Northeast China (NEC) is a region sensitive to climate change. However, the adoption of long-season maize cultivars in NEC has caused a substantial yield increase under climate change conditions. It ...is important to determine whether such cultivar adoptions are effective throughout the whole NEC to sustainably increase grain yield. In this study, phenological observations and meteorological data at six sites from 1981 to 2018 were used to detect thermal time (TT) trends during the maize growing period. TT, as a parameter for measuring changes in maize cultivars, was used in the crop simulation model CERES-Maize to examine the variations in maize yield produced with different cultivar × climate combinations in different decades. In NEC, both TTs from emergence to anthesis and from anthesis to physiological maturity showed significant increasing trends from 1981 to 2018. Simulation results for humid areas revealed that adopting longer-season cultivars during 2000–2018 caused yield increases, ranging from 6.3% to 13.3%, compared with the 1980s. However, for stations in semi-humid areas, maize grain yield showed a decrease or a small increase (from −12.7% to 8.0%) when longer-season cultivars were adopted during 2000–2018. For semi-humid areas, decreasing trends in the ratios of rainfed yield to no water-stress yield (Yrainfed/Yno water-stress) and lower Yrainfed/Yno water-stress values during 2000–2018 indicated a growing sensitivity of maize production to water, which was attributed to changes in TT and precipitation. Our results indicate that, for the semi-humid area, maize yield was limited by water after introducing cultivars with higher TT requirement under climate change conditions. Therefore, securing food supplies will depend on increases in water-use efficiency levels and other adaptive strategies, such as varietal diversification, drought-resistant varieties, conservation tillage and irrigation.
A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on ...artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
Circadian clocks are internal molecular time-keeping mechanisms that enable organisms to adjust their physiology and behavior to the daily surroundings. Misalignment of circadian clocks leads to both ...physiological and health impairment. Post-transcriptional regulation and translational regulation of circadian clocks have been extensively investigated. In addition, accumulating evidence has shed new light on the involvement of ribonucleoprotein complexes (RNPs) in the post-transcriptional regulation of circadian clocks. Numerous RNA-binding proteins (RBPs) and RNPs have been implicated in the post-transcriptional modification of circadian clock proteins in different model organisms. Herein, we summarize the advances in the current knowledge on the role of RNP complexes in circadian clock regulation.
The combination of the financial industry and technology is conducive to enhancing its ability to serve the real economy, in which blockchain technology plays an important role. The application of ...blockchain in financial services is mainly reflected in supply chain finance, cross-border payment, credit collection and digital currency. This paper predicts the possible risks and hidden dangers of China’s future blockchain financial industry, analyzes the challenges encountered by the regulator in blockchain management, and proposes the directions the regulator needs to work on in the future.
The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many ...other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes. Using quantitative PCR, negative staining transmission electron microscopy, direct culture, and high-throughput sequencing technologies, we demonstrated the presence of intraocular bacteria. The possibility that the microbiome from these low-biomass communities could be a contamination from other tissues and reagents was carefully evaluated and excluded. We also provide preliminary evidence that a disease-specific microbial signature characterized the intraocular environment of patients with age-related macular degeneration and glaucoma, suggesting that either spontaneous or pathogenic bacterial translocation may be associated with these common sight-threatening conditions. Furthermore, we revealed the presence of an intraocular microbiome in normal eyes from non-human mammals and demonstrated that this varied across species (rat, rabbit, pig, and macaque) and was established after birth. These findings represent the first-ever evidence of intraocular microbiota in humans.
Purpose:
To broaden the mutation and phenotype spectrum of the
GJA8
and
CHMP4B
genes and to reveal genotype-phenotype correlations in a cohort of Chinese patients with congenital cataracts (CCs).
...Methods:
Six Chinese Han families with CCs inherited in an autosomal dominant (AD) pattern were recruited for this study. All patients underwent full ocular examinations. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients and their unaffected family members. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Candidate variants were further confirmed by Sanger sequencing. Bioinformatic analysis with several computational predictive programs was performed to assess the impacts of the candidate variants on the structure and function of the proteins.
Results:
Four heterozygous candidate variants in three different genes (
CRYBB2, GJA8
, and
CHMP4B
) were identified in affected individuals from the six families, including two novel missense variants (
GJA8
: c.64G > C/p. G22R, and
CHMP4B
: c.587C > G/p. S196C), one missense mutation (
CRYBB2
: c.562C > T/p. R188C), and one small deletion (
GJA8
: c.426_440delGCTGGAGGGGACCCT/p.143_147delLEGTL). The three missense mutations were predicted as deleterious in all four computational prediction programs. In the homologous model, the
GJA8
: p.143_147delLEGTL mutation showed a sequence deletion of five amino acids at the cytoplasmic loop of the Cx50 protein, close to the third transmembrane domain. Patients carrying mutations in the same gene showed similar cataract phenotypes at a young age, including total cataracts, Y-sutural with fetal nuclear cataracts, and subcapsular cataracts.
Conclusion:
This study further expands the mutation spectrum and genotype-phenotype correlation of
CRYBB2, GJA8
, and
CHMP4B
underlying CCs. This study sheds light on the importance of comparing congenital cataract phenotypes in patients at the same age stage. It offers clues for the pathogenesis of CCs and allows for an early prenatal diagnosis for families carrying these genetic variants.
Gravity is one of the important environmental factors that influence the physiologies and behaviors of animals and humans, and changes in gravity elicit a variety of physiological and behavioral ...alterations that include impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions. To elucidate the effects of gravity on human physiology and behavior, we examined changes in wrist and trunk activities and heart rate during parabolic flight and the activity of wrist and trunk in water immersion experiments. Data from 195 person-time parabolas performed by eight subjects revealed that the trunk motion counts decreased by approximately half during ascending legs (hypergravity), relative to the data acquired before the parabolic flights. In contrast, the wrist activity remained unchanged. The results from the water immersion experiments demonstrated that in the underwater condition, both the wrist and trunk activities were significantly decreased but the latter decreased to a much lower level. Together, these data suggest that gravitational alterations can result in differential influences on the motions of the wrist and the trunk. These findings might be important for understanding the degeneration of skeleton and muscular system and performance of astronauts in microgravity.
Increasing evidence has pointed to the connection between pre-mRNA splicing and the circadian clock; however, the underlying mechanisms of this connection remain largely elusive. In the filamentous ...fungus
, the core circadian clock elements comprise White Collar 1 (WC-1), WC-2 and FREQUENCY (FRQ), which form a negative feedback loop to control the circadian rhythms of gene expression and physiological processes. Previously, we have shown that in
, the pre-mRNA splicing factors Pre-mRNA-processing ATP-dependent RNA helicase 5 (PRP5), protein arginine methyl transferase 5 (PRMT5) and snRNA gene
are involved in the regulation of splicing of
transcripts, which encode the negative component of the circadian clock system. In this work we further demonstrated that repression of spliceosomal component sRNA genes,
,
, and
, affected the circadian conidiation rhythms. In a
knockdown strain, the molecular rhythmicity was dampened. The expression of a set of snRNP genes including
was up-regulated in a mutant strain lacking the clock component
, suggesting that the function of spliceosome might be under the circadian control. Among these snRNP genes, the levels of
RNA and PRP5 protein oscillated. The distribution of PRP5 in cytosol was rhythmic, suggesting a dynamic assembly of PRP5 in the spliceosome complex in a circadian fashion. Silencing of
caused changes in the transcription and splicing of NCU09649, a clock-controlled gene. Moreover, in the clock mutant
, the rhythmicity of
I-6 splicing was abolished. These data shed new lights on the regulation of circadian clock by the pre-RNA splicing, and PRP5 may link the circadian clock and pre-RNA splicing events through mediating the assembly and function of the spliceosome complex.
The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic ...characterization.
The total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ). The up-regulated proteins between the groups were subjected to biological analysis. Whole exome sequencing (WES) was performed to detect genetic variations.
The most complete human lens proteome to date, which consisted of 1251 proteins, including 55.2% previously unreported proteins, was identified across the experimental groups. Bioinformatics functional annotation revealed the common involvement of cellular metabolic processes, immune responses and protein folding disturbances among the groups. RLSC-over-expressed proteins were characteristically enriched in the intracellular immunological signal transduction pathways. The CC groups featured biological processes relating to gene expression and vascular endothelial growth factor (VEGF) signaling transduction, whereas the molecular functions corresponding to external stress were specific to the ARC groups. Combined with WES, the proteogenomic characterization narrowed the list to 16 candidate causal molecules.
These findings revealed common final pathways with diverse upstream regulation of cataractogenesis in different physiopathological states. This proteogenomic characterization shows translational potential for detecting susceptibility genes/proteins in precision medicine.
Cryptophthalmos is characterized by congenital ocular dysplasia with eyelid malformation. The pathogenicity of mutations in genes encoding components of the FRAS1/FREM protein complex is well ...established, but the underlying pathomechanisms of this disease are still unclear. In the previous study, we generated mice carrying
compound heterozygous mutations using CRISPR/Cas9 and showed that these mice recapitulated the human cryptophthalmos phenotype.
In this study, we tracked changes in the metabolic profile of embryos and expression of metabolism-related genes in
mutant mice on E13.5 compared with wild-type mice. RNA sequencing (RNA-seq) was utilized to decipher the differentiated expression of genes associated with metabolism. Untargeted metabolomics and targeted metabolomics analyses were performed to detect and verify the shifts in the composition of the embryonic metabolome.
Differentially expressed genes participating in amino acid metabolism and energy metabolism were observed by RNA-seq. Transcriptomic analysis suggests that 821 (39.89%) up-regulated genes and 320 (32.99%) down-regulated genes were involved in the metabolic process in the enriched GO terms. A total of 92 significantly different metabolites were identified including creatine, guanosine 5'-monophosphate, cytosine, cytidine 5'-monophosphate, adenine, and L-serine. Interestingly, major shifts related to ATP binding cassette transporters (ABC transporters) and the biosynthesis of amino acids in the composition of the embryonic metabolome were observed by KEGG metabolic analysis, indicating that these pathways could also be involved in the pathogenesis of cryptophthalmos.
We demonstrate that
mutant fetal mice have increased susceptibility to the disruption of eye morphogenesis in association with distinct transcriptomic and metabolomic signatures. Our findings suggest that the metabolomic signature established before birth may play a role in mediating cryptophthalmos in
mutant mice, which may have important implications for the pathogenesis of cryptophthalmos.
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