Neuroinvasive virus facilitates viral replication by employing lipid droplets to reduce arachidonic acid-induced ferroptosis.

Lipids have been previously implicated in the lifecycle of neuroinvasive viruses. However, the role of lipids in programmed cell death and the relationship between programmed cell death and lipid droplets (LDs) in neuroinvasive virus infection remains unclear. Here, we found that the infection of neuroinvasive virus, such as rabies virus and encephalomyocarditis virus could enhance the LD formation in N2a cells, and decreasing LDs production by targeting diacylglycerol acyltransferase could suppress viral replication. The lipidomics analysis revealed that arachidonic acid (AA) was significantly increased after reducing LD formation by restricting diacylglycerol acyltransferase, and AA was further demonstrated to induce ferroptosis to inhibit neuroinvasive virus replication. Moreover, lipid peroxidation and viral replication inhibition could be significantly alleviated by a ferroptosis inhibitor, ferrostatin-1, indicating that AA affected neuroinvasive virus replication mainly through inducing ferroptosis. Furthermore, AA was demonstrated to activate the acyl-CoA synthetase long-chain family member 4-lysophosphatidylcholine acyltransferase 3-cytochrome P450 oxidoreductase axis to induce ferroptosis. Our findings highlight novel cross-talks among viral infection, LDs, and ferroptosis for the first time, providing a potential target for antiviral drug development.

Characterization of NMCR-3, NMCR-4 and NMCR-5, three novel non-mobile colistin resistance determinants: Implications for MCR-3, MCR-7, and MCR-5 progenitors, respectively.

In this study, the progenitors of MCR-3, MCR-7 and MCR-5, namely NMCR-3, NMCR-4 and NMCR-5, were firstly discovered and indicating Aeromonas was a natural reservoir for MCR-3 and MCR-7. Furthermore, different evolutionary models for MCR-3, MCR-7 and MCR-5 were proposed.

Accuracy of Genomic prediction for fleece traits in Inner Mongolia Cashmere goats.

The fleece traits are important economic traits of goats. With the reduction of sequencing and genotyping cost and the improvement of related technologies, genomic selection for goats has become possible. The research collect pedigree, phenotype and genotype information of 2299 Inner Mongolia Cashmere goats (IMCGs) individuals. We estimate fixed effects, and compare the estimates of variance components, heritability and genomic predictive ability of fleece traits in IMCGs when using the pedigree based Best Linear Unbiased Prediction (ABLUP), Genomic BLUP (GBLUP) or single-step GBLUP (ssGBLUP). The fleece traits considered are cashmere production (CP), cashmere diameter (CD), cashmere length (CL) and fiber length (FL). It was found that year of production, sex, herd and individual ages had highly significant effects on the four fleece traits (P < 0.01). All of these factors should be considered when the genetic parameters of fleece traits in IMCGs are evaluated. The heritabilities of FL, CL, CP and CD with ABLUP, GBLUP and ssGBLUP methods were 0.26 ~ 0.31, 0.05 ~ 0.08, 0.15 ~ 0.20 and 0.22 ~ 0.28, respectively. Therefore, it can be inferred that the genetic progress of CL is relatively slow. The predictive ability of fleece traits in IMCGs with GBLUP (56.18% to 69.06%) and ssGBLUP methods (66.82% to 73.70%) was significantly higher than that of ABLUP (36.73% to 41.25%). For the ssGBLUP method is significantly (29% ~ 33%) higher than that with ABLUP, and which is slightly (4% ~ 14%) higher than that of GBLUP. The ssGBLUP will be as an superiors method for using genomic selection of fleece traits in Inner Mongolia Cashmere goats.

Natural variation in OsSEC13 HOMOLOG 1 modulates redox homeostasis to confer cold tolerance in rice.

Rice (Oryza sativa L.) is a cold-sensitive species that often faces cold stress, which adversely affects yield productivity and quality. However, the genetic basis for low-temperature adaptation in rice remains unclear. Here, we demonstrate that 2 functional polymorphisms in O. sativa SEC13 Homolog 1 (OsSEH1), encoding a WD40-repeat nucleoporin, between the 2 subspecies O. sativa japonica and O. sativa indica rice, may have facilitated cold adaptation in japonica rice. We show that OsSEH1 of the japonica variety expressed in OsSEH1MSD plants (transgenic line overexpressing the OsSEH1 allele from Mangshuidao [MSD], cold-tolerant landrace) has a higher affinity for O. sativa metallothionein 2b (OsMT2b) than that of OsSEH1 of indica. This high affinity of OsSEH1MSD for OsMT2b results in inhibition of OsMT2b degradation, with decreased accumulation of reactive oxygen species and increased cold tolerance. Transcriptome analysis indicates that OsSEH1 positively regulates the expression of the genes encoding dehydration-responsive element-binding transcription factors, i.e. OsDREB1 genes, and induces the expression of multiple cold-regulated genes to enhance cold tolerance. Our findings highlight a breeding resource for improving cold tolerance in rice.

Genetic mapping reveals new loci and alleles for flowering time and plant height using the double round-robin population of barley.

Flowering time and plant height are two critical determinants of yield potential in barley (Hordeum vulgare). Despite their role in plant physiological regulation, a complete overview of the genetic complexity of flowering time and plant height regulation in barley is still lacking. Using a double round-robin population originated from the crossings of 23 diverse parental inbred lines, we aimed to determine the variance components in the regulation of flowering time and plant height in barley as well as to identify new genetic variants by single and multi-population QTL analyses and allele mining. Despite similar genotypic variance, we observed higher environmental variance components for plant height than flowering time. Furthermore, we detected new QTLs for flowering time and plant height. Finally, we identified a new functional allelic variant of the main regulatory gene Ppd-H1. Our results show that the genetic architecture of flowering time and plant height might be more complex than reported earlier and that a number of undetected, small effect, or low-frequency genetic variants underlie the control of these two traits.

Identification and validation of cuproptosis-related genes for diagnosis and therapy in nonalcoholic fatty liver disease.

In recent years, nonalcoholic fatty liver disease (NAFLD) has become a more serious public health issue worldwide. This study strived to investigate the molecular mechanism of pathogenesis of NAFLD and explore promising diagnostic and therapeutic targets for NAFLD. Raw data from GSE130970 were downloaded from the Gene Expression Omnibus database. We used the dataset to analyze the expression levels of cuproptosis-related genes in NAFLD patients and healthy controls to identify the differentially expressed cuproptosis-related genes (DECRGs). The relationship and potential mechanism between DECRGs and clinicopathological factors were examined by enrichment analysis and two consensus clustering methods. We screened key DECRGs based on Random Forest (RF), and then verified the key DECRGs in NAFLD patients, high-fat diet (HFD)-fed mice, and palmitic acid-induced AML12 cells. ROC analysis showed good diagnostic function of DECRGs in normal and NAFLD liver tissue. Two consensus clusters indicated the important role of cuproptosis in the development of NAFLD. We screened for key DECRGs (DLD, DLAT) based on RF and found a close relationship between the DECRGs and clinicopathological factors. We collected clinical blood samples to verify the differences in gene expression levels by qPCR. In addition, we further verified the expression levels of DLD and DLAT in HFD mice and AML12 cells, which showed the same results. This study provides a novel perspective on the pathogenesis of NAFLD. We identified two cuproptosis-related genes that are closely related to NAFLD. These genes may play a significant role in the molecular pathogenesis of NAFLD, which may be useful to make progress in the diagnosis and treatment of NAFLD.

A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.

We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Thermal adaptation of microbial respiration persists throughout long-term soil carbon decomposition.

Soil microbial respiration is expected to show adaptations to changing temperatures, greatly weakening the magnitude of feedback over time, as shown in labile carbon substrates. However, whether such thermal adaptation persists during long-term soil carbon decomposition as carbon substrates decrease in decomposability remains unknown. Here, we conducted a 6-year incubation experiment in natural and arable soils with distinct properties under three temperatures (10, 20 and 30°C). Mass-specific microbial respiration was consistently lower under higher long-term incubation temperatures, suggesting the occurrence and persistence of microbial thermal adaptation in long-term soil carbon decomposition. Furthermore, changes in microbial community composition and function largely explained the persistence of microbial respiratory thermal adaptation. If such thermal adaptation generally occurs in large low-decomposability carbon pools, warming-induced soil carbon losses may be lower than previously predicted and thus may not contribute as much as expected to greenhouse warming.

Convergence of carbon sink magnitude and water table depth in global wetlands.

Wetlands are strategic areas for carbon uptake, but accurate assessments of their sequestration ability are limited by the uncertainty and variability in their carbon balances. Based on 2385 observations of annual net ecosystem production from global wetlands, we show that the mean net carbon sinks of inland wetlands, peatlands and coastal wetlands are 0.57, 0.29 and 1.88 tons of carbon per hectare per year, respectively, with a mean value of 0.57 tons of carbon per hectare per year weighted by the distribution area of different wetland types. Carbon sinks are mainly in Asia and North America. Within and across wetland types, we find that water table depth (WTD) exerts greater control than climate- and ecosystem-related variables, and an increase in WTD results in a stronger carbon sink. Our results highlight an urgent need to sustain wetland hydrology under global change; otherwise, wetlands are at high risk of becoming carbon sources to the atmosphere.

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

PlyKp104, a Novel Phage Lysin for the Treatment of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Other Gram-Negative ESKAPE Pathogens.

Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active lysin, PlyKp104, exhibited >5-log killing against K. pneumoniae, P. aeruginosa, and other Gram-negative representatives of the multidrug-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumonia, Acinetobacter baumannii, P. aeruginosa, and Enterobacter species) without further modification. PlyKp104 displayed rapid killing and high activity over a wide pH range and in high concentrations of salt and urea. Additionally, pulmonary surfactants and low concentrations of human serum did not inhibit PlyKp104 activity in vitro. PlyKp104 also significantly reduced drug-resistant K. pneumoniae >2 logs in a murine skin infection model after one treatment of the wound, suggesting that this lysin could be used as a topical antimicrobial against K. pneumoniae and other MDR Gram-negative infections.

Opposing seasonal temperature dependencies of CO2 and CH4 emissions from wetlands.

Wetlands are critically important to global climate change because of their role in modulating the release of atmospheric greenhouse gases (GHGs) carbon dioxide (CO2 ) and methane (CH4 ). Temperature plays a crucial role in wetland GHG emissions, while the general pattern for seasonal temperature dependencies of wetland CO2 and CH4 emissions is poorly understood. Here we show opposite seasonal temperature dependencies of CO2 and CH4 emissions by using 36,663 daily observations of simultaneous measurements of ecosystem-scale CO2 and CH4 emissions in 42 widely distributed wetlands from the FLUXNET-CH4 database. Specifically, the temperature dependence of CO2 emissions decreased with increasing monthly mean temperature, but the opposite was true for that of CH4 emissions. Neglecting seasonal temperature dependencies may overestimate wetland CO2 and CH4 emissions compared to the use of a year-based static and consistent temperature dependence parameter when only considering temperature effects. Our findings highlight the importance of incorporating the remarkable seasonality in temperature dependence into process-based biogeochemical models to predict feedbacks of wetland GHG emissions to climate warming.

Low soil moisture suppresses the thermal compensatory response of microbial respiration.

The thermal compensatory response of microbial respiration contributes to a decrease in warming-induced enhancement of soil respiration over time, which could weaken the positive feedback between the carbon cycle and climate warming. Climate warming is also predicted to cause a worldwide decrease in soil moisture, which has an effect on the microbial metabolism of soil carbon. However, whether and how changes in moisture affect the thermal compensatory response of microbial respiration are unexplored. Here, using soils from an 8-year warming experiment in an alpine grassland, we assayed the thermal response of microbial respiration rates at different soil moisture levels. The results showed that relatively low soil moisture suppressed the thermal compensatory response of microbial respiration, leading to an enhanced response to warming. A subsequent moisture incubation experiment involving off-plot soils also showed that the response of microbial respiration to 100 d warming shifted from a slight compensatory response to an enhanced response with decreasing incubation moisture. Further analysis revealed that such respiration regulation by moisture was associated with shifts in enzymatic activities and carbon use efficiency. Our findings suggest that future drought induced by climate warming might weaken the thermal compensatory capacity of microbial respiration, with important consequences for carbon-climate feedback.

Microbial communities in terrestrial surface soils are not widely limited by carbon.

Microbial communities in soils are generally considered to be limited by carbon (C), which could be a crucial control for basic soil functions and responses of microbial heterotrophic metabolism to climate change. However, global soil microbial C limitation (MCL) has rarely been estimated and is poorly understood. Here, we predicted MCL, defined as limited availability of substrate C relative to nitrogen and/or phosphorus to meet microbial metabolic requirements, based on the thresholds of extracellular enzyme activity across 847 sites (2476 observations) representing global natural ecosystems. Results showed that only about 22% of global sites in terrestrial surface soils show relative C limitation in microbial community. This finding challenges the conventional hypothesis of ubiquitous C limitation for soil microbial metabolism. The limited geographic extent of C limitation in our study was mainly attributed to plant litter, rather than soil organic matter that has been processed by microbes, serving as the dominant C source for microbial acquisition. We also identified a significant latitudinal pattern of predicted MCL with larger C limitation at mid- to high latitudes, whereas this limitation was generally absent in the tropics. Moreover, MCL significantly constrained the rates of soil heterotrophic respiration, suggesting a potentially larger relative increase in respiration at mid- to high latitudes than low latitudes, if climate change increases primary productivity that alleviates MCL at higher latitudes. Our study provides the first global estimates of MCL, advancing our understanding of terrestrial C cycling and microbial metabolic feedback under global climate change.

cGAS-STING mediates cytoplasmic mitochondrial-DNA-induced inflammatory signal transduction during accelerated senescence of pancreatic ß-cells induced by metabolic stress.

Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by impaired pancreatic ß cell function and insulin resistance. Recent studies have shown that the accumulation of senescent ß cells under metabolic stress conditions leads to the progression of T2DM, while senolysis can improve the prognosis. However, the specific mechanism of ß cell senescence is still unclear. In this study, we found that the increased load of senescence pancreatic ß cells in both older mice and obese mice induced by high-fat diet (HFD) (DIO mice) was accompanied by activation of the Cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway and using cGAS or STING small interfering RNA or STING inhibitor C176 to downregulate this pathway reduced the senescence-associated secretion profile (SASP) and senescence of Min6 cells treated with palmitic acid or hydrogen peroxide. C176 intervention in DIO mice also significantly reduced the inflammation and senescence of the islets, thereby protecting the function of pancreatic ß cell and glucose metabolism. Our study further revealed that mitochondrial DNA (mtDNA) leakage under metabolic stress conditions was critical for the activation of the cGAS-STING pathway, which can be reversed by the mtDNA depleting agent ethidium bromide. Consistently, mtDNA leakage was more severe in older mice and was accelerated by a chronic HFD. In conclusion, we demonstrate that cytoplasmic mtDNA activates the cGAS-STING pathway to mediate SASP during the accelerated senescence of pancreatic ß-cells induced by metabolic stress, and this process can be downregulated by the STING inhibitor C176.

Cadmium-induced pyroptosis is mediated by PERK/TXNIP/NLRP3 signaling in SH-SY5Y cells.

Cadmium (Cd) is a hypertoxic heavy metal that may be exposed to environmental pollutants by humans and animals. It can lead to cognitive disfunction, and is linked to neurodegenerative diseases. Cadmium reportedly can induce endoplasmic reticulum (ER) stress, but few studies have concentrated on it in nerve cells, and the connection between ER stress and neuroinflammation. In this study, in vitro experiments on SH-SY5Y neuroblastoma cells were carried out. We aimed at exploring whether Cd attributed to the cell pyroptosis and the role of PERK in promoting this form of cell damage which can induce strong inflammatory responses. Our results demonstrated that CdCl2 treatment induced excess reactive oxygen species (ROS) production, caused significant modifications in the expression of PERK and increased TXNIP, NLRP3, IL-1ß, IL-18, and caspase1 in SH-SY5Y cells. In addition, scavenging ROS with N-acetylcysteine or inhibiting the expression of PERK by using GSK2606414, rescued the SH-SY5Y cells from cadmium-induced pyroptosis. In conclusion, the results suggest that Cd induces pyroptotic death of SH-SY5Y cells through ER stress, and this may be the potential mechanism of Cd incurring neurological diseases.

Single-cell sequencing reveals the new existence form of dermal papilla cells in the hair follicle regeneration of cashmere goats.

The problem of human hair loss has caused widespread concern, however, such research is difficult because the periodicity is not obvious and the deeper levels knowledge of dermal papilla (DP) stem cells' differentiation are limited. Here, cashmere goats which have obvious periodicity of hair follicles were used, based on unbiased scRNA sequencing, we constructed DP cell lineage differentiation trajectory and revealed the key genes, signals and functions involved in cell fate decisions. And then we revealed the molecular landscape of hair follicle on regeneration. Revealed that DP cells differentiate into four intermediate cell states at different periodicity: Intermediate-cell-10 showed important functions in the growth and maintenance of cashmere; intermediate-cell-1 acting on apoptosis and cashmere shedding; intermediate-cell-0 initiated new follicular cycles, the migration of hair follicles and the occurrence of cashmere; and intermediate-cell-15 are suggested to be DP progenitor cells. In general, we provide new insights for hair regrowth. At the same time, it provides a new research ideas, directions and molecular landscape for the mechanism of dermal papilla cells.

Prevalence and risk factors for subjective cognitive decline and the correlation with objective cognition among community-dwelling older adults in China: Results from the Hubei memory and aging cohort study.

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.

Time-course RNA-seq analysis reveals stage-specific and melatonin-triggered gene expression patterns during the hair follicle growth cycle in Capra hircus.

BACKGROUND: Cashmere goat is famous for its high-quality fibers. The growth of cashmere in secondary hair follicles exhibits a seasonal pattern arising from circannual changes in the natural photoperiod. Although several studies have compared and analyzed the differences in gene expression between different hair follicle growth stages, the selection of samples in these studies relies on research experience or morphological evidence. Distinguishing hair follicle growth cycle according to gene expression patterns may help to explore the regulation mechanisms related to cashmere growth and the effect of melatonin from a molecular level more accurately. RESULTS: In this study, we applied RNA-sequencing to the hair follicles of three normal and three melatonin-treated Inner Mongolian cashmere goats sampled every month during a whole hair follicle growth cycle. A total of 3559 and 988 genes were subjected as seasonal changing genes (SCGs) in the control and treated groups, respectively. The SCGs in the normal group were divided into three clusters, and their specific expression patterns help to group the hair follicle growth cycle into anagen, catagen and telogen stages. Some canonical pathways such as Wnt, TGF-beta and Hippo signaling pathways were detected as promoting the hair follicle growth, while Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Jak-STAT, Fc epsilon RI, NOD-like receptor, Rap1, PI3K-Akt, cAMP, NF-kappa B and many immune-related pathways were detected in the catagen and telogen stages. The PI3K-Akt signaling, ECM-receptor interaction and Focal adhesion were found in the transition stage between telogen to anagen, which may serve as candidate biomarkers for telogen-anagen regeneration. A total of 16 signaling pathways, 145 pathway mRNAs, and 93 lncRNAs were enrolled to construct the pathway-mRNA-lncRNA network, which indicated the function of lncRNAs through interacting with their co-expressed mRNAs. Pairwise comparisons between the control and melatonin-treated groups also indicated 941 monthly differentially expressed genes (monthly DEGs). These monthly DEGs were mainly distributed from April and September, which revealed a potential signal pathway map regulating the anagen stage triggered by melatonin. Enrichment analysis showed that Wnt, Hedgehog, ECM, Chemokines and NF-kappa B signaling pathways may be involved in the regulation of non-quiescence and secondary shedding under the influence of melatonin. CONCLUSIONS: Our study decoded the key regulators of the whole hair follicle growth cycle, laying the foundation for the control of hair follicle growth and improvement of cashmere yield.