Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis.

BACKGROUND: Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. RESULTS: DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). CONCLUSIONS: Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

Implementing care for women with gestational diabetes after delivery-the challenges ahead.

Gestational diabetes (GDM), defined as glucose intolerance during pregnancy, affects one in six pregnancies globally and significantly increases a woman's lifetime risk of type 2 diabetes mellitus (T2DM). Being a relatively young group, women with GDM are also at higher risk of developing diabetes related complications (e.g., cardiovascular disease, non-alcoholic fatty liver disease) later in life. Children of women with GDM are also likely to develop GDM and this perpetuates a cycle of diabetes, escalating our current pandemic of metabolic disease. The global prevalence of GDM has now risen by more than 30% over the last two decades, making it an emerging public health concern. Antepartum management of maternal glucose is unable to fully mitigate the associated lifetime cardiometabolic risk. Thus, efforts may need to focus on improving care for women with GDM during the postpartum period where prevention or therapeutic strategies could be implemented to attenuate progression of GDM to DM and its associated vascular complications. However, strategies to provide care for women in the postpartum period often showed disappointing results. This has led to a missed opportunity to halt the progression of impaired glucose tolerance/impaired fasting glucose to DM in women with GDM. In this review, we examined the challenges in the management of women with GDM after delivery and considered how each of these challenges are defined and could present as a gap in translating evidence to clinical care. We highlighted challenges related to postpartum surveillance, postpartum glucose testing strategies, postpartum risk factor modification, and problems encountered in engagement of patients/providers to implement interventions strategies in women with GDM after delivery. We reasoned that a multisystem approach is needed to address these challenges and to retard progression to DM and cardiovascular disease (CVD) in women with GDM pregnancies. This is very much needed to pave way for an improved, precise, culturally sensitive and wholistic care for women with GDM.

Protocol for three-dimensional shaping strategy via solidifying polygonal nanofluid drops.

Mesoscale to nanoscale three-dimensional (3D) fabrication mostly requires complicated industry processing techniques. Here, we present a protocol for 3D shaping control by solidifying a water-based TiO2 nanofluid drop on a polygonal wettability-patterned surface. We detail the steps for preparing stable TiO2 nanofluid and wettability-patterned surfaces. We then describe the experimental procedure to obtain various and precise 3D morphologies by adjusting the deposited TiO2 nanofluid drop volume. This protocol provides a promising technique for future 3D manufacturing. For complete details on the use and execution of this protocol, please refer to Jiang et al.1.

Real-Space Imaging of Intrinsic Symmetry-Breaking Spin Textures in a Kagome Lattice.

The electronic orders in kagome materials have emerged as a fertile platform for studying exotic quantum states, and their intertwining with the unique kagome lattice geometry remains elusive. While various unconventional charge orders with broken symmetry is observed, the influence of kagome symmetry on magnetic order has so far not been directly observed. Here, using a high-resolution magnetic force microscopy, it is, for the first time, observed a new lattice form of noncollinear spin textures in the kagome ferromagnet in zero magnetic field. Under the influence of the sixfold rotational symmetry of the kagome lattice, the spin textures are hexagonal in shape and can further form a honeycomb lattice structure. Subsequent thermal cycling measurements reveal that these spin textures transform into a non-uniform in-plane ferromagnetic ground state at low temperatures and can fully rebuild at elevated temperatures, showing a strong second-order phase transition feature. Moreover, some out-of-plane magnetic moments persist at low temperatures, supporting the Kane-Mele scenario in explaining the emergence of the Dirac gap. The observations establish that the electronic properties, including both charge and spin orders, are strongly coupled with the kagome lattices.

Efficient vegetation indices for phenotyping of abiotic stress tolerance in tea plant (Camellia sinensis (L.) Kuntze).

Early non-destructive detection of stress effect is crucial for efficient breeding strategies and germplasm characterization. Recently developed hyperspectral technologies allow to perform fast real-time phenotyping through reflectance-based vegetation indices. However, efficiency of these vegetation indices has to be validated for each crop in different environment. The aim of this study was to reveal efficient vegetation indices for phenotyping of abiotic stress (cold, freezing and nitrogen deficiency) response in tea plant. Among 31 studied VIs, few indices were efficient to distinguish tolerant and susceptible tea plants under abiotic stress: ZMI (Zarco-Tejada & Miller Index), VREI1,2,3 (Vogelmann Red Edge Indices), RENDVI (Red Edge Normalized Difference Vegetation Index), CTR1 and CTR2 (Carter Indices). Most of these indices are calculated based on reflectance in near-infrared area at 705-760 nm, indicating this range as promising for tea germplasm characterization under abiotic stresses. Tolerant tea plants showed the following values under freezing: ZMI ≥1.90, VREI1 ≥ 1.40, RENDVI ≥0.38, Ctr1 ≤ 1.74. The leaf N-content was positively correlated (Pearson's) with the following indices ZMI, VREI1, RENDVI, while negatively correlated with CTR, and VREI2,3. These results will be useful for tea germplasm management, genomics and breeding research aimed at abiotic stress tolerance of tea plant.

Naringenin inhibits the microsomal triglyceridetransfer protein/apolipoprotein B axis to inhibit intestinal metaplasia progression.

Intestinal metaplasia (IM) is a premalignant condition that increases the risk for subsequent gastric cancer (GC). Traditional Chinese medicine generally plays a role in the treatment of IM, and the phytochemical naringenin used in Chinese herbal medicine has shown therapeutic potential for the treatment of gastric diseases. However, naringenin's specific effect on IM is not yet clearly understood. Therefore, this study identified potential gene targets for the treatment of IM through bioinformatics analysis and experiment validation. Two genes (MTTP and APOB) were selected as potential targets after a comparison of RNA-seq results of clinical samples, the GEO dataset (GSE78523), and naringenin-related genes from the GeneCards database. The results of both cell and animal experiments suggested that naringenin can improve the changes in the intestinal epithelial metaplasia model via MTTP/APOB expression. In summary, naringenin likely inhibits the MTTP/APOB axis and therefore inhibits IM progression. These results support the development of naringenin as an anti-IM agent and may contribute to the discovery of novel IM therapeutic targets.

Genomic variation of 363 diverse tea accessions unveils the genetic diversity, domestication, and structural variations associated with tea adaptation.

Domestication has shaped the population structure and agronomic traits of tea plants, yet the complexity of tea population structure and genetic variation that determines these traits remains unclear. We here investigated the resequencing data of 363 diverse tea accessions collected extensively from almost all tea distributions and found that the population structure of tea plants was divided into eight subgroups, which were basically consistent with their geographical distributions. The genetic diversity of tea plants in China decreased from southwest to east as latitude increased. Results also indicated that Camellia sinensis var. assamica (CSA) illustrated divergent selection signatures with Camellia sinensis var. sinensis (CSS). The domesticated genes of CSA were mainly involved in leaf development, flavonoid and alkaloid biosynthesis, while the domesticated genes in CSS mainly participated in amino acid metabolism, aroma compounds biosynthesis, and cold stress. Comparative population genomics further identified ~730 Mb novel sequences, generating 6,058 full-length protein-encoding genes, significantly expanding the gene pool of tea plants. We also discovered 217,376 large-scale structural variations and 56,583 presence and absence variations (PAVs) across diverse tea accessions, some of which were associated with tea quality and stress resistance. Functional experiments demonstrated that two PAV genes (CSS0049975 and CSS0006599) were likely to drive trait diversification in cold tolerance between CSA and CSS tea plants. The overall findings not only revealed the genetic diversity and domestication of tea plants, but also underscored the vital role of structural variations in the diversification of tea plant traits.

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research.

BACKGROUND: Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research. METHODS: In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing. RESULTS: The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages. CONCLUSIONS: The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

Reducing transient severe motion artifacts of gadoxetate disodium-enhanced MRI by oxygen inhalation: effective for pleural effusion but not ascites.

OBJECTIVES: To evaluate the efficacy of low-flow oxygen inhalation in mitigating transient severe motion (TSM) artifacts associated with gadoxetate disodium-enhanced hepatic magnetic resonance imaging (MRI). METHODS: Patients undergoing gadoxetate disodium-enhanced MRI were included. During the examination, the experimental group received oxygen at 2 L/min via nasal cannula, while the control group did not. Images and TSM scores were evaluated and compared across precontrast, arterial, venous, and hepatobiliary phases. Subgroup analyses were conducted based on the presence of pleural effusion or ascites. RESULTS: A total of 325 patients were included. The motion scores were highest in the arterial phase and lowest in the hepatobiliary phase in both groups, but were significantly lower in the experimental group (p < 0.05). The incidence of TSM was significantly lower in the experimental group (3.29%) compared to the control group (13.29%, p = 0.01). While pleural effusion was associated with reduced image quality in both groups (p < 0.05), the image quality in the pleural effusion category was higher in the experimental group than in the control group. Oxygen inhalation showed limited efficacy in mitigating TSM related to ascites. CONCLUSIONS: Low-flow oxygen inhalation can effectively reduce the occurrence of gadoxetate disodium-related TSM. Pleural effusion may impair respiratory function and contribute to TSM, which can be alleviated by oxygen supplementation. However, Oxygen inhalation is less effective under the condition of ascites.

Relevance of genetic causes and environmental adaptation of Cronobacter spp. isolated from infant and follow-up formula production factories and retailed products in China: A 7-year period of continuous surveillance based on genome-wide analysis.

The possible contamination routes, environmental adaptation, and genetic basis of Cronobacter spp. in infant and follow-up formula production factories and retailed products in mainland China have been determined by laboratory studies and whole-genome comparative analysis in a 7-year nationwide continuous surveillance spanning from 2012 to 2018. The 2-year continuous multicenter surveillance of the production process (conducted in 2013 and 2014) revealed that the source of Cronobacter spp. in the dry-blending process was the raw dry ingredients and manufacturing environment (particularly in the vibro sieve and vacuum cleaner), while in the combined process, the main contamination source was identified as the packing room. It is important to note that, according to the contamination control knowledge obtained from the production process surveillance, the contamination rate of retail powdered infant formula (PIF) and follow-up formula (FUF) products in China decreased significantly from 2016 onward, after improving the hygiene management practices in factories. The prevalence of Cronobacter spp. in retailed PIF and FUF in China in 2018 was dramatically reduced from 1.55 % (61/3925, in 2012) to an average as low as 0.17 % (13/7655 in 2018). Phenotype determination and genomic analysis were performed on a total of 90 Cronobacter spp. isolates obtained from the surveillance. Of the 90 isolates, only two showed resistance to either cefazolin or cefoxitin. The multilocus sequence typing results revealed that C. sakazakii sequence type 1 (ST1), ST37, and C. malonaticus ST7 were the dominant sequence types (STs) collected from the production factories, while C. sakazakii ST1, ST4, ST64, and ST8 were the main STs detected in the retailed PIF and FUF nationwide. One C. sakazakii ST4 isolate (1.1 %, 1/90) had strong biofilm-forming ability and 13 isolates (14.4 %, 13/90) had weak biofilm-forming ability. Genomic analysis revealed that Cronobacter spp. have a relatively stable core-genome and an increasing pan-genome size. Plasmid IncFIB (pCTU3) was prevalent in this genus and some contained 14 antibacterial biocide- and metal-resistance genes (BMRGs) including copper, silver, and arsenic resistant genes. Plasmid IncN_1 was predicted to contain 6 ARGs. This is the first time that a multi-drug resistance IncN_1 type plasmid has been reported in Cronobacter spp. Genomic variations with respect to BMRGs, virulence genes, antimicrobial resistance genes (ARGs), and genes involved in biofilm formation were observed among strains of this genus. There were apparent differences in copies of bcsG and flgJ between the biofilm-forming group and non-biofilm-forming group, indicating that these two genes play key roles in biofilm formation. The findings of this study have improved our understanding of the contamination characteristics and genetic basis of Cronobacter spp. in PIF and FUF and their production environment in China and provide important guidance to reduce contamination with this pathogen during the production of PIF and FUF.

Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.

Protein phosphatase 2A (PP2A) is an abundant heterotrimeric holoenzyme in eukaryotic cells coordinating with specific kinases to regulate spatial-temporal protein dephosphorylation in various biological processes. However, the function of PP2A in cortical neurogenesis remains largely unknown. Here, we report that neuronal-specific deletion of Pp2acα in mice displayed microcephaly, with significantly smaller brains and defective learning and memory ability. Mechanistically, neuronal Pp2acα deficiency resulted in elevated endogenous DNA damage and activation of ATR/CHK1 signaling. It was further induced by the loss of direct interaction between PP2AC and ATR as well as the function of PP2AC to dephosphorylate ATR. Importantly, ATR/CHK1 signaling dysregulation altered both the expression and activity of several critical downstream factors including P53, P21, Bcl2, and Bax, which led to decreased proliferation of cortical progenitor cells and increased apoptosis in developing cortical neurons. Taken together, our results indicate an essential function of PP2ACα in endogenous DNA damage response-mediated ATR signaling during neurogenesis, and defective PP2ACα in neurons contributes to microcephaly.

MSE-VGG: A Novel Deep Learning Approach Based on EEG for Rapid Ischemic Stroke Detection.

Ischemic stroke is a type of brain dysfunction caused by pathological changes in the blood vessels of the brain which leads to brain tissue ischemia and hypoxia and ultimately results in cell necrosis. Without timely and effective treatment in the early time window, ischemic stroke can lead to long-term disability and even death. Therefore, rapid detection is crucial in patients with ischemic stroke. In this study, we developed a deep learning model based on fusion features extracted from electroencephalography (EEG) signals for the fast detection of ischemic stroke. Specifically, we recruited 20 ischemic stroke patients who underwent EEG examination during the acute phase of stroke and collected EEG signals from 19 adults with no history of stroke as a control group. Afterwards, we constructed correlation-weighted Phase Lag Index (cwPLI), a novel feature, to explore the synchronization information and functional connectivity between EEG channels. Moreover, the spatio-temporal information from functional connectivity and the nonlinear information from complexity were fused by combining the cwPLI matrix and Sample Entropy (SaEn) together to further improve the discriminative ability of the model. Finally, the novel MSE-VGG network was employed as a classifier to distinguish ischemic stroke from non-ischemic stroke data. Five-fold cross-validation experiments demonstrated that the proposed model possesses excellent performance, with accuracy, sensitivity, and specificity reaching 90.17%, 89.86%, and 90.44%, respectively. Experiments on time consumption verified that the proposed method is superior to other state-of-the-art examinations. This study contributes to the advancement of the rapid detection of ischemic stroke, shedding light on the untapped potential of EEG and demonstrating the efficacy of deep learning in ischemic stroke identification.

Critical radius prediction for small radius curved section of two-lane secondary highways based on speed characteristics.

Small radius curved sections of two-lane secondary highways have low technical indicators, complex alignments, and frequent accidents. In order to improve the safety of traffic operation, the article investigates the curved sections of two-lane secondary highways with different radii and obtains the travelling speeds of different vehicle types at different section locations. By studying the trajectory characteristics and speed characteristics of vehicles travelling in curves, the velocity difference ratio, which responds to the continuity of driving speed, was defined. Then, based on this, this paper investigates the vehicle motion law of small radius curved road sections. The results show that the speed change of large cars in small radius curves is similar to a "U" shape, while the speed change of small cars is similar to a "V" shape. The speed adjustments of the larger cars occur mainly within the range of gentle curves, whereas the speed changes of the smaller cars are large throughout the range of curves. There is a significant exponential function relationship between curve radius and 85 % percentile speed, from which the curve radius threshold can be predicted. This provides a basis for engineering construction of curved road sections and optimization of curve design indicators, which greatly improves the traffic safety level of curved road sections.

Designing a Robust Ni-P/CeO2 Superhydrophobic Composite Coating for Synergistically Enhanced Corrosion Protection and Friction Reduction Performance.

Superhydrophobic surfaces have received widespread attention for their unique hydrophobicity in metal corrosion protection. However, the shortcomings of mechanical stability and long-term corrosion resistance limit their practical application. In this work, we designed and fabricated an anticorrosive and friction reducing Ni-P/CeO2 superhydrophobic composite (SC) coating on a copper surface. The fabricated coating shows good superhydrophobicity with a water contact angle of up to 154°. The Ni-P support structure and CeO2 nanoparticles form a multilayer micro/nanostructure by electrodeposition, ensuring excellent mechanical stability of the Ni-P/CeO2 SC coating. Electrochemical tests indicate that the coating has excellent corrosion resistance due to the superhydrophobic air film, Ni-P barrier layer, and CeO2 inhibition. Moreover, the friction coefficient of the coating is only 0.11 under dry friction conditions, showing excellent friction-reducing performance, which is attributed to the cooperation of the low adhesion coefficient of superhydrophobic surfaces, the ball-rolling effect of CeO2 nanoparticles, and the self-healing effect of the Ni-P micro/nanostructure. This work provides a novel strategy for designing a robust superhydrophobic coating with mechanical stability, corrosion protection, and friction reduction abilities to inspire new applications of superhydrophobic surfaces.

Empowering Photovoltaic Panel Anti-Icing: Superhydrophobic Organic Composite Coating with In Situ Photothermal and Transparency.

Solar energy is widely used in photovoltaic power generation as a kind of clean energy. However, the liquid film, frosting, and icing on the photovoltaic module seriously limit the efficiency of photovoltaic power generation. We developed a composite coating (Y6-NanoSH) by combining an in situ photothermal and transparent Y6 organic film with a nanosuperhydrophobic material. The Y6-NanoSH coated glass exhibited excellent optical clarity both indoors and outdoors, indicating that the coating holds great promise in anti-icing applications for photovoltaic panels. The Y6-NanoSH coating absorbs very little visible light but instead absorbs in the near-infrared region, thereby emitting heat. When exposed to sunlight, the Y6-NanoSH coated photovoltaic panel raises its surface temperature, inhibiting the growth and accumulation of ice and frost on its surface. This is achieved through a combination of photothermal emission and superhydrophobic repellency, which promotes the evaporation and rolling away of water droplets. This validates our success in developing a photothermal, transparent, and superhydrophobic coating with excellent anti-icing capabilities, suitable for use on photovoltaic panels, as well as potential applications in car windscreens, transmission lines, curtain walls, and weather radomes.

Highly Sensitive Flexible Capacitive Pressure Sensor Based on a Multicross-Linked Dual-Network Ionic Hydrogel for Blood Pressure Monitoring Applications.

Flexible capacitive pressure sensors based on ionic hydrogels (IHs) have garnered significant attention in the field of wearable technology. However, the vulnerability of traditional single-network hydrogels to mechanical damage and the complexity associated with preparing double-network hydrogels present challenges in developing a highly sensitive, easily prepared, and durable IH-based flexible capacitive pressure sensor. This study introduces a novel multicross-linked dual-network IH achieved through the physical and chemical cross-linking of polymers polyvinyl alcohol (PVA) and chitosan (CS), ionic solution H3PO4, and cross-linking agent gum arabic. Flexible capacitive pressure sensors, characterized by high sensitivity and a broad pressure range, are fabricated by employing mesh as templates to design cut-corner cube microstructures with high uniformity and controllability on the IHs. The sensor exhibits high sensitivity across a wide pressure range (0-290 kPa) and with excellent features such as high resolution (∼1.3 Pa), fast response-recovery time (∼11 ms), and repeatable compression stability at 25 kPa (>2000 cycles). The IHs as a dielectric layer demonstrate long-term water retention properties, enabling exposure to air for up to 100 days. Additionally, the developed sensor shows the ability to accurately measure the pulse wave within the small pressure range. By combining the pulse wave acquired by the sensor with a trained neural network model, we achieve successful blood pressure (BP) prediction, meeting the standards set by the Association for the Advancement of Medical Instrumentation and the British Hypertension Society. Ultimately, the sensor proposed in this study holds promising prospects for broad applications in high-precision wearable medical electronic devices.

Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology.

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.

Evolution of ferromagnetic cluster in perovskite La0.88Sr0.12MnO3 nanocrystalline detected by EPR spectrum.

Electron paramagnetic resonance (EPR) studies were performed on La0.88Sr0.12MnO3 (LSMO) nanocrystalline together with the measurement of its magnetization. Various spectrum parameters including line width, effective g-value and double-integrated intensities have been analyzed in detail. We found nonlinear behavior occurred in the inverse susceptibility far above the Curie temperature TC, indicating short-range ferromagnetic (FM) clusters and Griffiths-like phase behavior in the paramagnetic (PM) phase. Based on the variation of EPR spectra, except for a typical PM resonance peak, an extra resonance signal was observed in the lower field region and developed as temperature decreased from 320 K to 110 K, which gave a direct evidence of the existence of FM cluster in the PM region of LSMO nanocrystalline. We proposed that the appearance of the Griffiths phase was due to the short FM correlation in the PM regime enhanced by surface spin ordering.

LUX ARRHYTHMO links CBF pathway and jasmonic acid metabolism to regulate cold tolerance of tea plants.

Cold stress declines the quality and yield of tea, yet the molecular basis underlying cold tolerance of tea plants (Camellia sinensis) remains largely unknown. Here, we identified a circadian rhythm component LUX ARRHYTHMO (LUX) that potentially regulates cold tolerance of tea plants through a genome-wide association study and transcriptomic analysis. The expression of CsLUX phased with sunrise and sunset and was strongly induced by cold stress. Genetic assays indicated that CsLUX is a positive regulator of freezing tolerance in tea plants. CsLUX was directly activated by CsCBF1 and repressed the expression level of CsLOX2, which regulates the cold tolerance of tea plants through dynamically modulating jasmonic acid content. Furthermore, we showed that the CsLUX-CsJAZ1 complex attenuated the physical interaction of CsJAZ1 with CsICE1, liberating CsICE1 with transcriptional activities to withstand cold stress. Notably, a single-nucleotide variation of C-to-A in the coding region of CsLUX was functionally validated as the potential elite haplotype for cold response, which provided valuable molecular markers for future cold resistance breeding in tea plants.

The comorbidity mechanism of problematic internet use and depression among Chinese college students: A cross-lagged panel network analysis.

Problematic internet use (PIU) and depression usually co-occur and are common among college students. According to network theory, it may be attributed to the interplay of symptoms that connect these two mental health problems. However, most studies have failed to examine complex and subtle connections at the symptom level and have not clarified how PIU and depression symptoms are intercorrelated, which symptoms serve as the source of comorbidity (i.e., the central symptoms), and whether such a comorbidity mechanism would change with higher grades. To explore these questions, this study examined four contemporaneous networks and three cross-lagged panel networks, visualizing the symptoms as nodes and the connections between symptoms as edges. A total of 2,420 college students (Mage = 18.35, SD = 0.84; 67.98 % girls) completed four annual surveys. Overall, the results of contemporaneous networks and cross-lagged panel networks indicated that (a) PIU and depression symptoms are intercorrelated; (b) the core symptoms responsible for comorbidity mostly belonged to PIU, and (c) the comorbidity mechanism would change with time. These findings explain the dynamic relation between PIU and depression and identify possible primary symptoms that comorbidity programs can mitigate at different stages of the college years.