Underlying Mechanisms of the Hedgehog-Like Panicle and Filamentous Leaf Tissue Symptoms Caused by Sclerospora graminicola in Foxtail Millet.

Downy mildew caused by Sclerospora graminicola is a systemic infectious disease affecting foxtail millet production in Africa and Asia. S. graminicola-infected leaves could be decomposed to a state where only the veins remain, resulting in a filamentous leaf tissue symptom. The aim of the present study was to investigate how S. graminicola influences the formation of the filamentous leaf tissue symptoms in hosts at the morphological and molecular levels. We discovered that vegetative hyphae expanded rapidly, with high biomass accumulated at the early stages of S. graminicola infection. In addition, S. graminicola could affect spikelet morphological development at the panicle branch differentiation stage to the pistil and stamen differentiation stage by interfering with hormones and nutrient metabolism in the host, resulting in hedgehog-like panicle symptoms. S. graminicola could acquire high amounts of nutrients from host tissues through secretion of ß-glucosidase, endoglucanase, and pectic enzyme, and destroyed host mesophyll cells by mechanical pressure caused by rapid expansion of hyphae. At the later stages, S. graminicola could rapidly complete sexual reproduction through tryptophan, fatty acid, starch, and sucrose metabolism and subsequently produce numerous oospores. Oospore proliferation and development further damage host leaves via mechanical pressure, resulting in a large number of degraded and extinct mesophyll cells and, subsequently, malformed leaves with only veins left, that is, "filamentous leaf tissue." Our study revealed the S. graminicola expansion characteristics from its asexual to sexual development stages, and the potential mechanisms via which the destructive effects of S. graminicola on hosts occur at different growth stages.

Kosakonia cowanii, a new bacterial pathogen affecting foxtail millet (Setaria italica[L.]P. Beauv.) in China.

Foxtail millet (Setaria italica [L.] P. Beauv.) is an important cereal worldwide. From 2021 to 2022, stalk rot disease of foxtail millet was identified in Shanxi province, northern China, with an 8% and 2% field incidence rate in Xinzhou (2 different locations), respectively. It caused necrosis, decay, stem lodging, and sometimes death. This study aimed to identify the causal agent of the disease through morphophysiological and molecular identification of the isolates. Stalk rot specimens were collected in Xinzhou, from foxtail millet plants exhibiting typical symptoms, and the pathogen was isolated with dilution plating. It was cultured at 28 °C for 48 h on nutrient agar, revealing circular, convex, and pale-yellow colonies, with a smooth surface and an entire edge. Scanning electron microscopy showed that the pathogen is rod shaped, round ended and has an uneven surface ranging from 0.5 to 0.7 µm in diameter and 1.2-2.7 µm in length. It is a motile gram-negative facultative anaerobic bacterium that can reduce nitrate and synthesize catalase but cannot hydrolyze starch. It also shows a negative reaction in the methyl red test and optimum growth at 37 °C. The pathogenicity test was performed on foxtail millet variety 'Jingu 21' stem to confirm Koch's postulates. The biochemical tests were done in the Biolog Gen III MicroPlate, revealing 21 positive chemical sensitivity tests, except those for minocycline and sodium bromate. Furthermore, among 71 carbon sources, the pathogen utilized 50 as the sole carbon source, including sucrose, d-maltose, α-d-lactose, d-galactose, D-sorbitol, D-mannitol, glycerol, and inositol. Finally, molecular characterization of the pathogen using 16S rRNA and rpoB gene sequencing and subsequent phylogenetic analysis identified the strain as Kosakonia cowanii. This study is the first to report K. cowanii as a stalk rot-causing pathogen in foxtail millet.

Genetic Diversity and Pathogenic Variation of the Rice False Smut Pathogen Ustilaginoidea virens from Different Rice Cultivars.

Rice false smut, caused by Ustilaginoidea virens, has become one of the most devastating grain diseases of rice worldwide. Understanding the genetic diversity of U. virens is essential for efficient disease control and breeding for disease resistance. However, little is known about the genetic variation of U. virens from different rice cultivars. We investigated the genetic diversity and pathogenic variation of U. virens isolates from 10 rice cultivars in Zhejiang, China. A total of 260 polymorphic loci and 27 haplotypes were identified based on the 2,137-bp combined DNA fragments of all individuals; hap_4 was the most common haplotype, represented by 41 isolates. Phylogeny indicated that all isolates were divided into four genetic groups. Group I was the largest, with 98 isolates, distributed mainly in eight cultivar populations, whereas 90% of the isolates collected from a Changxiang cultivar were clustered in Group IV. Furthermore, the pairwise FST values exhibited significant genetic differentiation in 27 of the pairwise comparisons between populations, accounting for 23.21% of the total genetic variation. The genetic composition of the isolates of the CX population was distinguishable from that of the other nine populations, and genetic recombination was found in a few isolates. Finally, 27 haplotype representative isolates showed high variation in pathogenicity, and the isolates from the genetic subpopulation I were likely to be more virulent than those from genetic subpopulations II and III. Collectively, these findings suggest that differences in rice cultivars play an important role in the genetic variation of U. virens.

Comparative transcriptome profiling of resistant and susceptible foxtail millet responses to Sclerospora graminicola infection.

BACKGROUND: Downy mildew of foxtail millet, which is caused by the biotrophic oomycete Sclerospora graminicola (Sacc.) Schroeter, is one of the most disruptive diseases. The foxtail millet-S. graminicola interaction is largely unexplored. Transcriptome sequencing technology can help to reveal the interaction mechanism between foxtail millet and its pathogens. RESULTS: Transmission electron microscopy observations of leaves infected with S. graminicola showed that the structures of organelles in the host cells gradually became deformed and damaged, or even disappeared from the 3- to 7-leaf stages. However, organelles in the leaves of resistant variety were rarely damaged. Moreover, the activities of seven cell wall degrading enzymes in resistant and susceptible varieties were also quite different after pathogen induction and most of enzymes activities were significantly higher in the susceptible variety JG21 than in the resistant variety G1 at all stages. Subsequently, we compared the transcriptional profiles between the G1 and JG21 in response to S. graminicola infection at 3-, 5-, and 7-leaf stages using RNA-Seq technology. A total of 473 and 1433 differentially expressed genes (DEGs) were identified in the resistant and susceptible varieties, respectively. The pathway analysis of the DEGs showed that the highly enriched categories were related to glutathione metabolism, plant hormone signalling, phenylalanine metabolism, and cutin, suberin and wax biosynthesis. Some defence-related genes were also revealed in the DEGs, including leucine-rich protein kinase, Ser/Thr protein kinase, peroxidase, cell wall degrading enzymes, laccases and auxin response genes. Our results also confirmed the linkage of transcriptomic data with qRT-PCR data. In particular, LRR protein kinase encoded by Seita.8G131800, Ser/Thr protein kinase encoded by Seita.2G024900 and Seita. 2G024800, which have played an essential resistant role during the infection by S. graminicola. CONCLUSIONS: Transcriptome sequencing revealed that host resistance to S. graminicola was likely due to the activation of defence-related genes, such as leucine-rich protein kinase and Ser/Thr protein kinase. Our study identified pathways and genes that contribute to the understanding of the interaction between foxtail millet and S. graminicola at the transcriptomic level. The results will help us better understand the resistance mechanism of foxtail millet against S. graminicola.

Genome-wide investigation of histone acetyltransferase gene family and its responses to biotic and abiotic stress in foxtail millet (Setaria italica [L.] P. Beauv).

BACKGROUND: Modification of histone acetylation is a ubiquitous and reversible process in eukaryotes and prokaryotes and plays crucial roles in the regulation of gene expression during plant development and stress responses. Histone acetylation is co-regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). HAT plays an essential regulatory role in various growth and development processes by modifying the chromatin structure through interactions with other histone modifications and transcription factors in eukaryotic cells, affecting the transcription of genes. Comprehensive analyses of HAT genes have been performed in Arabidopsis thaliana and Oryza sativa. However, little information is available on the HAT genes in foxtail millet (Setaria italica [L.] P. Beauv). RESULTS: In this study, 24 HAT genes (SiHATs) were identified and divided into four groups with conserved gene structures via motif composition analysis. Phylogenetic analysis of the genes was performed to predict functional similarities between Arabidopsis thaliana, Oryza sativa, and foxtail millet; 19 and 2 orthologous gene pairs were individually identified. Moreover, all identified HAT gene pairs likely underwent purified selection based on their non-synonymous/synonymous nucleotide substitutions. Using published transcriptome data, we found that SiHAT genes were preferentially expressed in some tissues and organs. Stress responses were also examined, and data showed that SiHAT gene transcription was influenced by drought, salt, low nitrogen, and low phosphorus stress, and that the expression of four SiHATs was altered as a result of infection by Sclerospora graminicola. CONCLUSIONS: Results indicated that histone acetylation may play an important role in plant growth and development and stress adaptations. These findings suggest that SiHATs play specific roles in the response to abiotic stress and viral infection. This study lays a foundation for further analysis of the biological functions of SiHATs in foxtail millet.

Simultaneous quantification of hepatitis A virus and norovirus genogroup I and II by triplex droplet digital PCR.

The representative enteric viruses responsible for global foodborne outbreaks that have become an essential concern for health authorities are Norovirus (NoV) and Hepatitis A virus (HAV). Droplet digital PCR (ddPCR) has recently emerged as an alternative platform for virus quantification due to its high precision, ultra-sensitivity, and lack of a standard curve need. Using a ratio-based probe-mixing strategy, we established a triplex ddPCR method to detect norovirus genogroup I (GI), genogroup II (GII), and HAV in food, drinking water, and faecal samples. The probe concentration, annealing temperature, and annealing/extension time were all tuned in the PCR amplification program. The detection limit for NoV GI, NoV GII, and HAV was 7.5, 5.0, and 5.0 copies/reaction, respectively. Furthermore, the suggested approach was validated on 114 samples, demonstrating greater sensitivity, accuracy, and anti-interference performance features than RT-qPCR.

Combining lanthanum-modified bentonite (LMB) and submerged macrophytes alleviates water quality deterioration in the presence of omni-benthivorous fish.

Bioturbation by omni-benthivorous fish often causes sediment resuspension and internal nutrient loading, which boosts phytoplankton growth and may lead to a shift of clear water lakes to a turbid state. Removal of large-sized omni-benthivorous individuals is a lake restoration measure that may revert lakes from a turbid to a clear water state, yet the rapid reproduction of small omni-benthivorous fish in tropical and subtropical shallow lakes may impede such lake recovery. In lake restoration, also a combination of lanthanum-modified bentonite (LMB) and planting submerged macrophytes has been used that may synergistically improve lake water quality. How the combined effect works in the presence of small omni-benthivorous fish has not been studied, which is needed given the high abundances of small omni-benthivorous fish in (sub)tropical lakes. We conducted a two-by-two factorial mesocosm experiment with and without the submerged macrophytes Vallisneria natans and with and without LMB, all in the presence of small crucian carp. At the end of the experiment, turbidity in the V. natans, LMB and combined LMB + V. natans treatments had decreased by 0.8%, 30.3% and 30.9%, respectively, compared with the controls. In addition, the nitrogen (N) and phosphorus (P) release from the sediment in the combined LMB + V. natans treatments had decreased substantially, by 97.4% and 94.3%, respectively, compared with the control. These N and P fluxes were also significantly lower in the combined LMB + V. natans treatments than in the sole LMB treatment (88.1% and 82.3%) or the V. natans treatment (93.2% and 90.3%). Cyanobacteria in the overlying water in the combined LMB + V. natans treatments significantly decreased by 84.1%, 63.5% and 37.0%, respectively, compared with the control and the sole LMB and V. natans treatments. Our results show that LMB and submerged macrophytes complement each other in effectively improving the water quality, even in the presence of small omni-benthivorous fish.

A Review of the Discriminant Analysis Methods for Food Quality Based on Near-Infrared Spectroscopy and Pattern Recognition.

Near-infrared spectroscopy (NIRS) combined with pattern recognition technique has become an important type of non-destructive discriminant method. This review first introduces the basic structure of the qualitative analysis process based on near-infrared spectroscopy. Then, the main pretreatment methods of NIRS data processing are investigated. Principles and recent developments of traditional pattern recognition methods based on NIRS are introduced, including some shallow learning machines and clustering analysis methods. Moreover, the newly developed deep learning methods and their applications of food quality analysis are surveyed, including convolutional neural network (CNN), one-dimensional CNN, and two-dimensional CNN. Finally, several applications of these pattern recognition techniques based on NIRS are compared. The deficiencies of the existing pattern recognition methods and future research directions are also reviewed.

Rapid detection of norovirus genogroup II in clinical and environmental samples using recombinase polymerase amplification.

Norovirus is the leading cause of acute gastroenteritis all over the world, and the most genotype that causes its epidemic is norovirus genogroup II (NoVs GII). Rapid detection of NoVs is important because it can facilitate timely diagnosis. In this study, we designed universal specific primers and an Exo probe to hybridize to all genetic clusters of NoVs GII based on the conserved region at the ORF1-ORF2 junction of the genome. For the first time, we established a rapid and reliable reverse transcription recombinase polymerase amplification (RT-RPA) method for the detection of NoVs GII within 20 min. This method can specifically amplify NoVs GII, and the detection limit was as low as 1.66 × 102 copies/µL. The method was validated in terms of LOD, accuracy, and specificity. We tested 55 real samples including foods, water, and feces. The results showed a sensitivity of 96% and specificity of 100% to NoVs GII. The whole procedure can be operated by a mobile suitcase laboratory, which is useful for resource-limited diagnostic laboratories. This novel real-time RT-RPA assay is an accurate tool for point-of-care testing of NoVs, providing practical support for norovirus-caused disease diagnosis and prevention.

Turning up the heat: warming influences plankton biomass and spring phenology in subtropical waters characterized by extensive fish omnivory.

Understanding how biological communities respond to climate change is a major challenge in ecology. The response of ectotherms to changes in temperature depends not only on their species-specific thermal tolerances but also on temperature-mediated interactions across different trophic levels. Warming is predicted to reinforce trophic cascades in linear aquatic food chains, but little is known about how warming might affect the lower trophic levels of food webs involving extensive fish omnivory, a common scenario in subtropical and tropical waterbodies. In this study, a mesocosm warming experiment was conducted involving a pelagic food chain (fish-zooplankton-phytoplankton) topped by the omnivorous bighead carp [Aristichthys nobilis (Richardson)]. We found that temperature elevation significantly enhanced the growth of fish and suppressed zooplankton, including both metazooplankton and ciliates, while abundances of phytoplankton, despite disruption of temporal dynamics, did not increase correspondingly-likely due to fish predation. Our results suggest that trophic cascades are less unlikely to be reinforced by warming in food chains involving significant omnivory. Moreover, we found that warming advanced the spring abundance peak of phytoplankton abundance and that of the parthenogenetic rotifer Brachionus quadridentatus; whereas, it had no effect on the only sexually reproducing copepod, Mesocyclops leuckarti, presumably due to its prolonged life history. Our study also confirmed that warming may lead to a phenological mismatch between some predators and their prey because of the distinct life histories among taxa, with potentially severe consequences for resource flow in the food chain, at least in the short term.

Transcriptome Profiling Analysis Reveals Co-regulation of Hormone Pathways in Foxtail Millet during Sclerospora graminicola Infection.

Sclerospora graminicola (Sacc.) Schroeter is a biotrophic pathogen of foxtail millet (Setaria italica) and increasingly impacts crop production. We explored the main factors for symptoms such as dwarfing of diseased plants and the "hedgehog panicle" by determining panicle characteristics of varieties infected with S. graminicola and analyzing the endogenous hormone-related genes in leaves of Jingu 21. Results indicated that different varieties infected by S. graminicola exhibited various symptoms. Transcriptome analysis revealed that the ent-copalyl diphosphate synthetase (CPS) encoded by Seita.2G144900 and ent-kaurene synthase (KS) encoded by Seita.2G144400 were up-regulated 4.7-fold and 2.8-fold, respectively. Results showed that the biosynthesis of gibberellin might be increased, but the gibberellin signal transduction pathway might be blocked. The abscisic acid (ABA) 8'-hydroxylase encoded by Seita.6G181300 was continuously up-regulated by 4.2-fold, 2.7-fold, 14.3-fold, and 12.9-fold from TG1 to TG4 stage, respectively. Seita.2G144900 and Seita.2G144400 increased 79-fold and 51-fold, respectively, at the panicle development stage, promoting the formation of a "hedgehog panicle". Jasmonic acid-related synthesis enzymes LOX2s, AOS, and AOC were up-regulated at the early stage of infection, indicating that jasmonic acid played an essential role in early response to S. graminicola infection. The expression of YUC-related genes of the auxin synthesis was lower than that of the control at TG3 and TG4 stages, but the amidase encoded by Seita.2G313400 was up-regulated by more than 30-fold, indicating that the main biosynthesis pathway of auxin had changed. The results suggest that there was co-regulation of the hormone pathways during the infection of foxtail millet by S. graminicola.

Preparation, Bioactivities and Applications in Food Industry of Chitosan-Based Maillard Products: A Review.

Chitosan, a biopolymer possessing numerous interesting bioactivities and excellent technological properties, has received great attention from scientists in different fields including the food industry, pharmacy, medicine, and environmental fields. A series of recent studies have reported exciting results about improvement of the properties of chitosan using the Maillard reaction. However, there is a lack of a systemic review about the preparation, bioactivities and applications in food industry of chitosan-based Maillard reaction products (CMRPs). The presence of free amino groups in chitosan allows it to acquire some stronger or new functional properties via the Maillard reaction. The present review aims to focus on the current research status of synthesis, optimization and structural identification of CMRPs. The applications of CMRPs in the food industry are also discussed according to their biological and technological properties such as antioxidant, antimicrobial activities and inducing conformational changes of allergens in food. Some promising directions for future research are proposed in this review, aiming to provide theoretical guidance for the further development of chitosan and its derivatives.

Changes in the microbial communities in vacuum-packaged smoked bacon during storage.

This study aimed to gain deeper insights into the microbiota composition and population dynamics, monitor the dominant bacterial populations and identify the specific spoilage microorganisms (SSOs) of vacuum-packed bacon during refrigerated storage using both culture-independent and dependent methods. High-throughout sequencing (HTS) showed that the microbial composition changed greatly with the prolongation of storage time. The diversity of microbiota was abundant at the initial stage then experienced a continuous decrease. Lactic acid bacteria (LAB) mainly Leuconostoc and Lactobacillus dominated the microbial population after seven days of storage. A total of 26 isolates were identified from different growth media using traditional cultivation isolation and identification method. Leuconostoc mesenteroides and Leuconostoc carnosum were the most prevalent species since day 15, while Lactobacillus sakei and Lactobacillus curvatus were only found on day 45, suggesting that they could be responsible for the spoilage of bacon. Serratia, Rahnella, Fusobacterium and Lactococcus underwent a dramatic increase at some point in individual batchs which may be considered as potential contributors to the spoilage.

Identification and Characterization of Plant Cell Death-Inducing Secreted Proteins From Ustilaginoidea virens.

Ustilaginoidea virens (Cooke) Takah (telemorph Villosiclava virens) is an ascomycetous fungus that causes rice false smut, one of the most important rice diseases. Fungal effectors often play essential roles in host-pathogen coevolutionary interactions. However, little is known about the functions of U. virens effectors. Here, we performed functional studies on putative effectors in U. virens and demonstrated that 13 of 119 putative effectors caused necrosis or necrosis-like phenotypes in Nicotiana benthamiana. Among them, 11 proteins were confirmed to be secreted, using a yeast secretion system, and the corresponding genes are all highly induced during infection, except UV_44 and UV_4753. Eight secreted proteins were proven to trigger cell death or defenses in rice protoplasts and the secretion signal of these proteins is essential for their cell death-inducing activity. The ability of UV_44 and UV_1423 to trigger cell death is dependent on the predicted serine peptidase and ribonuclease catalytic active sites, respectively. We demonstrated that UV_1423 and UV_6205 are N-glycosylated proteins, which glycosylation has different impacts on their abilities to induce cell death. Collectively, the study identified multiple secreted proteins in U. virens with specific structural motifs that induce cell death or defense machinery in nonhost and host plants.

Differential expression profiling of the early response to Ustilaginoidea virens between false smut resistant and susceptible rice varieties.

BACKGROUND: Rice false smut caused by Ustilaginoidea virens has recently become one of the most devastating rice diseases worldwide. Breeding and deployment of resistant varieties is considered as the most effective strategy to control this disease. However, little is known about the genes and molecular mechanisms underlying rice resistance against U. virens. RESULTS: To explore genetic basis of rice resistance to U. virens, differential expression profiles in resistant 'IR28' and susceptible 'LYP9' cultivars during early stages of U. virens infection were compared using RNA-Seq data. The analyses revealed that 748 genes were up-regulated only in the resistant variety and 438 genes showed opposite expression patterns between the two genotypes. The genes encoding receptor-like kinases and cytoplasmic kinases were highly enriched in this pool of oppositely expressed genes. Many pathogenesis-related (PR) and diterpene phytoalexin biosynthetic genes were specifically induced in the resistant variety. Interestingly, the RY repeat motif was significantly more abundant in the 5'-regulatory regions of these differentially regulated PR genes. Several WRKY transcription factors were also differentially regulated in the two genotypes, which is consistent with our finding that the cis-regulatory W-boxes were abundant in the promoter regions of up-regulated genes in IR28. Furthermore, U. virens genes that are relevant to fungal reproduction and pathogenicity were found to be suppressed in the resistant cultivar. CONCLUSION: Our results indicate that rice resistance to false smut may be attributable to plant perception of pathogen-associated molecular patterns, activation of resistance signaling pathways, induced production of PR proteins and diterpene phytoalexins, and suppression of pathogenicity genes in U. virens as well.

Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: an experimental study.

BACKGROUND AIMS: Tissue-engineered dermis (TED) is thought to be the best treatment for skin defect wounds; however, lack of vascular structures in these products can cause slow vascularization or even transplant failure. We assessed the therapeutic potential of microencapsulated human umbilical cord mesenchymal stromal cells (hUCMSCs) expressing vascular endothelial growth factor (VEGF) in vascularization of TED. METHODS: hUCMSCs were isolated by means of enzymatic digestion and identified by means of testing biological characteristics. hUCMSCs were induced to differentiate into dermal fibroblasts in conditioned induction media. Collagen-chitosan laser drilling acellular dermal matrix (ADM) composite scaffold was prepared by means of the freeze dehydration and dehydrothermal cross-linking method. hUCMSC-derived fibroblasts were implanted on composite scaffolds to construct TED. TED with microencapsulated VEGF gene-modified hUCMSCs was then transplanted into skin defect wounds in pigs. The angiogenesis of TED at 1 week and status of wound healing at 3 weeks were observed. RESULTS: The collagen-chitosan laser ADM composite has a uniform microporous structure. This composite has been used to grow hUCMSC-derived fibroblasts in vitro and to successfully construct stem cell-derived TED. Microencapsulated VEGF gene-modified hUCMSCs were prepared with the use of a sodium alginate-barium chloride one-step encapsulation technology. Seven days after the transplantation of the stem cell-derived TED and microencapsulated VEGF gene-modified hUCMSCs into the skin defect wounds on the backs of miniature pigs, the VEGF expression increased and the TED had a higher degree of vascularization. Re-epithelialization of the wound was completed after 3 weeks. CONCLUSIONS: Microencapsulated VEGF gene-modified hUCMSCs can effectively improve the vascularization of TED and consequently the quality of wound healing.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Chronic diseases and multimorbidity patterns, their recent onset, and risk of new-onset Parkinson's disease and related functional degeneration in older adults: a prospective cohort study.

Background: Certain chronic diseases contribute to increased risks of Parkinson's disease (PD), but the association between time-varying multimorbidity patterns and new-onset PD remains underexplored. Methods: Data were from the Survey of Health, Ageing and Retirement in Europe (SHARE) waves 5-8 conducted between January 2013 and March 2020. Eleven chronic diseases were included, with ≥2 denoting multimorbidity. Three multimorbidity patterns were further defined: somatic multimorbidity (SMM), neuropsychiatric multimorbidity (NPM), and cardiometabolic multimorbidity (CMM). PD-related function degeneration included functional limitations, mobility limitations, depressive symptoms, and cognitive decline. Time-dependent analyses, competing-risk analyses, and mixed-effect models were utilised. Findings: In this prospective cohort study, 557 developed new-onset PD during follow-ups among 64,273 participants included at baseline, as defined by participants' self-reported physician diagnoses. Participants with (vs. without) multimorbidity, SMM, NPM, and CMM were at 1.40-2.70 times higher PD risk after considering the competing role of all-cause death, which remained significant in all sensitivity analyses and were more pronounced in lower-income participants (P for interaction <0.05). Similarly, they tended to develop functional degeneration faster than those without these multimorbidity patterns (P < 0.05). Participants with recent-onset (newly diagnosed in 2015) multimorbidity patterns were at 1.45-3.72 times higher risk of PD than those never diagnosed. Interestingly, they were at comparable or even higher (though P values for >0.05) PD risk compared to participants with multimorbidity patterns diagnosed in 2013 or before. Furthermore, recent-onset (vs. prior diagnosed) NPM exhibited faster functional deterioration and cognitive decline (P for difference <0.05). Interpretation: Our findings suggest that promoting early prevention of multimorbidity, especially recent-onset multimorbidity and NPM, could prevent some subsequent cases of PD and related functional degeneration among older adults. However, further studies are needed to confirm this association. Funding: The National Key Research and Development Program, Ministry of Science and Technology, China; Zhongnanshan Medical Foundation of Guangdong Province; Major Project of the National Social Science Fund of China; Fundamental Research Funds for the Central Universities.

Identifying the potential genes in alpha synuclein driving ferroptosis of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease with aggregation of α-synuclein (α-syn) in substantia nigra (SN). The association between the α-syn and ferroptosis in PD remains unclear. GSE49036 was obtained from the Gene Expression Omnibus (GEO) database and intersected with ferroptosis genes. Bioinformatics analysis was used to identify the potential differentially expressed genes (DEGs) included the development of Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. We screened 8 key genes were modulated and crosslinked by 238 miRNAs. Additionally, 5 hub genes were predicted and 38 lncRNAs targeting 3 key miRNAs were revealed. Finally, 3 hub genes (PIK3CA, BRD4, ATM) and the key lncRNA (NEAT1) were verified in neurotoxic PD models. The in vitro experiments showed that PIK3CA and ATM were significantly upregulated or the BRD4 was downregulated in the rotenone treatment and they could be rescued by the specific ferroptosis inhibitor, liproxstatin-1. The expression of the key lncRNA NEAT1 were consistent with the hub genes in same models. This study identified the proposed NEAT1-PIK3CA/ATM ceRNA network may be a specific biomarker in α-syn driving ferroptosis as well as to predict clinical outcomes and therapeutic targets in PD patients.