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Abstract Background The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. Methods A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. Results Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09–5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P

Apodemus peninsulae, a dominant rodent species in temperature forests of northeastern China, is a model animal to explore the ecological functions of reciprocal coevolution of animals and plants. From August to October 2016, 24 infra-red cameras were installed to study the feeding behavior and activity patterns of A. peninsulae in its natural environment. By analyzing 5618 video records, we found that feeding behavior, followed by motor and sentinel behaviors, was their main activity. In the behavior spectra, motor behavior (creep, walk, and skip), feeding behavior (forage, feeding, transport, hoarding, and clean), and sentinel behavior (alert, flee, banishment, and coexistence) accounted for 57.96%, 40.36%, and 1.68% of their behavior, respectively. The peak of feeding behavior occurred between 18:00 and 23:00, and feeding behavior frequency, duration, and activity rhythms differ among August to October. Furthermore, activity was the greatest after sunset and before sunrise, indicating a nocturnal lifestyle; however, from August to October, the start time of the activity was earlier, and the end time was later than usual. On average, mice spent 21.6 ± 11.6 times/night feeding, with a duration of 63.58 ± 98.36 s; while they spent less time in foraging, 39.05 ± 51.63 s. We found a significant difference in feeding and foraging frequency, with mice spending on average 10.84 ± 9.85 times/night and 9.23 ± 11.17 times/night, respectively. Our results show that feeding and foraging behavior is also influenced by light intensity, suggesting a preference for crepuscular periods of the day. Infra-red cameras are very useful in detecting activity patterns of animals that are not easily observable; these cameras are able to capture a large amount of valuable information for research into ecological functions.

Abstract Background Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. Methods In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. Results In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76–5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. Conclusions We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.

Abstract Background We aimed to identify differentially expressed pseudogenes and explore their potential functions in four types of common gynecological malignancies (e.g., cervical squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, and uterine carcinosarcoma) using bioinformatics technology. Materials and methods We identified up-regulated and down-regulated pseudogenes and built a pseudogene-miRNA-mRNA regulatory network through public datasets to explore their potential functions in carcinogenesis and cancer prognosis. Results Among the 63 up-regulated pseudogenes identified, LDHAP5 demonstrated the greatest potential as a candidate pseudogene due to its significant association with poor overall survival in ovarian serous cystadenocarcinoma. KEGG pathway analysis revealed that LDHAP5 showed significant enrichment in MicroRNAs in cancer, Pathway in cancer and PI3K-AKT signaling pathway. Further analysis revealed that EGFR was the potential target mRNA of LDHAP5, which may play an important role in ovarian serous cystadenocarcinoma. Conclusions LDHAP5 was associated with the occurrence and prognosis of ovarian serous cystadenocarcinoma, and thus shows potential as a novel therapeutic target against such cancer.

The diagnosis of biopsy tissue with hematoxylin and eosin (H&E) stained images has been widely used by pathologists to detect the lesions and assess the malignancy. Nevertheless, the diagnostic result relies on the visual observation of pathologists which may vary from person to person under different circumstances. With the advantage of automatically and adaptively learning features at multiple levels of abstraction, Convolutional Neural Networks (CNNs) have rapidly become promising alternatives for pathological image analysis. Therefore, in this paper, we propose an effective method for tumor classification called Hard Example Guided CNN. Our contribution is twofold: firstly, to optimize image representation, we design the CNN architecture as dual-branch, used for extracting global features and local features simultaneously. Secondly, we propose a re-weight training algorithm, which improves learning accuracy and accelerates the convergence by increasing the weight of hard examples. Extensive experiments on multiple datasets demonstrate the superiority of our proposed classification method.

This paper presents the latest progress on pricing and revenue management. Consumer's switching purchase behavior occurs frequently in perishable goods retail market, and we propose a two-period dynamic pricing model among online and offline retailers under heterogeneous purchase behavior of myopic consumers and strategic consumers. Through equilibrium solution and analysis, this study discusses the optimal pricing strategy under the influence of the service perception factor and the proportion of two kinds of consumers. Moreover, this paper analyzes the effect of three pricing strategies on profits to prove the effectiveness of price matching strategy implemented by offline retailers. The results show that the strategic behavior of heterogeneous consumers does not always have a negative impact on the profits of two retailers. The offline retailers can strategically choose to set higher prices to increase profits, and online retailers can also reduce the impact of heterogeneous consumer behavior by disclosing product attribute information. It is unwise for online retailers to take the initiative to match the price set by the offline retailers. In contrast, offline retailers can achieve a win-win situation for both retailers by matching the price of the online retailers actively.

In the process of collaborative innovation of water pollution control industry chain, there are some problems, such as chain break and lack of chain, which lead to poor effect of water pollution collaborative governance and low economic benefits. Therefore, this paper proposes a research method of collaborative innovation mechanism of water pollution treatment industry chain based on complex scientific management. In view of the problems existing in the current industrial chain of water pollution control, the collaborative economic model and matter-element extension model of the industrial chain of water pollution treatment are constructed to improve the synergy effect of each link in the industrial chain and solve the contradictions of each link in the coordination process, so as to provide guarantee for the collaborative innovation of the industrial chain of water pollution control. The experimental results show that the proposed method can bring high economic benefits in the stage of source emission reduction, process interruption, and end treatment, and the water pollution treatment effect is good, which fully verifies the practical application effect of the method. After using the design method to purify, the maximum purification rate reaches more than 80%, and the purification effect reaches class v. The effect is remarkable, which has practical application value.

Salmonella type III secretion system (T3SS) effector SseK3 is a glycosyltransferase delivered directly into the host cells to modify host protein substrates, thus manipulating host cellular signal transduction. Here, we identify and characterize the Arg-GlcNAcylation activity of SseK3 inside bacterial cells. Combining Arg-GlcNAc protein immunoprecipitation and mass spectrometry, we found that 60 bacterial proteins were GlcNAcylated during Salmonella infection, especially the two-component signal transduction system regulatory protein PhoP. Moreover, the Arg-GlcNAcylation of PhoP by SseK3 was detected in vivo and in vitro, and four arginine residues, Arg65, Arg66, Arg118, and Arg215 were identified as the GlcNAcylation sites. Site-directed mutagenesis showed that the PhoP R215A change significantly reduced the DNA-binding ability and arginine to alanine change at all four sites (PhoP 4RA) completely eliminated the DNA-binding ability, suggesting that Arg215 is essential for the DNA-binding activity of PhoP and GlcNAcylation of PhoP affects this activity. Additionally, GlcNAcylation of PhoP negatively regulated the activity of PhoP and decreased the expression of its downstream genes. Overall, our work provides an example of the intra-bacterial activities of the T3SS effectors and increases our understanding of endogenous Arg-GlcNAcylation.

Linderane (LDR), the main active and distinctive component of L. aggregate, is a mechanism-based inactivator of CYP2C9 in vitro, indicating the occurrence of herb-drug interactions. However, little is known about the changes of the pharmacokinetic properties of the common clinical drugs as CYP2C9 substrates after coadministration with LDR. In this study, a selective and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of diclofenac, tolbutamide, and warfarin as CYP2C9 substrates in rat plasma has been developed. Chlorzoxazone was employed as an internal standard (IS), and protein precipitation was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH-C18 (2.1 × 50 mm, 1.7 µm) with 0.1% (v:v) formic acid in water (A) and acetonitrile (B) as the mobile phase with gradient elution. The total run time was only 3.8 min. MS analysis was performed under multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The bioanalytical method was validated, and the selectivity, carryover effects, linearity, precision, accuracy, matrix effect, extraction recovery, and stability were acceptable. The validated method was then successfully applied for evaluating the potential pharmacokinetic interactions when LDR was used along with diclofenac, tolbutamide, and warfarin, respectively. Results showed that the Cmax of diclofenac in the treated group was 1287.82 ± 454.16 μg/L, which was about 5-fold of that in the control group P

Background. Evidence for the association between maternal thyroxine concentration and the risk of fetal congenital heart defects (CHDs) is absent. We aimed to study the association of maternal free and total thyroxine (FT4 and TT4) concentrations and the free-to-total thyroxine proportion (FTT4P, %) with the risk of CHD. Methods. The study was a hospital-based cohort study of 52,047 women who received a universal thyroid function test between 2012 and 2016. CHD was screened by ultrasound between 20 and 24 weeks of gestation or diagnosed until the 42nd day of birth. Adjusted odds ratios (ORs) of fetal CHD were estimated for maternal FT4 and TT4 concentrations or the FTT4P by multivariate logistic regression. Results. A total of 41,647 women with singleton pregnancies were included for the analysis and 215 CHD cases were detected. The FT4 concentration was significantly associated with a higher risk of CHDs (OR, 1.04, 95% confidence interval (CI): 1.01 to 1.07). Each 1% higher FTT4P was related to a 1.41-fold (95% CI: 0.27 to 3.59) higher risk of CHDs. The association became stronger for women with a thyroid function test performed between 12 and 18 weeks of gestation (OR = 1.05 (95% CI: 1.01 to 1.09) for the FT4 concentration and 3.32 (95% CI: 1.43 to 7.73) for the FTT4P). Conclusions. A higher FT4 concentration or FTT4P, measured between 12 and 18 weeks of gestation, was associated with an increased risk of CHDs. These findings may provide new insights into the mechanisms of CHDs and evidence for clinical decisions related to thyroid function tests.

Cinnamomum camphora seed kernel oil (CCSKO) is one of the important natural medium chain triglycerides (MCT) resources, with more than 95.00% of medium chain fatty acids found in the world, and has various physiological effects. However, CCSKO has not been generally recognized as a safe oil or new food resource yet. The acute oral toxicity test and a standard battery of genotoxicity tests (mammalian erythrocyte micronucleus test, Ames test, and in vitro mammalian cell TK gene mutation test) of CCSKO as a new edible plant oil were used in the study. The results of the acute oral toxicity test showed that CCSKO was preliminary non-toxic, with an LD50 value higher than 21.5 g/kg body weight. In the mammalian erythrocyte micronucleus test, there was no concentration-response relationship between the dose of CCSKO and micronucleus value in polychromatic erythrocytes compared to the negative control group. No genotoxicity was observed in the Ames test in the presence or absence of S9 at 5000 μg/mL. In vitro mammalian cell TK gene mutation test showed that CCSKO did not induce in vitro mammalian cell TK gene mutation in the presence or absence of S9 at 5000 μg/mL. These results indicated that CCSKO is a non-toxic natural medium-chain oil.

A few published reports have described anterior spinal artery syndrome (ASAS) with cervical spondylosis based on clinical presentation and/or MRI study, but no photographs of anterior spinal arteries were provided in these studies. Here we present a case of ASAS with cervical spondylosis in a CT angiography (CTA) study. A previously healthy 31‐year‐old man was diagnosed with acute ASAS with cervical spondylosis. Neurological examination revealed four‐limb weakness predominant in the distal part of the upper limbs and superficial sensory impairment below the cervical region. T2‐weighted images on MRI showed an area of hyperintensity in the gray matter of the cervical cord from C3 to C5 with a disc herniation at the C4,5 vertebral level. CTA demonstrated that ASA was occluded at level C4,5, which coincided with the location of disc herniation. Anterior spinal cord decompression and fusions were performed. The patient tolerated the procedure well and had complete resolution of his exertionally dependent myelopathic symptoms 1 week later. In conclusion, although ASAS with cervical spondylosis is rare, it can be diagnosed based on clinical symptoms and MRI and identified by CTA of ASA. A good neurological prognosis is anticipated after anterior spinal cord decompression and fusion is performed if disc herniation is responsible for ASA occlusion.

Ophiocordyceps sinensis (Berk.) is an entomopathogenic fungus that can infect the larva of the ghost moth, Hepialus xiaojinensis, causing mummification after more than one year. This prolonged infection provides a valuable model for studying the immunological interplay between an insect host and a pathogenic fungus. A comparative transcriptome analysis of pre-infection (L) and one-year post-infection (IL) larvae was performed to investigate the immune response in the host. Here, a total of 59,668 unigenes were obtained using Illumina Sequencing in IL and L. Among the 345 identified immune-related genes, 83 out of 86 immune-related differentially expressed genes (DEGs) had a much higher expression in IL than in L. Furthermore, the immune-related DEGs were classified as pathogen recognition receptors (PRRs), signal modulators or transductors, and immune effector molecules. Serpins and protease inhibitors were found to be upregulated in the late phase of infection, suppressing the host’s immune response. Based on the above analysis, the expression levels of most immune-related genes would return to the baseline with the immune response being repressed in the late phase of infection, leading to the fungal immunological tolerance after prolonged infection. Meanwhile, the transcriptomes of IL and the mummified larva (ML) were compared to explore O. sinensis invasion. A total of 1408 novel genes were identified, with 162 of them annotated with putative functions. The gene families likely implicated in O. sinensis pathogenicity have been identified, primarily including serine carboxypeptidase, peroxidase, metalloprotease peptidase, aminopeptidases, cytochrome P450, and oxidoreductase. Furthermore, quantitative real-time PCR (qPCR) was used to assess the expression levels of some critical genes that were involved in immune response and fungal pathogenicity. The results showed that their expression levels were consistent with the transcriptomes. Taken together, our findings offered a comprehensive and precise transcriptome study to understand the immune defense in H. xiaojinensis and O. sinensis invasion, which would accelerate the large-scale artificial cultivation of this medicinal fungus.

Camellia nitidissima is a woody plant with high ornamental value, and its golden-yellow flowers are rich in a variety of bioactive substances, especially flavonoids, that are beneficial to human health. Chalcone isomerases (CHIs) are key enzymes in the flavonoid biosynthesis pathway; however, there is a scarcity of information regarding the CHI family genes of C. nitidissima. In this study, seven CHI genes of C. nitidissima were identified and divided into three subfamilies by phylogenetic analysis. The results of multiple sequence alignment revealed that, unlike CnCHI1/5/6/7, CnCHI2/3/4 are bona fide CHIs that contain all the active site and critical catalytic residues. Analysis of the expression patterns of CnCHIs and the total flavonoid content of the flowers at different developmental stages revealed that CnCHI4 might play an essential role in the flavonoid biosynthesis pathway of C. nitidissima. CnCHI4 overexpression significantly increased flavonoid production in Nicotiana tabacum and C. nitidissima. The results of the dual-luciferase reporter assay and yeast one-hybrid system revealed that CnMYB7 was the key transcription factor that governed the transcription of CnCHI4. The study provides a comprehensive understanding of the CHI family genes of C. nitidissima and performed a preliminary analysis of their functions and regulatory mechanisms.

This retrospective study investigated circulating immune cell alteration in patients with myopic retinopathy. Blood test results and demographic and ocular information of 392 myopic patients and 129 emmetropia controls who attended Changsha Aier Eye Hospital from May 2017 to April 2022 were used in this study. Compared with emmetropia, the percentages of neutrophils and basophils and neutrophil/lymphocyte ratio were significantly higher in myopic patients, whereas the percentages of monocytes and lymphocytes and the counts of lymphocytes and eosinophils were significantly lower in myopic patients. After adjusting for age and hypertension/diabetes, the difference remained. Interestingly, the platelet counts were significantly lower in myopic patients after the adjustments. Further subgroup analysis using multivariable linear regression showed that higher levels of neutrophils, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, lower levels of monocytes, eosinophils, lymphocytes, and platelets, were related to myopic peripheral retinal degeneration (mPRD) and posterior staphyloma (PS). A higher level of basophils was linked to myopic choroidal neovascularization (mCNV). Our results suggest that higher levels of circulating neutrophils and neutrophil/lymphocyte ratio, lower monocytes, eosinophils, lymphocytes, and platelets are related to mild myopic retinopathy. A higher level of circulating basophils is related to the severe form of myopic retinopathy, such as mCNV.

Candidatus Liberibacter asiaticus (CLas) is the causative agent of Huanglongbing (HLB), which has caused great economic losses to the citrus industry. The molecular mechanism of the host response to CLas in wild citrus germplasm has been reported less. Eighteen weeks after inoculation via grafting, all the CLas-inoculated Chongyi wild mandarin (Citrus reticulata) were positive and showed severe anatomical aberrations, suggesting its susceptibility to HLB. Transcriptomics and metabolomics analyses of leaves, barks, and roots from mock-inoculated (control) and CLas-inoculated seedlings were performed. Comparative transcriptomics identified 3,628, 3,770, and 1,716 differentially expressed genes (DEGs) between CLas-infected and healthy tissues in the leaves, barks, and roots, respectively. The CLas-infected tissues had higher transcripts per kilobase per million values and more genes that reached their maximal expression, suggesting that HLB might cause an overall increase in transcript accumulation. However, HLB-triggered transcriptional alteration showed tissue specificity. In the CLas-infected leaves, many DEGs encoding immune receptors were downregulated. In the CLas-infected barks, nearly all the DEGs involved in signaling and plant-pathogen interaction were upregulated. In the CLas-infected roots, DEGs encoding enzymes or transporters involved in carotenoid biosynthesis and nitrogen metabolism were downregulated. Metabolomics identified 71, 62, and 50 differentially accumulated metabolites (DAMs) in the CLas-infected leaves, barks and roots, respectively. By associating DEGs with DAMs, nitrogen metabolism was the only pathway shared by the three infected tissues and was depressed in the CLas-infected roots. In addition, 26 genes were determined as putative markers of CLas infection, and a hypothesized model for the HLB susceptibility mechanism in Chongyi was proposed. Our study may shed light on investigating the molecular mechanism of the host response to CLas infection in wild citrus germplasm.

Distributed task scheduling is an ongoing concern in the field of multi-vehicles, especially in recent years; UAV swarm performing complex tasks endows it with new characteristics, such as self-organization, scalability, reconfigurability, etc. This requires the swarm to have distributed rescheduling capability to dynamically include as many unassigned tasks or new tasks as possible, while satisfying tight time constraints. As one of the most advanced rescheduling methods, the Performance Impact (PI)-MaxAss algorithm provides an important reference for this paper. However, its task exchange-based strategy faces the deadlock problem, and the task rescheduling method should not be limited to this. To this end, a new distributed rescheduling method is proposed for UAV swarms, which combines the local task reordering strategy and the improved task exchange strategy. On the one hand, based on the analysis of the fact that the scheduler is unreasonable for individuals, this paper proposes a local task reordering strategy denoted as PI-Reorder, which simply adds the reordering strategy to the recursive inclusion phase of the PI-MinAvg algorithm, so that unassigned tasks or new tasks can be included without relying on the task exchange. On the other hand, from the phenomenon that two or more vehicles occasionally get caught in an infinite cycle of exchanging the same tasks, the deadlock problem of PI-MaxAss is analyzed, which is then solved by introducing a deadlock-free task exchange strategy, where some defined counters are used to detect and isolate the deadlocks. Then, a rescue scenario is used to demonstrate the performance of the proposed methods, PI-Hybrid compared with PI-MaxAss. Monte Carlo simulation results show that, compared with PI-MaxAss, this method can not only increase the number of allocations to varying degrees, but also reduce the average waiting time, while ensuring deadlock avoidance. The methods can be used not only for the secondary optimization of the existing task exchange scheduling algorithms to escape local optima, but also for task reconfiguration of swarm tasks after adding or removing tasks.

Background Ophiocordyceps sinensis is a species endemic to the alpine and high-altitude areas of the Qinghai-Tibet plateau. Although O. sinensis has been cultivated since the past few years, whether cultivated O. sinensis can completely replace wild O. sinensis remains to be determined. Methods To explore the differences of O. sinensis grown in varied environments, we conducted morphological and transcriptomic comparisons between wild and cultivated samples who with the same genetic background. Results The results of morphological anatomy showed that there were significant differences between wild and cultivated O. sinensis, which were caused by different growth environments. Then, a total of 9,360 transcripts were identified using Illumina paired-end sequencing. Differential expression analysis revealed that 73.89% differentially expressed genes (DEGs) were upregulated in O. sinensis grown under natural conditions compared with that grown under artificial conditions. Functional enrichment analysis showed that some key DEGs related to fatty acid metabolism, including acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-ketoacyl-CoA thiolase, and acetyl-CoA acetyltransferase, were upregulated in wild O. sinensis. Furthermore, gas chromatography-mass spectrometry results confirmed that the fatty acid content of wild O. sinensis was significantly higher than that of cultivated O. sinensis and that unsaturated fatty acids accounted for a larger proportion. Conclusion These results provide a theoretical insight to the molecular regulation mechanism that causes differences between wild and cultivated O. sinensis and improving artificial breeding.

BackgroundThe claudin family is a group of transmembrane proteins related to tight junctions. While their involvement in cancer has been studied extensively, their relationship with the tumor immune microenvironment remains poorly understood. In this research, we focused on genes related to the prognosis of ovarian cancer and explored their relationship with the tumor immune microenvironment.MethodsThe cBioPortal for Cancer Genomics database was used to obtain the genetic variation pattern of the claudin family in ovarian cancer. The ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to explore the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via the Kaplan-Meier plotter. The enrichment of immunological signatures was determined by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor immune microenvironment in ovarian cancer were investigated via the Tumor Immune Estimation Resource (TIMER).ResultsClaudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, CLDN3, CLDN4, CLDN6, CLDN10, CLDN15, and CLDN16 were significantly correlated with overall survival in patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunological signatures of B cell, CD4 T cell, and CD8 T cell. Furthermore, CLDN6 and CLDN10 were negatively correlated and positively correlated, respectively, with immune cell infiltration in ovarian cancer. The expression levels of CLDN6 and CLDN10 were also negatively correlated and positively correlated, respectively, with various gene markers of immune cells in ovarian cancer. Thus, CLDN6 and CLDN10 may participate in immune cell infiltration in ovarian cancer, and these mechanisms may be the reason for poor prognosis.ConclusionOur study showed that CLDN6 and CLDN10 were prognostic biomarkers correlated with the immune microenvironment in ovarian cancer. These results reveal new roles for CLDN6 and CLDN10 as potential therapeutic targets in the treatment of ovarian cancer.

Abstract Background Asian citrus psyllid (ACP) is the primary vector responsible for the transmission of the phloem-limited bacteria Candidatus Liberibacter spp., associated with huanglongbing (HLB), which causes great loss to the citrus industry. Although the roles of leaf color and volatile compounds in the orientation of ACP have been proven, the quantification of color and allelochemicals in the host plant are kept unclear, especially in wild citrus germplasms. Results Chongyi wild mandarin significantly attracted more ACP than wild Hong Kong kumquat, ‘Gannan zao’ navel orange and orange jasmine did in the four-choice and olfactometer assays. The color parameters of the tender leaves from Chongyi wild mandarin and ‘Gannan zao’ were similar. The yellow color in both of them was less saturated than that of the other two plants species, but Chongyi wild mandarin had significant lower carotenoid content (P < 0.05). Notably metabolic profiling differences were observed among the healthy tender shoots from the four tested plants via UPLC-QQQ-MS and GC-MS analyses. Comparing with the other three plant species, 66 and 50 metabolites with significantly different contents in Chongyi wild mandarin were selected as UPLC-identified and GC-identified metabolites of interest (P < 0.05), respectively. Flavonoids accounted for a large group of secondary metabolites of interest, which may function as stimulants or repellents of ACP. Higher content of salicylic acid o-hexoside and lower content of (+)-jasmonic acid in Chongyi wild mandarin may lead to higher amount of methyl salicylate (an ACP attractant) and lower amount of trans-ocimene (an attractant to herbivores’ natural enemies) as well as the suppression of JA-mediated wounding response. This kind of synergistic or antagonistic effect among the metabolites differentially accumulated in Chongyi wild mandarin made it a more attractive host plant to ACP. Conclusions Less saturated yellow color, high amount of attractants, low amount of repellents and insensitivity of JA-mediated wounding response are the four possible reasons why Chongyi wild mandarin attracted more ACP. This work may shed light on the olfactory and visual response of ACP to wild citrus germplasm hosts, and suggest the feasibility of developing ACP attractants or repellents patterned on potential metabolites.

Dielectric-metal nanostructures have lately emerged as one of the most promising approaches to modulating light at the optical frequency. Their remarkable electric and magnetic resonances give them a one-of-a-kind ability to augment local field enhancements with negligible absorption losses. Here, we propose a hybrid metal-dielectric-metal (MDM) nanoantenna that contains a dimer of three-layers of shell nanoparticles. In addition, we only theoretically and numerically show the optical properties of the hybrid dimer nanoantenna. We found that the nanoantenna sustained unidirectional forward scattering with narrow beamwidth (30.9 deg) and strong scattering intensity (up to 5 times larger than the single MDM particle). Furthermore, when the hybrid asymmetric dimer was excited by the plane wave with different electric polarization directions, our findings revealed that the hybrid nanoantenna boosted the gap’s electric near-field while also supporting unidirectional forward scattering. Finally, we analyzed the hybrid dimer with substrates of different materials. It supported strong electric high-order moments along the z-axis and x-axis in gaps between MDM nanoparticles and between MDM nanoparticles and the Ge substrate, owing to the intense displacement currents inside of the dielectric layer. We found that the local electric field of this MDM hybrid dimer nanoantenna with Ge substrate was well improved and attained 3325 v/m.

Mental retardation autosomal dominant 7 (MRD7), or DYRK1A Related Intellectual Disability Syndrome (OMIM 614104) is a developmental syndrome with microcephaly, intellectual disability, language delay and epileptic seizures. Haploinsufficiency of DYRK1A is the cause of MRD7. Here, we generated an induced pluripotent stem cell (iPSC) line with the mutation (DYRK1Ac.1730T>A) from the Peripheral blood mononuclear cell (PBMC) of a MRD7 patient along with an isogenic gene-corrected control iPSC line by CRISPR/Cas9 genome editing. Both iPSC lines showed full pluripotency, normal karyotype and differentiation capacity without integrating vectors. These DYRK1A mutant and isogenic gene-corrected iPSC control line provides a useful model to study the underlying molecular mechanisms of MRD7.

Both gut microbes and environmental contamination may cause metabolic disorders and obesity. However, the relationships among gut microbes, environmental contamination and obesity remain obscure. The drinking water on a national scale (31 cities in China) contained nanocolloid-pattern contamination at the mg/L level, a concentration that is 10- to 100-fold higher than commonly reported pollutants. Exposure to nanocolloids (environmentally related dose, 0.15 mg/kg) for three weeks increased the body weight and leptin levels of mice and decreased the expression of adiponectin. Nanocolloids increased the ratio of Firmicutes to Bacteroidetes, a typical obesity-related phenomenon, in the obese individuals. Oral administration of resveratrol verified the role of gut microbes in the tendency toward obesity induced by nanocolloids. The ratio of Firmicutes to Bacteroidetes is positively correlated with body weight and leptin levels. Compared to the control, the levels of triglycerides and high-density lipoprotein cholesterol were up- and downregulated by the tested nanocolloids at 0.15 mg/kg, respectively. Long-chain fatty acids, lipid metabolites and the expression of lipid synthesis-related genes (Fas, Srebp-1 and ACC-1) were also significantly increased by nanocolloids. The present study provides new insights that improve our understanding the risks of obesity associated with drinking water contamination that are mediated by gut microbes.

Pansy (Viola × wittrockiana Gams.) is an important and attractive ornamental plant with a wide variety of flower colors. To date, the molecular genetic understanding of its colorful petal pigment patterns remains largely unknown. In this study, we analyzed the bicolor petals of “Mengdie” in cytological, physiological, and transcriptomic aspects. Results showed that the difference of flower colors was mainly determined by the pigment distribution in the epidermal cells. Pigment analysis indicated that anthocyanins had strong correlations with color parameters, which acted as the main factor in flower coloration. Comparative transcriptome analysis found a total of 43,908 unigenes with the mean length of 682 bp. There were 24,323, 16,668, 8507, and 7680 unigenes annotated in the Nr, Swiss-Prot, KOG, and KEGG databases, respectively. Differential expression genes (DEGs) showed that the expression of anthocyanin late biosynthesis genes (LBGs), VwF3′H, VwF3′5′H, and VwUFGT, would be likely to play a major role in the color formation of pansy. The expression patterns of selected DEGs were verified by qRT-PCR. This study contributes an excellent insight into molecular mechanism of pigment biosynthesis and provides some useful information for flower color modification in pansy.

Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role in eukaryotic cell death pathways. NleB from enteropathogenic Escherichia coli (EPEC) and SseK1/3 from Salmonella enterica serovar Typhimurium (S. Typhimurium) are T3SS effectors. They are defined as a family of arginine GlcNAc transferase to modify a conserved arginine residue in the death domain (DD) of the death receptor TNFR and their corresponding adaptors to hijack death receptor signaling. Here we identified that these enzymes, NleB, SseK1, and SseK3 could catalyze auto-GlcNAcylation. Residues, including Arg13/53/159/293 in NleB, Arg30/158/339 in SseK1, and Arg153/184/305/335 in SseK3 were identified as the auto-GlcNAcylation sites by mass spectrometry. Mutation of the auto-modification sites of NleB, SseK1, and SseK3 abolished or attenuated the capability of enzyme activity toward their death domain targets during infection. Loss of this ability led to the increased susceptibility of the cells to TNF- or TRAIL-induced cell death during bacterial infection. Overall, our study reveals that the auto-GlcNAcylation of NleB, SseK1, and SseK3 is crucial for their biological activity during infection.

The acidulant is widely used in the production of animal husbandry, and its use is affected by many factors, including environmental factors, dosage, diet composition, and animal’s own factors, so only the correct use of the acidulant can bring good results in animal production and financial income. This article takes acidifier as an example to study the application of compound chemical treatment in livestock farms. In this paper, the effect of using acidulant in the first 1 to 3 weeks after early weaning of piglets is obvious through this experimental study. The effect gradually decreases after 3 weeks and basically has no effect after 4 weeks. Experimental studies have found that the combination of organic acids, antibiotics, and high copper is the most effective. These three have different functions and have complementary or additive effects. Under harsh feeding conditions, especially when the environmental sanitation and environmental conditions are relatively poor, the effect of acidulants is better than good feeding conditions. Experimental data show that fulvic acid depletes milk’s somatic cells in a short period of time and then quickly activates immune function, which is indicated by the increase in lymphocytes in the blood. When a large number of somatic cells migrate to the breast, the somatic cells in milk will also increase, thereby improving the immunity mediated by human cells. The experimental results show that the BFA formula added 1% to the cattle feed. After the research control of this experiment, the milk output increased by 9–17%, and the quality milk output increased by 19.12%, so the use of acidulant increased feed compensation and reduces gastrointestinal diseases and the reproduction of microorganisms in the rumen of dairy cows.

Abstract Background Drugs that inhibit the MEK/ERK pathway have therapeutic benefit in bladder cancer treatment but responses vary with patients, for reasons that are still not very clear. Interferon-α (IFN-α) is also used as a therapeutic agent for bladder cancer treatment but the response rate is low. It was found that IFN-α could enhance the cytotoxic effect of MEK inhibition. However, the potential mechanisms of that are still unclear. Understanding of the cross-talk between the IFN-α and MEK/ERK pathway will help enhance the efficacy of IFN-α or MEK inhibitors on bladder cancer. Methods Immunoprecipitation and pull-down assay were used to reveal the formation of signaling complex. The protein expressions were detected by western blot and immunohistochemistry. The cAMP level, Phosphodiesterase 4D (PDE4D) activity and Prostaglandin E2 (PGE2) concentration in cells, serum and tissues were detected by enzyme-linked immunosorbent assay. The role of PDE4D in bladder tumorigenesis in vivo was examined by the xenograft model. Tissue microarray chips were used to investigate the prognostic roles of PDE4D and tumor progression locus 2 (TPL2) in bladder cancer patients. Results IFN-α down-regulated the cyclooxygenase-2 (COX-2) expression in bladder cancer cells through the inhibition of TPL2/NF-κB pathway; IFN-α also inhibited COX-2 expression by suppressing cAMP signaling through TPL2-ERK mediated PDE4D activity. Reduction of the intracellular cAMP level by PDE4D potentiated the antitumor effect of IFN-α against bladder cancer in vitro and in vivo. Further analysis of clinical samples indicated that low PDE4D expression and high level of TPL2 phosphorylation were correlated to the development and poor prognosis in bladder cancer patients. Conclusions Our data reveal that IFN-α can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN-α in the context of bladder cancer therapy. The antitumor effects of IFN-α and MEK inhibition also depend on the PDE4D-mediated cAMP level in bladder cancer cells. Suppression of the TPL2 phosphorylation and intracellular cAMP level may be possible therapeutic strategies for enhancing the effectiveness of IFN-α and MEK inhibitors in bladder cancer treatment.

Abstract Background Molybdenum (Mo) is an essential micronutrient for almost all biological systems, which holds key positions in several enzymes involved in carbon, nitrogen and sulfur metabolism. In general, this transition metal needs to be coordinated to a unique pterin, thus forming a prosthetic group named molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. The biochemical functions of many molybdoenzymes have been characterized; however, comprehensive analyses of the evolution of Mo metabolism and molybdoproteomes are quite limited. Results In this study, we analyzed almost 5900 sequenced organisms to examine the occurrence of the Mo utilization trait at the levels of Mo transport system, Moco biosynthetic pathway and molybdoproteins in all three domains of life. A global map of Moco biosynthesis and molybdoproteins has been generated, which shows the most detailed understanding of Mo utilization in prokaryotes and eukaryotes so far. Our results revealed that most prokaryotes and all higher eukaryotes utilize Mo whereas many unicellular eukaryotes such as parasites and most yeasts lost the ability to use this metal. By characterizing the molybdoproteomes of all organisms, we found many new molybdoprotein-rich species, especially in bacteria. A variety of new domain fusions were detected for different molybdoprotein families, suggesting the presence of novel proteins that are functionally linked to molybdoproteins or Moco biosynthesis. Moreover, horizontal gene transfer event involving both the Moco biosynthetic pathway and molybdoproteins was identified. Finally, analysis of the relationship between environmental factors and Mo utilization showed new evolutionary trends of the Mo utilization trait. Conclusions Our data provide new insights into the evolutionary history of Mo utilization in nature.

Abstract Background Iron accumulation in basal ganglia accompanies neuronal loss in Huntington’s disease (HD) patients and mouse disease models. Disruption of HD brain iron homeostasis occurs before the onset of clinical signs. Therefore, investigating the mechanism of iron accumulation is essential to understanding its role in disease pathogenesis. Methods N171-82Q HD transgenic mice brain iron was detected by using Diaminobenzidine-enhanced Perls’ stain. Iron homeostatic proteins including iron response protein 1 (IRP1), transferrin (Tf), ferritin and transferrin receptor (TfR) were determined by using western blotting and immunohistochemistry, and their relative expression levels of RNA were measured by RT-PCR in both N171-82Q HD transgenic mice and HEK293 cells expressing N-terminal of huntingtin. Results Iron was increased in striatum and cortex of N171-82Q HD transgenic mice. Analysis of iron homeostatic proteins revealed increased expression of IRP1, Tf, ferritin and TfR in N171-82Q mice striatum and cortex. The same results were obtained in HEK293 cells expressing N-terminal of mutant huntingtin containing 160 CAG repeats. Conclusion We conclude that mutant huntingtin may cause abnormal iron homeostatic pathways by increasing IRP1 expression in Huntington’s disease, suggesting potential therapeutic target.

Abstract Background microRNAs (miRNAs) are important regulators in plant growth and development. miR159 is a conserved miRNA among different plant species and has various functions in plants. Studies on miR159 are mostly done on model plant, Arabidopsis thaliana. In rice, studies on miR159 were either based upon genome-wide expression analyses focused upon responses to different nitrogen forms and abiotic stress or upon phenotypic studies of transgenic plants overexpressing its precursor. STTM (Short Tandem Target Mimic) is an effective tool to block the activity of endogenous mature miRNA activity in plant. Therefore, specific roles of miR159 in rice could be explored by down regulating miR159 through STTM. Results In this study, expression of mature miR159 was successfully suppressed by STTM which resulted in the increased expressions of its two targets genes, OsGAMYB and OsGAMYBL1 (GAMYB-LIKE 1). Overall, STTM159 plants exhibited short stature along with smaller organ size and reduction in stem diameter, length of flag leaf, main panicle, spikelet hulls and grain size. Histological analysis of stem, leaf and mature spikelet hull showed the reduced number of small vascular bundles (SVB), less number of small veins (SV) between two big veins (LV) and less cell number in outer parenchyma. Gene Ontology (GO) enrichment analysis of differentially expressed genes between wild type plants and STTM159 transgenic plants showed that genes involved in cell division, auxin, cytokinin (CK) and brassinosteroids (BRs) biosynthesis and signaling are significantly down-regulated in STTM159 plants. Conclusion Our data suggests that in rice, miR159 positively regulates organ size, including stem, leaf, and grain size due to the promotion of cell division. Further analysis from the RNA-seq data showed that the decreased cell divisions in STTM159 transgenic plants may result, at least partly from the lower expression of the genes involved in cell cycle and hormone homeostasis, which provides new insights of rice miR159-specific functions.

Abstract Background The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Methods Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. Results APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3’UTR. Total 12 SNPs in URR and 24 SNPs in 3’UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3’UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P

Abstract The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. In this study, poly(L-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX), as a model polymer, was chemically conjugated with Gd-DTPA (Gd-diethylenetriaminepentaacetic acid), a T1-contrast agent of MRI, to prepare a Gd-DTPA-conjugated PGG-PTX (PGG-PTX-DTPA-Gd) delivery system used for tumor theranostics. PGG-PTX-DTPA-Gd can be self-assembled to NPs in water with a z-average hydrodynamic diameter about 35.9 nm. The 3 T MRI results confirmed that the relaxivity of PGG-PTX-DTPA-Gd NPs (r1 = 18.98 mM−1S−1) was increased nearly 4.9 times compared with that of free Gd-DTPA (r1 = 3.87 mM−1S−1). The in vivo fluorescence imaging results showed that PGG-PTX-DTPA-Gd NPs could be accumulated in the tumor tissue of NCI-H460 lung cancer animal model by EPR effect, which was similar to PGG-PTX NPs. The MRI results showed that compared with free Gd-DTPA, PGG-PTX-DTPA-Gd NPs showed significantly enhanced and prolonged signal intensity in tumor tissue, which should be attributed to the increased relaxivity and tumor accumulation. PGG-PTX-DTPA-Gd NPs also showed effective antitumor effect in vivo. These results indicated that PGG-PTX-DTPA-Gd NPs are an effective delivery system for tumor theranostics, and should have a potential value in personalized treatment of tumor.

We carried out a pool culture experiment to determine the optimal water treatment depth in loam and clay soils during the late growth stage of super rice. Three controlled water depth treatments of 0–5, 0–10 and 0–15 cm below the soil surface were established using alternate wetting and drying irrigation, and the soil water potential (0 to –25 kPa) was measured at 5, 10 and 15 cm. A 2-cm water layer was used as the control. We measured soil enzyme activities, root antioxidant enzyme activities, chlorophyll fluorescence parameters, and rice yield. The results showed that the 0–5-cm water depth treatment significantly increased root antioxidant enzyme activities in loam soil compared with the control, whereas soil enzyme activities, chlorophyll fluorescence parameters and yield did not differ from those of the control. The 0–10- and 0–15-cm water depth treatments also increased root antioxidant enzyme activities, whereas soil enzyme activities, chlorophyll fluorescence parameters and yield decreased. In clay soil, the soil enzyme activities, root antioxidant enzyme activities, chlorophyll fluorescence parameters, and yield did not change with the 0–5-cm water treatment, whereas the 0–10- and 0–15-cm water treatments improved these parameters. Therefore, the appropriate depths for soil water during the late growth period of rice with a 0 to –25 kPa water potential were 5 cm in loam and 15 cm in clay soil.

Nitrogen is one of the most important nutrient indicators for the growth of crops, and is closely related to the chlorophyll content of leaves and thus influences the photosynthetic ability of the crops. In this study, five hybrid rice varieties were cultivated during one entire growing period in one experimental field supplied with six nitrogen fertilizer levels. Visible and near infrared (vis/NIR) reflectance spectroscopy combined with multivariate analysis was used to identify hybrid rice varieties and nitrogen fertilizer levels, as well as to detect chlorophyll content associated with nitrogen levels. The support vector machine (SVM) algorithm was applied to identify five varieties of hybrid rice and six levels of nitrogen fertilizer. The results demonstrated that different varieties of hybrid rice for each nitrogen level can be well distinguished except for the highest nitrogen level, and no nitrogen level for each rice variety can be completely identified from the other five nitrogen levels. Further, 12 spectral indices combined with partial least square (PLS) analysis were applied for estimating chlorophyll content of rice leaves from plants subjected to different nitrogen levels, and a root mean square error of cross-validation (RMSECV) of 0.506, a coefficient of determination (R2) of 97.8% and a ratio of performance to deviation (RPD) of 4.6 for all rice varieties indicated this as a preferable procedure. This study demonstrates that Vis/NIR spectroscopy can have a great potential for identification of rice varieties and evaluation of nitrogen fertilizer levels.

The urban heat island effect caused by the rapid increase in urban anthropogenic heat has gradually become an important factor affecting the living environment of urban residents. Studying the temporal and spatial variation characteristics of urban anthropogenic heat is of great significance for urban planning and urban ecological service systems. In this study, the urban anthropogenic heat flux (AHF) in 2004, 2009, 2014, and 2020 in the central urban area of Guangzhou was retrieved based on Landsat data and the surface energy balance equation, and the temporal and spatial characteristics of different types of anthropogenic heat were explored by combining the transfer matrix and the migration of the gravity center. The results showed that: (1) The overall change trend of anthropogenic heat in the central urban area of Guangzhou was enhanced, and the degree of enhancement was related to the type of urban functional land. (2) Different types of anthropogenic heat had different characteristics in terms of area expansion and spatial changes. Low-value anthropogenic heat (zero-AHF zone, low-AHF zone, medium-AHF zone) changed drastically in terms of area expansion. High-value anthropogenic heat (medium-AHF zone, high-AHF zone) changed more drastically in space. The increase in urban population, rapid economic development, and increased industrial production activities have stimulated the emission of anthropogenic heat, which has a positive impact on the intensity of anthropogenic heat.

The aberrant activation of a signal transducer and activator of transcription 3 (STAT3) restrains type I interferon (IFN) α/β-induced antiviral responses and is associated with the development of cancer. Designing specific STAT3 inhibitors will thus provide new options for use as IFN therapy. Herein, we identified a novel small molecule, dimethyl 2-(4-(2-(methyl(phenyl(p-tolyl)methyl)amino)ethoxy)benzyl)malonate (CIB-6), which can inhibit the IFN-α-induced interferon stimulated response element (ISRE) luciferase reporter (IC50 value = 6.4 μM) and potentiate the antiproliferative effect of IFN-α in human hepatocellular carcinoma (HCC) cells. CIB-6 was found to bind to the STAT3 Src homology 2 (SH2) domain, thereby selectively inhibiting STAT3 phosphorylation without affecting Janus kinases and STAT1/2. CIB-6 also inhibited the migration and invasion of HCC cells by inhibiting the epithelial–mesenchymal transition (EMT) process. Mechanistically, CIB-6 reduced the expression of β-catenin (an EMT key protein) via upregulating β-transducin repeat-containing protein (β-TrCP) and curbed nuclear factor kappa-B (NF-κB) activation through restricting the phosphorylation of the inhibitor of NF-κB (IκB) kinase (IKK) via STAT3 inhibition. Treatment with CIB-6 significantly retarded tumor growth in nude mice with SK-HEP-1 xenografts. In addition, clinical sample analysis revealed that lower β-TrCP and higher β-catenin expression could affect the median survival time of HCC patients. Our findings suggest that CIB-6 could be a new therapeutic strategy for HCC therapy through STAT3-mediated β-TrCP/β-catenin/NF-κB axis.

The extended range temperature prediction is of great importance for public health, energy and agriculture. The two machine learning methods, namely, the neural networks and natural gradient boosting (NGBoost), are applied to improve the prediction skills of the 2-m maximum air temperature with lead times of 1–35 days over East Asia based on the Environmental Modeling Center, Global Ensemble Forecast System (EMC-GEFS), under the Subseasonal Experiment (SubX) of the National Centers for Environmental Prediction (NCEP). The ensemble model output statistics (EMOS) method is conducted as the benchmark for comparison. The results show that all the post-processing methods can efficiently reduce the prediction biases and uncertainties, especially in the lead week 1–2. The two machine learning methods outperform EMOS by approximately 0.2 in terms of the continuous ranked probability score (CRPS) overall. The neural networks and NGBoost behave as the best models in more than 90% of the study area over the validation period. In our study, CRPS, which is not a common loss function in machine learning, is introduced to make probabilistic forecasting possible for traditional neural networks. Moreover, we extend the NGBoost model to atmospheric sciences of probabilistic temperature forecasting which obtains satisfying performances.

Research on the development of plants grown for energy purposes is important for ensuring the global energy supply and reducing greenhouse gas emissions, and simulation is an important method to study its potential. This paper evaluated the marginal land that could be used to grow sugarcane in the Guangxi Zhuang Autonomous Region. Based on the meteorological data from 2009 to 2017 in this region and field observations from sugarcane plantations, the sensitivity of the APSIM (Agricultural Production Systems sIMulator) model parameters was analyzed by an extended Fourier amplitude sensitivity test, and the APSIM model was validated for sugarcane phenology and yields. During the process of model validation, the value of the determination coefficient R2 of the observed and simulated values was between 0.76 and 0.91, and the consistency index D was between 0.91 and 0.97, indicating a good fit. On this basis, the APSIM sugarcane model was used to simulate the sugarcane production potential of the marginal land on a surface scale, and the distribution pattern of sugarcane production potential in the marginal land was obtained. The simulation results showed that if sugarcane was planted as an energy crop on the marginal land in Guangxi, it would likely yield approximately 42,522.05 × 104 t of cane stalks per year. It was estimated that the sugarcane grown on the marginal land plus 50% of the sugarcane grown on the cropland would be sufficient to produce approximately 3847.37 × 104 t of ethanol fuel. After meeting the demands for vehicle ethanol fuel in Guangxi, 3808.14 × 104 t of ethanol fuel would remain and could be exported to the ASEAN (Association of Southeast Asian Nations).

Rice panicles are composed of many branches with two types of extreme grains, the superior and the inferior. Traditionally, it has been well accepted that earlier flowers result in superior grains and late flowers generate inferior grains. However, these correlations have never been strictly examined in practice. In order to determine the accurate relationship between superior and inferior grains and the flowering order, we localized all the seeds in a panicle in four distinct rice species and systematically documented the rice flowering order, flower locations and the final grain weight for their relationships. Our results demonstrated that the grain weight is more heavily determined by the position of the seeds than by the flowering order. Despite earlier flowering has a positive correlation with the grain weight in general, grains from flowers blooming on the second day after anthesis generally gained the highest weight. This suggests earlier flowers may not result in superior grains. Therefore, we concluded that superior and inferior grains, commonly determined by grain weight, are not fully correlated with the flowering order in rice. Following the order of the grain weight, the superior grains are generally localized at the middle parts of the primary branches, whereas inferior grains were mainly on the last two secondary branches of the lower half part of the panicle. In addition, the weight of inferior grains were affected by spikelet thinning and spraying with exogenous plant growth regulators, indicating that physiological incompetence might be the major reason for the occurrence of the inferior grains.

Phalaenopsis cultivar ‘Panda’ is a beautiful and valuable ornamental for its big flower and unique big spots on the petals and sepals. Although anthocyanins are known as the main pigments responsible for flower colors in Phalaenopsis, and the anthocyanins biosynthetic pathway in Phalaenopsis is generally well known, the detailed knowledge of anthocynins regulation within the spot and non-spot parts in ‘Panda’ flower is limited. In this study, transcriptome and small RNA libraries analysis from spot and non-spot sepal tissues of ‘Panda’ were performed, and we found PeMYB7, PeMYB11, and miR156g, miR858 is associated with the purple spot patterning in its sepals. Transcriptome analyses showed a total 674 differentially expressed genes (DEGs), with 424 downregulated and 250 upregulated (Non-spot-VS-Spot), and 10 candidate DEGs involved in anthocyanin biosynthetic pathway. The qPCR analysis confirmed that seven candidate structure genes (PeANS, PeF3′H, PeC4H, PeF3H, PeF3H1, Pe4CL2, and PeCHI) have significantly higher expressing levels in spot tissues than non-spot tissues. A total 1552 differentially expressed miRNAs (DEMs) were detected with 676 downregulated and 876 upregulated. However, microRNA data showed no DEMs targeting on anthocyanin biosynthesis structure gene, while a total 40 DEMs target transcription factor (TF) genes, which expressed significantly different level in spot via non-spot sepal, including 2 key MYB regulator genes. These results indicated that the lack of anthocyanidins in non-spot sepal may not directly be caused by microRNA suppressing anthocyanidin synthesis genes rather than the MYB genes. Our findings will help in understanding the role of miRNA molecular mechanisms in the spot formation pattern of Phalaenopsis, and would be useful to provide a reference to similar research in other species.

Guided by the target of the Paris Agreement of 2015, it is fundamental to identify regional climate responses to global warming of different magnitudes for Southeast Asia (SEA), a tropical region where human society is particularly vulnerable to climate change. Projected changes in indices characterizing precipitation extremes of the 1.5 °C and 2 °C global warming levels (GWLs) exceeding pre-industrial conditions are analyzed, comparing the reference period (1976–2005) with an ensemble of CORDEX simulations. The results show that projected changes in precipitation extreme indices are significantly amplified over the Indochina Peninsula and the Maritime Continent at both GWLs. The increases of precipitation extremes are essentially affected by enhanced convective precipitation. The number of wet and extremely wet days is increasing more abruptly than both the total and daily average precipitation of all wet days, emphasizing the critical risks linked with extreme precipitation. Additionally, significant changes can also be observed between the GWLs of 1.5 °C and 2 °C, especially over the Maritime Continent, suggesting the high sensitivity of precipitation extremes to the additional 0.5 °C GWL increase. The present study reveals the potential influence of both 1.5 °C and 2 °C GWLs on regional precipitation over SEA, highlights the importance of restricting mean global warming to 1.5 °C above pre-industrial conditions and provides essential information on manageable climate adaptation and mitigation strategies for the developing countries in SEA.

Autophagy is an important intracellular catabolic mechanism involved in the removal of misfolded proteins. Atg14L, the mammalian ortholog of Atg14 in yeast and a critical regulator of autophagy, mediates the production PtdIns3P to initiate the formation of autophagosomes. However, it is not clear how Atg14L is regulated. In this study, we demonstrate that ubiquitination and degradation of Atg14L is controlled by ZBTB16-Cullin3-Roc1 E3 ubiquitin ligase complex. Furthermore, we show that a wide range of G-protein-coupled receptor (GPCR) ligands and agonists regulate the levels of Atg14L through ZBTB16. In addition, we show that the activation of autophagy by pharmacological inhibition of GPCR reduces the accumulation of misfolded proteins and protects against behavior dysfunction in a mouse model of Huntington's disease. Our study demonstrates a common molecular mechanism by which the activation of GPCRs leads to the suppression of autophagy and a pharmacological strategy to activate autophagy in the CNS for the treatment of neurodegenerative diseases.

Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage.