Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Functional roles of nicotinic acetylcholine receptors in dinotefuran and flupyrimin toxicity and their sublethal effects on Sogatella furcifera (Hemiptera: Delphacidae).

Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), a serious rice pest, has developed significant resistance to a wide range of pesticides. Neonicotinoid insecticides are currently the primary choice for controlling S. furcifera, yet their impact on the species remains poorly understood. In this study, we investigated the binding sites of a conventional insecticide (dinotefuran) and a novel insecticide (flupyrimin), and evaluated their sublethal effects on S. furcifera. Our results revealed that the LC50 of dinotefuran and flupyrimin were 2.51 mg/L and 2.80 mg/L in third-instar S. furcifera, respectively. RNA interference (RNAi) knockdown of S. furcifera nicotinic acetylcholine receptor (nAChR) alpha2 subunit (Sfα2) and S. furcifera nAChR beta1 subunit (Sfß1) significantly reduced the susceptibility to dinotefuran by 18.7% and 16.8%, respectively, but had no effect on flupyrimin. Reproduction of the F0 and F1 generations was significantly inhibited by the LC25 of both dinotefuran and flupyrimin. In the dinotefuran treatment at LC25, the intrinsic growth rate (r) and finite growth rate (λ) were reduced to 0.15 and 0.16 days, respectively; the mean generation time (T) increased to 27.77 days, and the relative fitness was only 0.76 compared to the control. Additionally, the relative fitness (Rf) of the flupyrimin-treated group was reduced to 0.93 and 0.86 times that of the control group. The population dynamics of S. furcifera are significantly affected by both dinotefuran and flupyrimin, making these insecticides valuable tools for integrated pest management and the rational use of insecticides.

Effects of soil properties and microbial community composition on ginsenosides accumulation in farmland ginseng.

Soil is the material basis of ginseng survival, and revealing the correlation between soil and ginsenoside has far-reaching significance for the sustainable development of ginseng industry. In this study, the content of ginsenosides in 3-year-old ginseng roots, the physicochemical properties of rhizosphere soil and the microbial community composition were studied. The results showed that the contents of total saponins in different months were significantly different. The richness and diversity of soil microbial community decreased with the extension of planting time. The activities of complexed iron, organic matter and protease in soil had significant effects on α-diversity of soil microbial community. Functional gene analysis showed that carbon sequestration, protein translation, nitrogen metabolism, transcription factors and chlorophyll metabolism were the main functions of soil bacterial community. The results of correlation analysis and redundancy analysis showed that pH, available potassium, organic matter, complexed iron, Firmicutes and Acidobacteria were the key factors affecting ginsenoside accumulation. The changes of soil physical and chemical properties affect the abundance of soil microorganism, and the accumulation of ginsenoside in ginseng is affected by soil microorganism. A co-regulatory network of Physicochemical Properties-Microbe-Ginsenoside was established. To provide theoretical support for the cultivation of ginseng.

Storage protein SfSP8 mediates larval starvation tolerance of Spodoptera frugiperda.

BACKGROUND: Energy homeostasis is vital for insects to survive food shortages. This study investigated the starvation tolerance of Spodoptera frugiperda, which invaded China in 2019, focusing on its storage protein family, crucial for energy balance. 10 storage protein family members were identified and their expression patterns at different development stages and under different starvation stress were analyzed. METHODS AND RESULTS: We used qPCR to evaluate the expression levels of storage protein family members under various larval instars and starvation conditions. We discovered that, among above 10 members, only 2 storage proteins, SfSP8 and SfSP7 showed significant upregulation in response to starvation stress. Notably, SfSP8 upregulated markedly after 24 h of fasting, whereas SfSP7 exhibited a delayed response, with significant upregulation observed only after 72 h of starvation. Then we significantly reduced the starvation tolerance of larvae through RNAi-mediated knockdown of SfSP8 and also altered the starvation response of SfSP7 from a late to an early activation pattern. Finally, we constructed transgenic Drosophila melanogaster with heterologous overexpressing SfSP8 revealed that the starvation tolerance of the transgenic line was significantly stronger than that of wild-type lines. CONCLUSIONS: SfSP8 was the core storage protein member that mediated the starvation tolerance of larvae of S. frugiperda. Our study on the novel function of storage proteins in mediating larval starvation tolerance of S. frugiperda is conducive to understanding the strong colonization of this terrible invasive pest.

Genetic diversity analysis of Saccharosydne procerus in Hunan region, China.

BACKGROUND: Saccharosydne procerus serves as a significant alternative host for parasitoids of the important rice pest, rice planthoppers. Rearing S. procerus on the water bamboo plants near rice field can provide a parasitic site for parasitic wasps during the idle period of rice fields, thereby stabilizing the number of parasitoids and suppressing the number of rice planthoppers in the field. However, limited understanding of genetic diversity of S. procerus restricts its application. Therefore, this study aims to analyze the genetic diversity of S. procerus in Hunan region. METHODS: In this study, 16 geographical populations of the S. procerus from the Hunan region were used. After screening, ISSR primers were employed for polymorphism detection. POPGENE32 software was used for genetic diversity analysis, and UPGMA clustering was applied for statistical analysis of different geographical populations to generate an evolutionary tree. RESULTS: Eleven ISSR primers were screened, resulting in the detection of 194 amplification locus, of which 126 were polymorphic. The average percentage of polymorphic locus was 64.95%. The mean Nei's gene diversity (H) was 0.2475, the mean Shannon's Information index (I) was 0.3708, and the Genetic diversity index among populations (Gst) was 0.3800. Cluster analysis identified three groups, with most populations concentrated in the second group, indicating no clear genetic structure. This suggests that the 16 populations of S. procerus exhibit high levels of genetic diversity.

Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Quantitative kinetics reveal that reactions of HO2 are a significant sink for aldehydes in the atmosphere and may initiate the formation of highly oxygenated molecules via autoxidation.

Large aldehydes are widespread in the atmosphere and their oxidation leads to secondary organic aerosols. The current understanding of their chemical transformation processes is limited to hydroxyl radical (OH) oxidation during daytime and nitrate radical (NO3) oxidation during nighttime. Here, we report quantitative kinetics calculations of the reactions of hexanal (C5H11CHO), pentanal (C4H9CHO), and butanal (C3H7CHO) with hydroperoxyl radical (HO2) at atmospheric temperatures and pressures. We find that neither tunneling nor multistructural torsion anharmonicity should be neglected in computing these rate constants; strong anharmonicity at the transition states is also important. We find rate constants for the three reactions in the range 3.2-7.7 × 10-14 cm3 molecule-1 s-1 at 298 K and 1 atm, showing that the HO2 reactions can be competitive with OH and NO3 oxidation under some conditions relevant to the atmosphere. Our findings reveal that HO2-initiated oxidation of large aldehydes may be responsible for the formation of highly oxygenated molecules via autoxidation. We augment the theoretic studies with laboratory flow-tube experiments using an iodide-adduct time-of-flight chemical ionization mass spectrometer to confirm the theoretical predictions of peroxy radicals and the autoxidation pathway. We find that the adduct from HO2 + C5H11CHO undergoes a fast unimolecular 1,7-hydrogen shift with a rate constant of 0.45 s-1. We suggest that the HO2 reactions make significant contributions to the sink of aldehydes.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

The CsmiR1579-CsKr-h1 module mediates rice stem borer development and reproduction: An effective target for transgenic insect-resistant rice.

The rice stem borer (RSB, Chilo suppressalis) is a significant agricultural pest that mainly depends on chemical control. However, it has grown to varied degrees of pesticide resistance, which poses a severe threat to rice production and emphasizes the need for safer, more efficient alternative pest management strategies. Here, in vitro and in vivo experiments analyses reveal miR-1579 binds to the critical transcription factor Krüppel homologue 1 (Kr-h1) and negatively regulates its expression. Overexpression of miR-1579 in larvae with significantly lower levels of Kr-h1 was associated with a decline in larval growth and survival. Furthermore, in female pupae, miR-1579 overexpression led to abnormalities in ovarian development, suggesting that targeting miR-1579 could be a potential management strategy against C. suppressalis. Therefore, we generated transgenic rice expressing miR-1579 and screened three lines that had a single copy of highly abundant mature miR-1579 transcripts. Expectedly, fed with transgenic miR-1579 rice lines were significantly lower survival rates in larvae and high levels of resistance to damage caused by C. suppressalis infestation. These findings suggest that miRNA-mediated RNAi could provide an effective and species-specific strategy for C. suppressalis control.

PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.

Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD.

CK1α deficiency impairs mouse uterine adenogenesis by inducing epithelial cell apoptosis through GSK3ß pathway and inhibiting Foxa2 expression through p53 pathway†.

Uterine glands and their secretions are crucial for conceptus survival and implantation in rodents and humans. In mice, the development of uterine gland known as adenogenesis occurs after birth, whereas the adenogenesis in humans initiates from fetal life and completed at puberty. Uterine adenogenesis involves dynamic epithelial cell proliferation, differentiation, and apoptosis. However, it is largely unexplored about the mechanisms governing adenogenesis. CK1α plays important roles in regulating cell division, differentiation, and death, but it is unknown whether CK1α affects adenogenesis. In the current study, uterus-specific CK1α knockout female mice (Csnk1a1d/d) were infertile resulted from lack of uterine glands. Subsequent analysis revealed that CK1α deletion induced massive apoptosis in uterine epithelium by activating GSK3ß, which was confirmed by injections of GSK3ß inhibitor SB216763 to Csnk1a1d/d females, and the co-treatment of SB216763 and CK1 inhibitor d4476 on cultured epithelial cells. Another important finding was that our results revealed CK1α deficiency activated p53, which then blocked the expression of Foxa2, an important factor for glandular epithelium development and function. This was confirmed by that Foxa2 expression level was elevated in p53 inhibitor pifithrin-α injected Csnk1a1d/d mouse uterus and in vitro dual-luciferase reporter assay between p53 and Foxa2. Collectively, these studies reveal that CK1α is a novel factor regulating uterine adenogenesis by inhibiting epithelial cell apoptosis through GSK3ß pathway and regulating Foxa2 expression through p53 pathway. Uncovering the mechanisms of uterine adenogenesis is expected to improve pregnancy success in humans and other mammals.

Comparative effectiveness of first-line antihypertensive drug classes on the maintenance of estimated glomerular filtration rate (eGFR) in real world primary care.

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients.

Genotyping and traceability analysis of norovirus in Yantai between 2017 and 2019.

To investigate the diversity and evolution of noroviruses in Yantai in recent years, this study focused on the coat protein regions of norovirus-positive samples with nucleic acid detection (cycle threshold) values below 30 between 2017 and 2019. A total of 81 sequences were obtained for genotyping. Initially, a high-throughput sequencing approach was established to perform the whole-genome sequencing of multiple typical diarrheal strains. Using bioinformatics software such as BEAST, recombinant variant analysis was performed for each genotype of the norovirus strains, and genetic evolutionary analysis was conducted for the dominant strain GII.4, as well as the rare variant GII.21. The results showed that there were multiple genotypes such as GI.3, GI.6, GI.7, GII.1, GII.2, GII.3, GII.4, GII.6, GII.13, GII.17, GII.21, and GIX.1 in the positive samples of norovirus from 2017 to 2019. GII.4 is characterized by diverse genotypes, with new changes in antigenic epitopes occurring during the course of the epidemic. This may have led to the emergence of a new pandemic. This suggests a need to strengthen surveillance. The results of this study suggest that attention should be paid to the predominant genotypes prevalent in neighboring countries and regions, and the safety supervision of imported food should be strengthened to aid in the prevention and control of related viruses.

Effect of cornstalk biochar on phytoremediation of Pb-contaminated soil by females and males of Populus deltoides (Salicaceae).

Soil pollution with lead (Pb) has become a serious global concern, adversely affecting the forest ecosystem. This study was conducted to investigate the effects of corn straw on the remediation efficiency of Pb-contaminated soil using Populus deltoides. Female and male P. deltoides cuttings were subjected to soil spiked with 900 mg kg-1 Pb and amended with 5% (v/v) corn straw biochar for 90 days. Under Pb stress, the addition of biochar significantly increased the total biomass accumulation by 29% in females and 26% in males. However, without the addition of biochar, the biomass accumulation was significantly reduced by 11% in females and 3% in males under Pb stress. Females showed a higher uptake and accumulation of Pb in roots and leaves, while males accumulated more Pb in roots and stems and exhibited an increased anti-oxidative capacity. Biochar addition alleviated Pb toxicity in both male and female P. deltoides by immobilizing Pb ion in the soil, reducing Pb uptake and translocation, promoting nutrient uptake, and improving the diversity and stability of the soil bacteria community. Under Pb stress, the relative abundances of metal-resistance bacteria significantly increased, such as the abundance of Bacteroidetes in females and the abundances of Actinobacteria, Firmicutes, and Planctomycetes in males. In brief, the males under biochar addition exhibited promising potential as candidates for phytoremediation of Pb-contaminated soil. This study provides new insights into mechanisms underlying sexually differential responses to Pb stress in the presence of biochar amendment.

Function analysis of CYP321A9 from Spodoptera frugiperda (Lepidoptera: Noctuidae) associated with emamectin benzoate, and a novel insecticide, cyproflanilide detoxification.

The fall armyworm, Spodoptera frugiperda, is an invasive agricultural pest that is a serious threat to agricultural production and global food security. Chemical control is the most effective method for preventing outbreaks of S. frugiperda. However, insecticide resistance often develops as a result of prolonged pesticide use, and the molecular mechanisms involved in insecticide resistance remain unclear. Insect cytochrome P450 monooxygenases play an important role in the detoxification of insecticides and insecticide resistance in Lepidoptera. In our study, the LC50 of a novel insecticide (cyproflanilide) and a conventional insecticide (emamectin benzoate) for S. frugiperda second-instar larvae were 7.04 and 1.61 mg/L, respectively. Furthermore, CYP321A9 expression was upregulated in larvae exposed to these insecticides. Additionally, knockdown of CYP321A9 by feeding larvae with dsRNA for 72 h significantly increased the mortality of S. frugiperda exposed to emamectin benzoate and cyproflanilide by 23.33% and 7.78%, respectively. Our results indicate that CYP321A9 may play an important role in the detoxification of emamectin benzoate and cyproflanilide in S. frugiperda. Our findings provide a basis to better understand the mechanisms of insecticide resistance and contribute to the control of S. frugiperda.

Five New Glycoside Constituents from the Roots of Gentiana crassicaulis Duthie ex Burk.

Three undescribed glycoside constituents, macrophyllosides E-G and a pair of iridoid glycosides genticrasides A/B, together with eleven known glycoside compounds were isolated from the roots of Gentiana crassicaulis Duthie ex Burk. Their structures were identified by means of spectra analysis and data comparison with previous literatures. Interestingly, the glucose moieties in macrophylloside E and F possess free anomeric hydroxy groups. Genticrasides A/B, identified as a pair of iridoid originated lactones, have not been reported from Gentianaceae family up to now. The anti-inflammatory effects of selected compounds were also evaluated through the nitric oxide (NO) production inhibition in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells. In which, macrophyllosides G and D showed NO inhibitory activities with rates of 76.14±4.02 % and 52.44±8.29 % at 100 µg/mL.

Pathogenetic characteristics of infectious diarrhea in Yantai City, Shandong Province, 2018-2019.

Background: Analysis of the pathogenic spectrum, epidemiological characteristics and molecular epidemiological features of important pathogens of infectious diarrhea in Yantai City, Shandong Province, 2018-2019, were analyzed to provide a reference basis for the prevention and control of infectious diarrhea. Methods: A total of 1514 stool specimens were collected within 3 days of the onset of diarrhea in secondary or higher hospitals in Yantai from 2018-2019, and all specimens were tested for the presence of seven major viruses and three major bacteria by employing reverse transcription ploymeraer chain reaction (RT-PCR). Population and seasonal analyses were also performed on positive samples for infectious diarrhea. The top two ranked rotavirus and norovirus were focused on genotyping and analysis of geographical distribution. Results: The study showed that the high prevalence of infectious diarrhea in Yantai, Shandong Province, for two consecutive years in 2018 and 2019 was in young children aged 1-5 years, accounting for 48.6% of the total number of cases. Viral diarrhea was distributed throughout the year with no obvious seasonal distribution, while bacterial diarrhea was predominant in summer. Of 1514 stool specimens, the total positive rate of specimens was 43.92% (665/1514). One pathogen was detected in 507 specimens, two pathogens in 107 specimens, and three pathogens in 44 specimens, with mixed infections accounting for 22.71% of positive specimens (151/665). Viral diarrheal pathogens accounted for 93.23% (620/665) of positive samples. The percentages of positive samples for Rotavirus (RV), Norovirus GI, Norovirus GII, Enterovirus universal (EV), Enteroadenovirus (EAdV), Sapovirus (SaV), Astrovirus (Astv), Salmonella (SE), Listeria monocytogenes (LiMo), and Vibrio parahaemolyticus (VP) were 48.57%, 3.61%, 15.34%, and 10.68% of the total positive samples. Conclusions: This study analyzed in detail the composition of infectious diarrhea pathogen spectrum, pathogen alternation pattern, seasonal distribution and population distribution of pathogens in Yantai City, Shandong Province, 2018-2019, to provide a basis for improving relevant local preventive measures and reducing the disease burden.

Casein kinase 1α is required to maintain murine hypothalamic pro-opiomelanocortin expression.

Hypothalamic pro-opiomelanocortin (POMC) neuron development is considered to play an essential role in the development of obesity. However, the underlying mechanisms remain unclear. Casein kinase 1α (CK1α) was expressed in the embryonic mouse hypothalamus at high levels and colocalized with POMC neurons. CK1α deletion in POMC neurons caused weight gain, metabolic defects, and increased food intake. The number of POMC-expressing cells was considerably decreased in Csnk1a1fl/fl;POMCcre (PKO) mice from embryonic day 15.5 to postnatal day 60, while apoptosis of POMC neurons was not affected. Furthermore, unchanged POMC progenitor cells and a decreased POMC phenotype established CK1α function in hypothalamic POMC neuron development. CK1α deletion led to elevated Notch intracellular domain (NICD) protein expression, and NICD inhibition rescued the PKO mouse phenotype. In summary, CK1α is involved in hypothalamic POMC expression via NICD-POMC signaling, deepening our understanding of POMC neuron development and control of systemic metabolic functions.

Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling.

Casein kinase 1α (CK1α) is present in multiple cellular organelles and plays various roles in regulating neuroendocrine metabolism. Herein, we investigated the underlying function and mechanisms of CK1α-regulated thyrotropin (thyroid-stimulating hormone (TSH)) synthesis in a murine model. Immunohistochemistry and immunofluorescence staining were performed to detect CK1α expression in murine pituitary tissue and its localization to specific cell types. Tshb mRNA expression in anterior pituitary was detected using real-time and radioimmunoassay techniques after CK1α activity was promoted and inhibited in vivo and in vitro. Relationships among TRH/L-T4, CK1α, and TSH were analyzed with TRH and L-T4 treatment, as well as thyroidectomy, in vivo. In mice, CK1α was expressed at higher levels in the pituitary gland tissue than in the thyroid, adrenal gland, or liver. However, inhibiting endogenous CK1α activity in the anterior pituitary and primary pituitary cells significantly increased TSH expression and attenuated the inhibitory effect of L-T4 on TSH. In contrast, CK1α activation weakened TSH stimulation by thyrotropin-releasing hormone (TRH) by suppressing protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling. CK1α, as a negative regulator, mediates TRH and L-T4 upstream signaling by targeting PKC, thus affecting TSH expression and downregulating ERK1/2 phosphorylation and CREB transcriptional activity.

Transcriptomic Analysis Reveals the Detoxification Mechanism of Chilo suppressalis in Response to the Novel Pesticide Cyproflanilide.

Chilo suppressalis is one of the most damaging rice pests in China's rice-growing regions. Chemical pesticides are the primary method for pest control; the excessive use of insecticides has resulted in pesticide resistance. C. suppressalis is highly susceptible to cyproflanilide, a novel pesticide with high efficacy. However, the acute toxicity and detoxification mechanisms remain unclear. We carried out a bioassay experiment with C. suppressalis larvae and found that the LD10, LD30 and LD50 of cyproflanilide for 3rd instar larvae was 1.7 ng/per larvae, 6.62 ng/per larvae and 16.92 ng/per larvae, respectively. Moreover, our field trial results showed that cyproflanilide had a 91.24% control efficiency against C. suppressalis. We investigated the effect of cyproflanilide (LD30) treatment on the transcriptome profiles of C. suppressalis larvae and found that 483 genes were up-regulated and 305 genes were down-regulated in response to cyproflanilide exposure, with significantly higher CYP4G90 and CYP4AU10 expression in the treatment group. The RNA interference knockdown of CYP4G90 and CYP4AU10 increased mortality by 20% and 18%, respectively, compared to the control. Our results indicate that cyproflanilide has effective insecticidal toxicological activity, and that the CYP4G90 and CYP4AU10 genes are involved in detoxification metabolism. These findings provide an insight into the toxicological basis of cyproflanilide and the means to develop efficient resistance management tools for C. suppressalis.