Mrc1 regulates parental histone segregation and heterochromatin inheritance.

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.

NHX5/NHX6/SPY22 complex regulates BRI1 and brassinosteroid signaling in Arabidopsis.

NHX5 and NHX6, Arabidopsis endosomal antiporters, play a vital role in facilitating ion and pH homeostasis in endosomal compartments. Studies have found that NHX5 and NHX6 are essential for protein trafficking, auxin homeostasis, and plant growth and development. Here, we report the role of NHX5 and NHX6 in brassinosteroid (BR) signaling. We found that hypocotyl growth was enhanced in nhx5 nhx6 under epibrassinolide (eBR) treatment. nhx5 nhx6 bri1 was insensitive to eBR treatment, indicating that NHX5 and NHX6 are downstream of the BRI1 receptor in BR signaling. Moreover, confocal observation with both hypocotyls and root tips showed that BRI1-YFP localization in the plasma membrane (PM) was reduced in nhx5 nhx6. Interestingly, brefeldin A (BFA) treatment showed that formation of the BFA bodies containing BRI1 and their disassembling were disrupted in nhx5 nhx6. Further genetic analysis showed that NHX5/NHX6 and SYP22 may act coordinately in BR signaling. NHX5 and NHX6 may regulate SYP22 function by modulating cellular K+ and pH homeostasis. Importantly, NHX5 and NHX6 colocalize and interact with SYP22, but do not interact with BRI1. In summary, our findings indicate that NHX5/NHX6/SYP22 complex is essential for the regulation of BRI1 recycling and PM localization. The H+-leak facilitated by NHX5 and NHX6 offers a means of controlling BR signaling in plants.

High-purity La3-xTe4 Material with Superior Thermoelectric Performance Synthesized via Te-vapor Transport and Solid-State Diffusion.

La3-xTe4 is a very promising high-temperature candidate applied in next-generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high-energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te-vapor transport and solid-phase diffusion to efficiently produce the RE3-xTe4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high-energy ball-milling instruments, conventionally indispensable in the mechanochemical syntheses. For as-synthesized La2.74Te4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated.

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Near Ultraviolet-Excitable Cyan-Emissive Hybrid Copper(I) Halides Nonlinear Optical Crystals with Near-Unity Photoluminescence Quantum Yield and High-Efficiency X-ray Scintillation.

Designing and synthesizing multifunctional hybrid copper halides with near ultraviolet (NUV) light-excited high-energy emission (< 500 nm) remains challenging. Here, a pair of broadband-excited high-energy emitting isomers, namely, α-/ß-(MePh3P)2CuI3 (MePh3P = methyltriphenylphosphonium), were synthesized. α-(MePh3P)2CuI3 with blue emission peaking at 475 nm is firstly discovered wherein its structure contains regular [CuI3]2‒ triangles and crystallizes in centrosymmetric space group P21/c. While ß-(MePh3P)2CuI3 featuring distorted [CuI3]2‒ planar triangles shows inversion symmetry breaking and crystallizes in the noncentrosymmetric space group P21, which exhibits cyan emission peaking at 495 nm with prominent near-unity photoluminescence quantum yield and the excitation band ranging from 200 to 450 nm. Intriguingly, ß-(MePh3P)2CuI3 exhibits phase-matchable second-harmonic generation response of 0.54 × KDP and a suitable birefringence of 0.06@1064 nm. Furthermore, ß-(MePh3P)2CuI3 also can be excited by X-ray radioluminescence with a high scintillation light yield of 16193 photon/MeV and an ultra-low detection limit of 47.97 nGy/s, which is only 0.87% of the standard medical diagnosis (5.5 µGy/s). This work not only promotes the development of solid-state lighting, laser frequency conversion and X-ray imaging, but also provides a reference for constructing multifunctional hybrid metal halides.

Long Noncoding RNAs in Response to Hyperosmolarity Stress, but Not Salt Stress, Were Mainly Enriched in the Rice Roots.

Due to their immobility and possession of underground parts, plants have evolved various mechanisms to endure and adapt to abiotic stresses such as extreme temperatures, drought, and salinity. However, the contribution of long noncoding RNAs (lncRNAs) to different abiotic stresses and distinct rice seedling parts remains largely uncharacterized beyond the protein-coding gene (PCG) layer. Using transcriptomics and bioinformatics methods, we systematically identified lncRNAs and characterized their expression patterns in the roots and shoots of wild type (WT) and ososca1.1 (reduced hyperosmolality-induced [Ca2+]i increase in rice) seedlings under hyperosmolarity and salt stresses. Here, 2937 candidate lncRNAs were identified in rice seedlings, with intergenic lncRNAs representing the largest category. Although the detectable sequence conservation of lncRNAs was low, we observed that lncRNAs had more orthologs within the Oryza. By comparing WT and ososca1.1, the transcription level of OsOSCA1.1-related lncRNAs in roots was greatly enhanced in the face of hyperosmolality stress. Regarding regulation mode, the co-expression network revealed connections between trans-regulated lncRNAs and their target PCGs related to OsOSCA1.1 and its mediation of hyperosmolality stress sensing. Interestingly, compared to PCGs, the expression of lncRNAs in roots was more sensitive to hyperosmolarity stress than to salt stress. Furthermore, OsOSCA1.1-related hyperosmolarity stress-responsive lncRNAs were enriched in roots, and their potential cis-regulated genes were associated with transcriptional regulation and signaling transduction. Not to be ignored, we identified a motif-conserved and hyperosmolarity stress-activated lncRNA gene (OSlncRNA), speculating on its origin and evolutionary history in Oryza. In summary, we provide a global perspective and a lncRNA resource to understand hyperosmolality stress sensing in rice roots, which helps to decode the complex molecular networks involved in plant sensing and adaptation to stressful environments.

A Transcriptomic and Metabolomic Study on the Biosynthesis of Iridoids in Phlomoides rotata from the Qinghai-Tibet Plateau.

Phlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1, IDI1, 8-HGO1, and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata. The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata.

Risk factors for noncarious cervical lesions: A case-control study.

OBJECTIVES: Noncarious cervical lesions (NCCLs) are multifactorial and can be caused by the anatomical structure of the teeth, erosion, abrasion and abnormal occlusion. The aim of this case-control study was to explore the risk factors for NCCLs. METHODS: Cone-beam computed tomography was used to determine whether a wedge-shaped defect existed at the cementoenamel junction. We compared 63 participants with NCCLs with 63 controls without NCCLs, matched for sex, age (±1 year) and toothbrushing-related factors (e.g., type of bristle and brushing patterns, frequency and strength). All participants were asked to complete a questionnaire about self-administered daily diet habits and health condition. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for NCCLs. RESULTS: Significant variables in the univariate analysis (i.e., p < .2) included frequency of carbonated beverage consumption, sella-nasion-point B angle (SNB) and Frankfort-mandibular plane angle (FMA). Multivariate logistic regression demonstrated that the consumption frequency of carbonated beverages (odds ratio [OR] = 3.147; 95% confidence interval [CI], 1.039-9.532), FMA (OR = 1.100; 95% CI, 1.004-1.204) and SNB (OR = 0.896; 95% CI, 0.813-0.988) was independent influencing factors. The area under the receiver operating characteristic curve (AUC) value of regression Model 1 (established with the frequency of carbonated beverage consumption, FMA, SNB and sleep bruxism) was 0.700 (95% CI, 0.607-0.792; p < .001), and that of regression Model 2 (established using the frequency of carbonated beverage consumption, FMA and SNB) was 0.704 (95% CI, 0.612-0.796; p < .001). CONCLUSIONS: The consumption frequency of carbonated beverages and FMA was risk factors for NCCLs; the higher the frequency of carbonated beverage consumption and FMA, the higher was the probability of NCCLs. SNB was a protective factor for NCCL occurrence; the larger the SNB, the lower was the probability of NCCL occurrence. These findings have further clarified the aetiology of NCCLs and provided clinicians with valuable insights into strategies for preventing the loss of dental tissue.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

Experimental study on the effect of different cement content on the improvement of dynamic characteristics of seismic-prone poor soil.

The improvement of sandy soils with poor seismic properties to modify their dynamic characteristics is of great importance in seismic design for engineering sites. In this study, a series of dynamic tests on sandy soils sandy soils with poor seismic conditions were conducted using the GCTS resonant column system to investigate the improvements effects of different cement contents on dynamic characteristic parameters. The research findings are as follows: The cement content has certain influences on the dynamic shear modulus, dynamic shear modulus ratio, the maximum dynamic shear modulus, and the damping ratio of sandy soils with poor seismic properties. Among them, the influence on dynamic shear modulus is limited, while the damping ratio is significantly affected. The addition of cement to seismic-poor sandy soils significantly enhances their dynamic characteristics. The most noticeable improvement is observed when the cement content is 8%. Through curve fitting analysis, a relationship equation is established between the maximum dynamic shear modulus and the cement content, and the relevant parameters are provided. A comparative test between the improved soils and the remolded soils reveals that the addition of cement significantly improves the seismic performance of the poor soils. The recommended values for the range of variation of the dynamic shear modulus ratio and damping ratio are provided, considering the effect of improvement. These research findings provide reference guidelines for seismic design and engineering sites.

Transcriptomic Profiles of Long Noncoding RNAs and Their Target Protein-Coding Genes Reveals Speciation Adaptation on the Qinghai-Xizang (Tibet) Plateau in Orinus.

Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nt, which lack the ability to encode proteins and are involved in multifarious growth, development, and regulatory processes in plants and mammals. However, the environmental-regulated expression profiles of lncRNAs in Orinus that may associated with their adaptation on the Qinghai-Xizang (Tibet) Plateau (QTP) have never been characterized. Here, we utilized transcriptomic sequencing data of two Orinus species (O. thoroldii and O. kokonoricus) to identify 1624 lncRNAs, including 1119 intergenic lncRNAs, 200 antisense lncRNAs, five intronic lncRNAs, and 300 sense lncRNAs. In addition, the evolutionary relationships of Orinus lncRNAs showed limited sequence conservation among 39 species, which implied that Orinus-specific lncRNAs contribute to speciation adaptation evolution. Furthermore, considering the cis-regulation mechanism, from 286 differentially expressed lncRNAs (DElncRNAs) and their nearby protein coding genes (PCGs) between O. thoroldii and O. kokonoricus, 128 lncRNA-PCG pairs were obtained in O. thoroldii, whereas 92 lncRNA-PCG pairs were obtained in O. kokonoricus. In addition, a total of 19 lncRNA-PCG pairs in O. thoroldii and 14 lncRNA-PCG pairs in O. kokonoricus were found to participate in different biological processes, indicating that the different expression profiles of DElncRNAs between O. thoroldii and O. kokonoricus were associated with their adaptation at different elevations on the QTP. We also found several pairs of DElncRNA nearby transcription factors (TFs), indicating that these DElncRNAs regulate the expression of TFs to aid O. thoroldii in adapting to the environment. Therefore, this work systematically identified a series of lncRNAs in Orinus, laying the groundwork for further exploration into the biological function of Orinus in environmental adaptation.

[Transcriptomic characteristics analysis of bone from chronic osteomyelitis].

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Inhibition of miR-199b-5p reduces pathological alterations in osteoarthritis by potentially targeting Fzd6 and Gcnt2.

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miR-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miR-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miR-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as potential target genes of MiR-199b-5p. Thus, these results indicated that MiR-199b-5p/Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA.

Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation mechanism in Phlomoides rotata from different habitats.

Phlomoides rotata is a traditional medical plant at 3100-5200 m altitude in the Tibet Plateau. In this study, flavonoid metabolites were investigated in P. rotata from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) habitats in Qinghai. The level of kaempferol 3-neohesperidoside, sakuranetin, and biochanin A was high in HN. The content of limocitrin and isoquercetin was high in YS. The levels of ikarisoside A and chrysosplenol D in GL were high. Schaftoside, miquelianin, malvidin chloride, and glabrene in CD exhibited high levels. The results showed a significant correlation between 59 flavonoids and 29 DEGs. Eleven flavonoids increased with altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, and HCT3 genes were crucial in regulating flavonoid biosynthesis. Three enzymes CHS, 4CL, and UFGT, were crucial in regulating flavonoid biosynthesis. This study provided biological and chemical evidence for the different uses of various regional plants of P. rotata.

Peripheral inflammation triggering central anxiety through the hippocampal glutamate metabolized receptor 1.

AIMS: This study aimed to investigate the relationship between ulcerative colitis (UC) and anxiety and explore its central mechanisms using colitis mice. METHODS: Anxiety-like behavior was assessed in mice induced by 3% dextran sodium sulfate (DSS) using the elevated plus maze and open-field test. The spatial transcriptome of the hippocampus was analyzed to assess the distribution of excitatory and inhibitory synapses, and Toll-like receptor 4 (TLR4) inhibitor TAK-242 (10 mg/kg) and AAV virus interference were used to examine the role of peripheral inflammation and central molecules such as Glutamate Receptor Metabotropic 1 (GRM1) in mediating anxiety behavior in colitis mice. RESULTS: DSS-induced colitis increased anxiety-like behaviors, which was reduced by TAK-242. Spatial transcriptome analysis of the hippocampus showed an excitatory-inhibitory imbalance mediated by glutamatergic synapses, and GRM1 in hippocampus was identified as a critical mediator of anxiety behavior in colitis mice via differential gene screening and AAV virus interference. CONCLUSION: Our work suggests that the hippocampus plays an important role in brain anxiety caused by peripheral inflammation, and over-excitation of hippocampal glutamate synapses by GRM1 activation induces anxiety-like behavior in colitis mice. These findings provide new insights into the central mechanisms underlying anxiety in UC and may contribute to the development of novel therapeutic strategies for UC-associated anxiety.

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance.

Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.

Hypoxia-induced miR-5100 promotes exosome-mediated activation of cancer-associated fibroblasts and metastasis of head and neck squamous cell carcinoma.

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.

Enhancing the Interaction of Carbon Nanotubes by Metal-Organic Decomposition with Improved Mechanical Strength and Ultra-Broadband EMI Shielding Performance.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

Association Between Number of Missing Teeth and Hyperlipidemia: The TCLSIH Cohort Study.

Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population. Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia. Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01). Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.