyl-1H-pyrrole-2,5-diyl)bis(benzo[d]thiazole) (DPB) (42 %).

Iron Deposition in Parkinson's Disease: A Mini-Review.

Iron deposition is crucial pathological changes observed in patients with Parkinson's disease (PD). Recently, scientists have actively explored therapeutic approaches targeting iron deposition in PD. However, several clinical studies have failed to yield consistent results. In this review, we provide an overview of iron deposition in PD, from both basic research and clinical perspectives. PD patients exhibit abnormalities in various iron metabolism-related proteins, leading to disruptions in iron distribution, transport, storage, and circulation, ultimately resulting in iron deposition. Excess iron can induce oxidative stress and iron-related cell death, and exacerbate mitochondrial dysfunction, contributing to the progression of PD pathology. Magnetic resonance imaging studies have indicated that the characteristics of iron deposition in the brains of PD patients vary. Iron deposition correlates with the clinical symptoms of PD, and patients with different disease courses and clinical presentations display distinct patterns of iron deposition. These iron deposition patterns may contribute to PD diagnosis. Iron deposition is a promising target for PD treatment. However, further research is required to elucidate the underlying mechanisms and their impacts on PD.

Single-Cell Molecular Profiling of Head and Neck Squamous Cell Carcinoma Reveals Five Dysregulated Signaling Pathways Associated With Circulating Tumor Cells.

OBJECTIVES: To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization. INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) has a significant global burden and is a disease with poor survival. Despite trials exploring new treatment modalities to improve disease control rates, the 5 year survival rate remains low at only 60%. Most cancer malignancies are reported to progress to a fatal phase due to the metastatic activity derived from treatment-resistant cancer cells, regarded as one of the most significant obstacles to develope effective cancer treatment options. However, the molecular profiles of cancer cells have not been thoroughly studied. METHODS: Here, we examined in-situ HNSCC tumors and pairwisely followed up with the downstream circulating tumor cells (CTCs)-based on the surrogate biomarkers to detect metastasis that is established in other cancers - not yet being fully adopted in HNSCC treatment algorithms. RESULTS: Specifically, we revealed metastatic HNSCC patients have complex CTCs that could be defined through gene expression and mutational gene profiling derived from completed single-cell RNASeq (scRNASeq) that served to confirm molecular pathways inherent in these CTCs. To enhance the reliability of our findings, we cross-validated those molecular profiles with results from previously published studies. CONCLUSION: Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.

ObjectivesInvestigating the dysregulated signaling pathways of head and neck squamous cell carcinoma (HNSCC) linked with circulating tumor cells (CTCs) using single-cell molecular characterization.IntroductionHNSCC poses a significant global health burden with poor survival rates despite advancements in treatment. Metastatic activity from treatment-resistant cancer cells remains a major challenge in developing effective treatments. However, the molecular profiles of cancer cells, particularly CTCs, are not well-understood.MethodsWe analyzed in-situ HNSCC tumors and corresponding CTCs using surrogate biomarkers to detect metastasis, a technique not widely used in HNSCC treatment protocols.ResultsOur study revealed complex CTCs in metastatic HNSCC patients characterized by gene expression and mutational gene profiling via single-cell RNASeq (scRNASeq). These profiles confirmed molecular pathways inherent in CTCs, further validated by previous research.ConclusionThrough our research, we identified five dysregulated signaling pathways in CTCs, suggesting potential biomarker panels for HNSCC screening in situ tumors.

Design, synthesis and activity evaluation of quinolinone derivatives as EZH2 inhibitors.

The enhancer of zeste homologue 2 (EZH2) is the core catalytic subunit of polycomb repressive complex 2, which catalyzes lysine 27 methylation of histone H3. Herein, a series of quinolinone derivatives were designed and synthesized based on the structure of Tazemetostat as the lead compound. Compound 9l (EZH2WT IC50 = 0.94 nM) showed stronger antiproliferative activity in HeLa cells than the lead compound. Moreover, compound 9e (EZH2WT IC50 = 1.01 nM) significantly inhibited the proliferation and induced apoptosis in A549 cells.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Effect of concomitant tricuspid annuloplasty on postoperative wound complications in heart failure patients undergoing mitral valve repair.

Tricuspid valve repair (TVR) combined with mitral valve surgery (MVS) has been a controversial issue. It is not clear whether the combined surgery has any influence on the occurrence of postoperative complications. The aim of this study was to compare the occurrence of complications including wound infection, wound bleeding, and mortality after MVS combined with or without TVR. By meta-analysis, a total of 1576 papers were collected from 3 databases, and 7 of them were included. We provided the necessary data of 7 included studies such as the authors, publication date, country, surgical approach and case number, patient age, and so on. Statistical analysis was carried out with RevMan 5.3 software. We found that patients with heart failure accepting MVS combined with or without TVR, performed no statistically significant difference in postoperative wound infection (OR: 0.88; 95% CI: 0.29, 2.62; P = 0.81), wound bleeding (OR: 0.74; 95% CI: 0.3, 1.48; P = 0.39), and mortality (OR: 1.05; 95% CI: 0.42, 2.61; P = 0.92). In conclusion, current evidence indicated that the combined surgery had no additional risk of postoperative complications, and might be an effective alternative surgical approach to mitral valve diseases accompany with tricuspid regurgitation. However, for the limited case size, it was required to support the findings with a large number of cases in further studies.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Highly Selective Electrochemical Reduction of CO2 into Methane on Nanotwinned Cu.

The electrochemical carbon dioxide reduction reaction (CO2RR) is a promising route to close the carbon cycle by reducing CO2 into valuable fuels and chemicals. Electrocatalysts with high selectivity toward a single product are economically desirable yet challenging to achieve. Herein, we demonstrated a highly (111)-oriented Cu foil electrocatalyst with dense twin boundaries (TB) (tw-Cu) that showed a high Faradaic efficiency of 86.1 ± 5.3% toward CH4 at -1.2 ± 0.02 V vs the reversible hydrogen electrode. Theoretical studies suggested that tw-Cu can significantly lower the reduction barrier for the rate-determining hydrogenation of CO compared to planar Cu(111) under working conditions, which suppressed the competing C-C coupling, leading to the experimentally observed high CH4 selectivity.

RNA-Sequencing Combined With Genome-Wide Allele-Specific Expression Patterning Identifies ZNF44 Variants as a Potential New Driver Gene for Pediatric Neuroblastoma.

INTRODUCTION: Neuroblastoma (NB) is one of the children's most common solid tumors, accounting for approximately 8% of pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in several genes, such as ALK, have been associated with NB progression and can facilitate the discovery of novel therapeutic strategies. However, the differential expression of mutated and wild-type alleles on the transcriptome level is poorly studied. METHODS: This study analyzed 219 whole-exome sequencing datasets with somatic mutations detected by MuTect from paired normal and tumor samples. RESULTS: We prioritized mutations in 8 candidate genes (RIMS4, RUSC2, ALK, MYCN, PTPN11, ALOX12B, ZNF44, and CNGB1) as potential driver mutations. We further confirmed the presence of allele-specific expression of the somatic mutations in NB with integrated analysis of 127 RNA-seq samples (of which 85 also had DNA-seq data available), including MYCN, ALK, and PTPN11. The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on the clinical outcomes of tumors. CONCLUSION: Our study suggests 2 novel variants of ZNF44 as a novel candidate driver gene for NB.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics unveils the metabolic alterations in colon cancer mice during CT-guided radiofrequency ablation.

Colon cancer (CC) is a malignancy of the digestive tract, and computed tomography (CT)-guided radiofrequency ablation (RFA) has been extensively adopted in cancer treatment. We aimed to explore the changes in fecal metabolism after CT-guided RFA in CC mice. The orthotopic CC mice received CT-guided RFA upon modeling. Subsequently, we quantified tumor volumes and weights to assess treatment efficacy. Next, because metabolomics is useful for evaluating therapeutic validity, feces were collected for metabolomics analysis. CT-guided RFA inhibited tumor growth effectively. Additionally, metabolomics results showed that the contents of bile acids and fatty acids were downregulated in CC mouse feces. Moreover, the levels of amino acids and carbohydrates were decreased while the levels of fatty acids, organic acids, phenols, pyridines and short-chain fatty acids were elevated in feces after CC mice received CT-guided RFA. Pathway enrichment analysis revealed that those differential metabolites were closely related to fatty acids degradation and synthesis. CT-guided RFA possesses a strong ability to suppress CC development in mice, accompanied by a significant increase of fatty acid content in feces. This study proposes a novel approach and target for CC treatment, which provides hope for CC patients and establishes a solid basis for future in-depth studies.

Designed bacteria based on natural pbr operons for detecting and detoxifying environmental lead: A mini-review.

Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.

Chronic and intergenerational toxic effects of 1-decyl-3-methylimidazolium hexafluorophosphate on the water flea, Moina macrocopa.

With the increasing use and production of "green solvents" ionic liquids (ILs) and their known stability in the environment, the potential adverse effects of ILs have become a focus of research. In the present study, acute, chronic, and intergenerational toxic effects of an imidazolium-based ionic liquid, 1-decyl-3-methylimidazolium hexafluorophosphate ([Demim]PF6), on Moina macrocopa were investigated following the parental exposure. The results showed that [Demim]PF6 exhibited high toxicity to M. macrocopa, and the long-term exposure significantly inhibited the survivorship, development, and reproduction of the water flea. Furthermore, it is also observed that [Demim]PF6 induced toxic effects in the following generation of M. macrocopa, resulting in the complete cessation of reproduction in the first offspring generation, and the growth of the organisms was also significantly affected. These findings provided a novel insight into the intergenerational toxicity induced by ILs to crustaceans and suggested that these compounds pose potential risks to the aquatic ecosystem.

Sirolimus improves the prognosis of liver recipients with hepatocellular carcinoma: A single-center experience.

BACKGROUND: Tumor recurrence after liver transplantation (LT) for selective patients diagnosed with hepatocellular carcinoma (HCC) in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients. The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients. METHODS: The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed. These patients were divided into the sirolimus group [patients took sirolimus combined with calcineurin inhibitors (CNIs) (n = 125)] and non-sirolimus group [patients took CNI-based therapy without sirolimus (n = 68)]. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. The prognostic factors and independent risk factors for RFS and OS were further evaluated. RESULTS: Non-sirolimus was an independent risk factor for RFS (HR = 2.990; 95% CI: 1.050-8.470; P = 0.040) and OS (HR = 3.100; 95% CI: 1.190-8.000; P = 0.020). A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group (69.6% vs. 80.9%, P = 0.030). Compared with the non-sirolimus group, the sirolimus group had significantly better RFS (P < 0.001) and OS (P < 0.001). Further subgroup analysis showed similar results. CONCLUSIONS: This study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.

Marginal donor liver versus standard donor liver: A single-center observational study.

BACKGROUND: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). METHODS: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. RESULTS: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation (P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT (P > 0.05); there was also no significant difference in the survival curve (P = 0.335). CONCLUSIONS: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.

Growth, Reproduction, and Transgenerational Effects of Kinoprene on Moina macrocopa.

Juvenile hormone analogues (JHAs) are a kind of effective insecticide. These compounds have relatively low toxicity for fish, birds, and mammals, so they are increasingly used in insect pest control. However, JHAs may cause various adverse effects in crustaceans as in insects, because they have a close evolutionary relationship and possess similar juvenile hormone systems. To date, the chronic toxicities of JHAs over generations lacked intensive investigation. The present study evaluated the acute, chronic, and transgenerational effects of a terpenoid JHA, kinoprene, using the water flea Moina macrocopa. The result of acute exposure shows that kinoprene exhibited high toxicity to M. macrocopa. The chronic results indicate that kinoprene inhibited the survivorship, development, and reproduction of the organism. Moreover, the adverse effects induced by kinoprene continued in the F2 generation with no direct exposure but recovered in the F3 generation.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.