The research progress in and perspective of potential fungicides: Succinate dehydrogenase inhibitors.

Succinate dehydrogenase inhibitors (SDHIs) have become one of the fastest growing classes of new fungicides since entering the market, and have attracted increasing attention as a result of their unique structure, high activity and broad fungicidal spectrum. The mechanism of SDHIs is to inhibit the activity of succinate dehydrogenase, thereby affecting mitochondrial respiration and ultimately killing pathogenic fungi. At present, they have become popular varieties researched and developed by major pesticide companies in the world. In the review, we focused on the mechanism, the history, the representative varieties, structure-activity relationship and resistance of SDHIs. Finally, the potential directions for the development of SDHIs were discussed. It is hoped that this review can strengthen the individuals' understanding of SDHIs and provide some inspiration for the development of new fungicides.

Transcriptome analysis of the response provided by Lasiopodomys mandarinus to severe hypoxia includes enhancing DNA repair and damage prevention.

BACKGROUND: Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O2 utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema. To investigate mechanisms underlying the responses of subterranean rodents to severe hypoxia, we performed a cross-species brain transcriptomic analysis using RNA sequencing and identified differentially expressed genes (DEGs) between the subterranean rodent Lasiopodomys mandarinus and its closely related aboveground species L. brandtii under severe hypoxia (5.0% O2, 6 h) and normoxia (20.9% O2, 6 h). RESULTS: We obtained 361 million clean reads, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. We identified 359 and 515 DEGs by comparing the hypoxic and normoxia groups of L. mandarinus and L. brandtii, respectively. Gene Ontology (GO) analysis showed that upregulated DEGs in both species displayed similar terms in response to severe hypoxia; the main difference is that GO terms of L. brandtii were enriched in the immune system. However, in the downregulated DEGs, GO terms of L. mandarinus were enriched in cell proliferation and protein transport and those of L. brandtii were enriched in nuclease and hydrolase activities, particularly in terms of developmental functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs in L. mandarinus were associated with DNA repair and damage prevention as well as angiogenesis and metastasis inhibition, whereas downregulated DEGs were associated with neuronal synaptic transmission and tumor-associated metabolic pathways. In L. brandtii, upregulated KEGG pathways were enriched in the immune, endocrine, and cardiovascular systems and particularly in cancer-related pathways, whereas downregulated DEGs were associated with environmental information processing and misregulation in cancers. CONCLUSIONS: L. mandarinus has evolved hypoxia adaptation by enhancing DNA repair, damage prevention, and augmenting sensing, whereas L. brandtii showed a higher risk of tumorigenesis and promoted innate immunity toward severe hypoxia. These results reveal the hypoxic mechanisms of L. mandarinus to severe hypoxia, which may provide research clues for hypoxic diseases.

Physiological indices and liver gene expression related to glucose supply in Brandt's vole (Lasiopodomys brandtii) exhibit species- and oxygen concentration-specific responses to hypoxia.

Brandt's vole (Lasiopodomys brandtii) is a species with hypoxia tolerance, and glucose serves as the primary energy substrate under hypoxia. However, the glucose supply in Brandt's voles under hypoxia has not been studied. This study aimed to investigate characteristics in physiological indices and liver gene expression associated with glucose supply in Brandt's voles under hypoxia. Serum glucose of Brandt's voles remained stable under 10% O2, increased under 7.5% O2, and decreased under 5% O2. Serum lactate increased under 10% O2, decreased under 7.5% O2, increased at 6 h and decreased at 12 h under 5% O2. Liver glycogen increased under 10% O2, remained constant under 7.5% O2, and reduced under 5% O2. Pepck and G6pase expression associated with gluconeogenesis decreased under 10% O2, while Pepck expression decreased and G6pase expression increased under 7.5% and 5% O2. Regarding genes related to glycogen metabolism, Gys expression decreased at all oxygen concentrations, Phk expression increased under 5% O2, and Gp expression increased under 7.5% and 5% O2. The alterations in glucose, lactate, liver glycogen, and gene expression related to glycogenolysis in Kunming mice (Mus musculus, control species) are similar to discovery of Brandt's voles under 7.5% O2, but gene expression involved in gluconeogenesis and glycogen synthesis increased. The findings suggest that Brandt's voles are more tolerant to hypoxia than Kunming mice, and their physiological indices and liver gene expression related to glucose supply exhibit species- and oxygen concentration-specific responses to hypoxia. This research offers novel insights for studying hypoxia tolerance of Brandt's voles.

The role of lateral hypothalamic nucleus in mediating locomotive behaviors in pigeons (Columba livia).

The lateral hypothalamic nucleus (LHy) is located in the dorsolateral hypothalamus of birds, and it is essential to many life processes. However, limited information is available about the role of LHy in mediating locomotive behaviors. In this work, we investigated the structure and function of LHy in pigeons (Columba livia) by Nissl staining, immunohistochemical (IHC) staining, insituhybridization (ISH) staining and constant current stimulation methods. The results showed that LHy appears crescent in shape, and three-dimensional coordinate value range of LHy is: A: 5.0-8.0 mm, L: 0.7-1.2 mm, D: 9.5-10.3 mm. The dopaminergic neurons in LHy were distributed in small amount and concentrated manner, while the glutamatergic neurons were distributed in a large number and uniform manner. The distribution of the above two neurons at each coronal level showed a significant positive correlation (R2 = 0.7516, P < 0.001). Our work demonstrated that LHy mainly mediates forward movement (P < 0.01) and ipsilateral lateral movement (P < 0.001), and these movements were significantly effected by electrical stimulation intensity. Our results showed that LHy can mediate the generation of directional behavior and this will provide technical support for the study of locomotor behavior regulation in birds.

Multi-stimuli-responsive cyanostilbene derivatives: Their fluorescent and mechanochromic properties, and potential application in water sensing and anti-counterfeiting.

In recent years, aggregation-induced emission luminogens (AIEgens) have witnessed numerous groundbreaking advances in fundamental theoretical research and functional applications. Notably, stimuli-responsive AIEgens have achieved remarkable results, demonstrating immense potential for application in various fields such as chemistry, materials science, biology, and medicine. Herein, two multi-stimuli-responsive cyanostilbene derivatives TPE-CNTPA and PH-CNTPA were synthesized by introducing tetraphenylethylene (TPE) and trifluoromethyl groups, respectively. Primarily, under the combined mechanism of aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT), TPE-CNTPA and PH-CNTPA exhibit "on-off-on" fluorescent emission characteristics in solution. Secondly, under 365 nm ultraviolet light irradiation, the photo-induced isomerization of PH-CNTPA causes changes in photophysical property, demonstrating its responsiveness to ultraviolet light. In addition, TPE-CNTPA and PH-CNTPA exhibit high-contrast mechanochromic properties, providing broader possibilities for their potential applications in various fields. Moreover, owing to the unique fluorescence emission characteristics, TPE-CNTPA and PH-CNTP have enormous potential for application in the field of encryption anti-counterfeiting. Besides, PH-CNTPA can be utilized for the detection of trace water in single or mixed solvents, demonstrating outstanding sensitivity and anti-interference properties in different solvents. This research work reveals the potential in the fields of water sensing and anti-counterfeiting for these two multi-stimuli-responsive compounds.

Spatial and single-nucleus transcriptomics decoding the molecular landscape and cellular organization of avian optic tectum.

The avian optic tectum (OT) has been studied for its diverse functions, yet a comprehensive molecular landscape at the cellular level has been lacking. In this study, we applied spatial transcriptome sequencing and single-nucleus RNA sequencing (snRNA-seq) to explore the cellular organization and molecular characteristics of the avian OT from two species: Columba livia and Taeniopygia guttata. We identified precise layer structures and provided comprehensive layer-specific signatures of avian OT. Furthermore, we elucidated diverse functions in different layers, with the stratum griseum periventriculare (SGP) potentially playing a key role in advanced functions of OT, like fear response and associative learning. We characterized detailed neuronal subtypes and identified a population of FOXG1+ excitatory neurons, resembling those found in the mouse neocortex, potentially involved in neocortex-related functions and expansion of avian OT. These findings could contribute to our understanding of the architecture of OT, shedding light on visual perception and multifunctional association.

Applying molecular docking to pesticides.

Pesticide creation is related to the development of sustainable agricultural and ecological safety, and molecular docking technology can effectively help in pesticide innovation. This paper introduces the basic theory behind molecular docking, pesticide databases, and docking software. It also summarizes the application of molecular docking in the pesticide field, including the virtual screening of lead compounds, detection of pesticides and their metabolites in the environment, reverse screening of pesticide targets, and the study of resistance mechanisms. Finally, problems with the use of molecular docking technology in pesticide creation are discussed, and prospects for the future use of molecular docking technology in new pesticide development are discussed. © 2023 Society of Chemical Industry.

The Heteroepitaxy of Thick ß-Ga2O3 Film on Sapphire Substrate with a ß-(AlxGa1-x)2O3 Intermediate Buffer Layer.

A high aluminum (Al) content ß-(AlxGa1-x)2O3 film was synthesized on c-plane sapphire substrate using the gallium (Ga) diffusion method. The obtained ß-(AlxGa1-x)2O3 film had an average thickness of 750 nm and a surface roughness of 2.10 nm. Secondary ion mass spectrometry results indicated the homogenous distribution of Al components in the film. The Al compositions in the ß-(AlxGa1-x)2O3 film, as estimated by X-ray diffraction, were close to those estimated by X-ray photoelectron spectroscopy, at ~62% and ~61.5%, respectively. The bandgap of the ß-(AlxGa1-x)2O3 film, extracted from the O 1s core-level spectra, was approximately 6.0 ± 0.1 eV. After synthesizing the ß-(AlxGa1-x)2O3 film, a thick ß-Ga2O3 film was further deposited on sapphire substrate using carbothermal reduction and halide vapor phase epitaxy. The ß-Ga2O3 thick film, grown on a sapphire substrate with a ß-(AlxGa1-x)2O3 buffer layer, exhibited improved crystal orientation along the (-201) plane. Moreover, the scanning electron microscopy revealed that the surface quality of the ß-Ga2O3 thick film on sapphire substrate with a ß-(AlxGa1-x)2O3 intermediate buffer layer was significantly improved, with an obvious transition from grain island-like morphology to 2D continuous growth, and a reduction in surface roughness to less than 10 nm.

Study of modeling and optimization for predicting the acute toxicity of carbamate pesticides using the binding information with carrier protein.

To predict drug acute toxicity using the binding information with human serum albumin, our research group established a new method (Carrier protein binding information-toxicity relationship, CPBITR). Unfortunately, the previous model had too few data sets which may affect the accuracy and credibility of the model. In this paper, therefore, we measured the binding modes of three carbamate pesticides, Bendiocarb, Butocarboxim and Dioxacarb with human serum albumin (HSA) to supplement the previously modeled training set. Multispectral methods and molecular docking were used to study their binding modes. We built and optimized the previous models with the combined information of three different toxicity pesticides and HSA in order to find better prediction method. The results showed that Back-propagation Artificial Neural Network model has the best fitting effect among these models. In conclusion, the proposed model effectively improves the accuracy and credibility of the existing model. It results in significant predict drug acute toxicity using the binding information with carrier protein and contribute to drug development and research.

A new method for predicting the acute toxicity of carbamate pesticides based on the perspective of binding information with carrier protein.

Toxicity is one of the most important factors limiting the success of new drug development. In this paper, we built a fast and convenient new method (Carrier protein binding information-toxicity relationship, CPBITR) for predicting drug acute toxicity based on the perspective of binding information with carrier protein. First, we studied the binding information between carbamate pesticides and human serum albumin (HSA) through various spectroscopic methods and molecular docking. Then a total of 16 models were established to clarify the relationship between binding information with HSA and drug toxicity. The results showed that the binding information was related to toxicity. Finally we obtained the effective toxicity prediction model for carbamate pesticides. And the "Platform for Predicting Drug Toxicity Based on the Information of Binding with Carrier Protein" was established with the Back-propagation neural network model. We proposed and proved that it was feasible to predict drug toxicity from this new perspective: binding with carrier protein. According to this new perspective, toxicity prediction model of other drugs can also be established. This new method has the advantages of convenience and fast, and can be used to screen out low-toxic drugs quickly in the early stage. It is helpful for drug research and development.

Synthesis of two new naphthalene-containing compounds and their bindings to human serum albumin.

Two naphthalene-containing compounds, 4-hydroxy-6,7-dimethoxy-1-(4-(trifluoromethyl)phenyl)-2-naphthoic acid (A) and 4-hydroxy-6,7-dimethoxy-1-phenyl-2-naphthoic acid (B), were prepared by several steps. Their bindings to human serum albumin (HSA) were studied by ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, three-dimensional fluorescence, circular dichroism (CD) spectroscopies and molecular docking. The crystal data of these compounds show the structure of the compounds. The results show that the mechanism of the interaction between compound A and HSA is mixed-quenching (both dynamic and static quenching), while that of compound B and HSA is static quenching. The number of binding sites, binding constants and binding distance (r) were obtained. The interaction processes are spontaneous. A mainly interacts with HSA through typical hydrophobic interaction, and B binds to HSA mainly by the hydrogen bonds and van der Waals forces. The conformation of HSA changes slightly after the addition of the compounds. Besides, molecular docking method was used to study the interaction details between the compounds and HSA. This is helpful to understand the absorption and metabolism of these two compounds in the body, and provides a basis for designing naphthalene-containing drugs. Communicated by Ramaswamy H. Sarma.

Relationship between birth head circumference and adulthood quality of life in Chinese people.

AIM: To determine the relationship between birth size and later QOL for Chinese people. METHODS: Birth data of 1074 subjects were obtained from obstetric birth records of Peking Union Medical College Hospital. All subjects are interviewed face to face with the 36-Item Short-Form Health Survey scale by trained investigators. Linear regression model was used to analyse the relationship between QOL and birth head circumference of the subjects after adjusting for the childhood and adulthood characteristics. The relationship was described with regression coefficients (B) and its 95% confidence interval (CI). RESULTS: The mean weighted score of QOL was 88.1 ± 9.1, ranging from 76.8 to 100. Larger birth head circumference meant higher adulthood QOL total score (P= 0.001). After controlling the adulthood confounders, as compared to larger head circumference (≥33 cm), small (<31 cm) and medium head circumferences (31-33 cm) meant lower adulthood QOL scores (B=-2.356, P= 0.005 and B=-1.645, P= 0.014, respectively). The increase of head circumference by 1 cm was associated with 0.480 (95% CI: 0.141, 0.820) increase of QOL score after adjusting adulthood confounders (P= 0.006). CONCLUSIONS: This study validated the relationship between birth head circumference and QOL in later life. Smaller head circumference at birth could predict worse adulthood QOL at above 50 years old.

The reproductive inhibitory effects of levonorgestrel, quinestrol, and EP-1 in Brandt's vole (Lasiopodomys brandtii).

BACKGROUND: Rodent pests can inflict devastating impacts on agriculture and the environment, leading to significant economic damage associated with their high species diversity, reproductive rates and adaptability. Fertility control methods could indirectly control rodent pest populations as well as limit ecological consequences and environmental concerns caused by lethal chemical poisons. Brandt's voles, which are common rodent pests found in the grasslands of middle-eastern Inner Mongolia, eastern regions of Mongolia, and some regions of southern Russia, were assessed in the present study. METHODS: We evaluated the effects of a 2-mg/kg dose of levonorgestrel and quinestrol and a 1:1 mixture of the two (EP-1) on reproductive behavior as well as changes in the reproductive system, reproductive hormone levels, and toxicity in Brandt's voles. RESULTS: Our results revealed that all three fertility control agents can cause reproductive inhibition at a dosage of 2 mg/kg. However, quinestrol caused a greater degree of toxicity, as determined by visible liver damage and reduced expression of the detoxifying molecule CYP1A2. Of the remaining two fertility control agents, EP-1 was superior to levonorgestrel in inhibiting the secretion of follicle-stimulating hormone and causing reproductive inhibition. We believe that these findings could help promote the use of these fertility control agents and, in turn, reduce the use of chemical poisons and limit their detrimental ecological and environmental impacts.

krCRISPR: an easy and efficient strategy for generating conditional knockout of essential genes in cells.

BACKGROUND: CRISPR/Cas9 system is a powerful tool for knocking out genes in cells. However, genes essential for cell survival cannot be directly knocked out. Traditionally, generation of conditional knockout cells requires multiple steps. RESULTS: In this study, we developed an easy and efficient strategy to generate conditional knockout cells by using double episomal vectors - one which expresses gRNA and Cas9 nuclease, and the other expresses an inducible rescue gene. Using this system which we named "krCRISPR" (knockout-rescue CRISPR), we showed that essential genes, HDAC3 and DNMT1, can be efficiently knocked out. When cells reach a desired confluency, the exogenous rescue genes can be silenced by the addition of doxycycline. Furthermore, the krCRISPR system enabled us to study the effects of the essential gene mutations on cells. We showed that the P507L mutation in DNMT1 led to downregulation of global DNA methylation in cells, indicating that it is a disease-causing mutation. CONCLUSIONS: The krCRISPR system offers an easy and efficient platform that facilitates the study of essential genes' function.

[The development of database system of electrocardiographic information].

An ECG information database system was established with 1297 ECG information records and clinical informations. The data and the analysis software in this database can be shared with the international physiological signal databases such as MIT-BIH Arrhythmia. The establishment of this database will facilitate the clinical interpretation, diagnosis and prediction of cardiovascular diseases, especially the cardiac sudden death (SCD).

Birth measurements, family history, and environmental factors associated with later-life hypertensive status.

BACKGROUND: This birth cohort study was conducted to investigate the contribution of prenatal and antenatal environmental exposures to later-life hypertensive status. METHODS: Two thousand five hundred and three individuals born in 1921-1954 at the Peking Union Medical College Hospital (PUMCH) were targeted; 2,081 (83.1%) participated. Clinical examinations included an interview, blood pressure (BP) measurements, and laboratory assays. Statistical analyses were performed using ordinal regression models with later-life hypertensive status as the dependent variable. Similar analyses were for subpopulations divided by family history of hypertension. RESULTS: In the 2,081 subjects, 449 were normotensive, 531 were prehypertensive, and 1,101 had hypertension. Three hundred and forty two hypertensive patients were classified as high-risk (BP ≥180/110 mm Hg, or accompanied with diabetes or three well-established cardiovascular risk factors); the other 759 patients were at mid-to-low risks. Lower birth weight (<2,500 g: odds ratio (OR) = 1.67, P = 0.02; 2,500- <3,000 g: OR = 1.64, P < 0.01; 3,000- <3,500 g, OR = 1.40, P = 0.01), family history of hypertension (OR = 1.73, P < 0.01), poor education (OR = 1.76, P < 0.01), and alcoholism (OR = 3.05, P < 0.01) significantly predicted later-life high-risk hypertension. For participants with hypertensive family history (57.7%), the association with birth weight became nonsignificant, but poor education (OR = 2.33, P < 0.01) and alcoholism (OR = 3.10, P = 0.01) remained important. For participants without hypertensive family history (42.3%), the effects of lower birth weight (<2,500 g: OR = 2.26, P = 0.02; 2,500- <3,000 g: OR = 1.91, P = 0.01; 3,000- <3,500 g, OR = 1.78, P = 0.01) and alcoholism (OR = 3.23, P < 0.01) remained significant. CONCLUSION: Low birth weight, low education, alcoholism, and hypertensive family history are linked to later-life hypertensive status. Low birth weight is also partly associated with one's genetic background; whereas the association with education and alcoholism are independent from hypertensive family history.

Relationship between birth size and coronary heart disease in China.

BACKGROUND: Clinical epidemiological studies suggested a link between fetal growth conditions and later coronary heart disease (CHD) in adult life. However, no such studies have been conducted in a Chinese population. OBJECTIVES: We investigated the association between various birth characteristics and CHD occurrence in a Chinese cohort. DESIGN: Retrospective cohort study. SETTING: Peking Union Medical College Hospital, Beijing, China. PARTICIPANTS: A total of 2,033 subjects who were born at Peking Union Medical College Hospital between 1921 and 1954. MEASUREMENTS: Neonatal birth-weight, placental weight, length from crown to heel, head circumference, and biparietal and occipitofrontal diameters were routinely recorded at the time of birth. All participants were followed up between May 2002 and April 2004 for the occurrence of CHD. RESULTS: CHD was identified in 135 patients. The occurrence of CHD was inversely related to birth sizes, such as birth-weight, head circumference, placental weight (P < 0.05), but was not significantly related to birth length or ponderal index (birth-weight/birth length(3)). After multivariable logistic regression, the ratio of birth-weight to birth length was an independent predictor of CHD along with two other variables: obesity and age. LIMITATIONS: This was a single-center retrospective study. CONCLUSIONS: In China low birth size or birth disproportion, which is suggestive of fetal growth retardation, has an effect on CHD occurrence during adulthood. This suggests that environmental factors operate in both the prenatal and postnatal periods with regard to the development of CHD.

Association of Birth Weight with Health and Long-Term Survival up to Middle and Old Ages in China.

This study is based on an unique dataset of birth records of 11,693 persons born in Beijing, China from 1921-54 and from clinical examinations (May 2003-April 2005) of 2,085 tracked surviving cohort members (aged 50-82) to diagnose seven major chronic diseases. Data were analyzed using the extended Fixed Attribute Dynamics (FAD) method and multivariate regressions. The results of our FAD analysis have shown that, as compared to the persons with low birth weight (<2,500 g), the probability of survival from age 0 to ages 50-56, 63-67 and 68-82 for persons with higher birth weight (2,500-2,999 g, 3,000-3499 g, or ≥3,500 g) was 16-31, 62-104, and 52-108% higher respectively. These estimates display similar patterns for both genders, with somewhat stronger effects in men. Of the 27 estimates of the Odds Ratio of Survival in the FAD analysis, 21 are statistically significant. Controlling for 14 confounding factors, multivariate binary logistic regressions have demonstrated that the risk of having cardiovascular disease and diabetes is negatively associated birth weight; ordinal logit regressions have shown that the number of major chronic diseases at ages 50-82 is significantly associated with birth weight: the lower the birth weight, the higher the risk of having more chronic diseases. We conclude that low birth weight is negatively associated with 1) long-term survival probability from age 0 to ages 50-82, and 2) overall health at middle and old ages. Further research is needed to understand the mechanisms of these effects.

Relationship between perinatal characteristics and later activities of daily living in Chinese elderly people.

BACKGROUND: There are no reports on the association between perinatal characteristics and comprehensive physical function in Chinese elderly people. In this study, we traced 875 subjects who were born at the Peking Union Medical College Hospital (PUMCH) of China from 1921 to 1941. The purpose of this study was to determine the effects of perinatal characteristics on activities of daily living (ADL) function in the geriatric period. METHODS: Birth data of 875 subjects were obtained from obstetric birth records of PUMCH. Adulthood data collection was conducted in the outpatient clinics of PUMCH. During the clinic visits, trained research staff administered physical examinations, activities of daily living scale and a demographic questionnaire. ADLs of all subjects were assessed with the activities of daily living scale. RESULTS: There were 101 subjects whose ADL function was limited and the rate of ADL limitation was 11.5%. Binary logistic regression analyses results showed that the main influencing factors of ADL were age, maternal age at birth, occupation, daily exercise and chronic disease. Subjects whose maternal age at their birth exceeded 35 years were at 2.202 times (1.188 - 4.083) greater risk of ADL limitation when we applied multivariate logistic regression models. CONCLUSIONS: This study validated the relationship between perinatal characteristics and ADL in the geriatric period. An older maternal age at birth could predict a higher ADL limitation rate in the geriatric period.