Citrulline facilitates the glycolysis, proliferation, and metastasis of lung cancer cells by regulating RAB3C.

Lung cancer (LC) is one of the major malignant diseases threatening human health. The study aimed to identify the effect of citrulline on the malignant phenotype of LC cells and to further disclose the potential molecular mechanism of citrulline in regulating the development of LC, providing a novel molecular biological basis for the clinical treatment of LC. The effects of citrulline on the viability, proliferation, migration, and invasion of LC cells (A549, H1299) were validated by CCK-8, colony formation, EdU, and transwell assays. The cell glycolysis was assessed via determining the glucose uptake, lactate production, ATP levels, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). RNA-seq and molecular docking were performed to screen for citrulline-binding target proteins. Western blotting experiments were conducted to examine the expression of related signaling pathway molecules. In addition, the impacts of citrulline on LC growth in vivo were investigated by constructing mouse models. Citrulline augmented the viability of LC cells in a concentration and time-dependent manner. The proliferation, migration, invasion, glycolysis, and EMT processes of LC cells were substantially enhanced after citrulline treatment. Bioinformatics analysis indicated that citrulline could bind to RAB3C protein. Western blotting results indicated that citrulline activated the IL-6/STAT3 pathway by binding to RAB3C. In addition, animal experiments disclosed that citrulline promoted tumor growth in mice. Citrulline accelerated the glycolysis and activated the IL6/STAT3 pathway through the RAB3C protein, consequently facilitating the development of LC.

Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation.

BACKGROUND: Meteorin-like protein (METRNL)/Interleukin-41 (IL-41) is a novel immune-secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD). METHODS: METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903-induced AD-like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single-cell RNA-seq and RNA-seq. RESULTS: METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced ß-Catenin activation, limited the expression of Th2-related molecules that attract the accumulation of Arginase-1 (Arg1)hi macrophages, dendritic cells, and activated mast cells. CONCLUSIONS: METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule ß-Catenin.

Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Fast Reaction Kinetics and Commendable Low-Temperature Adaptability of Zinc Batteries Enabled by Aprotic Water-Acetamide Symbiotic Solvation Sheath.

Although rechargeable aqueous zinc batteries are cost effectiveness, intrinsicly safe, and high activity, they are also known for bringing rampant hydrogen evolution reaction and corrosion. While eutectic electrolytes can effectively eliminate these issues, its high viscosity severely reduces the mobility of Zn2+ ions and exhibits poor temperature adaptability. Here, we infuse acetamide molecules with Lewis base and hydrogen bond donors into a solvated shell of Zn[(H2 O)6 ]2+ to create Zn(H2 O)3 (ace)(BF4 )2 . The viscosity of 1ace-1H2 O is 0.032 Pa s, significantly lower than that of 1ace-0H2 O (995.6 Pa s), which improves ionic conductivity (9.56 mS cm-1 ) and shows lower freezing point of -45 °C, as opposed to 1ace-0H2 O of 4.04 mS cm-1 and 12 °C, respectively. The acidity of 1ace-1H2 O is ≈2.8, higher than 0ace-1H2 O at ≈0.76, making side reactions less likely. Furthermore, benefiting from the ZnCO3 /ZnF2 -rich organic/inorganic solid electrolyte interface, the Zn || Zn cells cycle more than 1300 hours at 1 mA cm-2 , and the Zn || Cu operated over 1800 cycles with an average Coulomb efficiency of ≈99.8 %. The Zn || PANI cell cycled over 8500 cycles, with a specific capacity of 99.8 mAh g-1 at 5 A g-1 at room temperature, and operated at -40 °C with a capacity of 66.8 mAh g-1 .

Research on the application of Thelephora ganbajun exopolysaccharides in antioxidant, anti-inflammatory and spot-fading cosmetics.

Thelephora ganbajun exopolysaccharides (TGEP) with a "coral-like" branched chain structure (main chain diameter âˆ¼ 80 nm) were prepared by liquid fermentation and fractionated by ion-exchange chromatography. The main fraction (TGEP-2) with the highest in vitro antioxidant capacity was composed of Glc, Man, Gal, GalA, GlcA, Ara, Rha, GlcN, Fuc and Rib in a molar ratio of 465.43:420.43:219.14:188.43:37:35.14:31.43:19.43:11.14:1, with a molecular weight of 1.879 × 104 Da. The sequence of monosaccharide residue release revealed that Gal, Glc and Ara residues were more distributed in the side-branch chains and at their ends, whereas Man and GalA residues were more distributed in the main chains. TGEP-2 contained linear residues (mainly →4)-Glcp-(1 â†’ and →4)-Manp-(1→), branch residues (→3,6)-Glcp-(1→, →4,6)-Glcp-(1 â†’ and →3,6)-Galp-(1→) and terminal residues (Galp-(1→, Manp-(1 â†’ and Glcp-(1→). TGEP-2 consisted of α- and ß-glycosidically linked pyranosides, with a triple helical conformation and many long branches. Zebrafish oxidative stress and inflammation models found that TGEP-2 had antioxidant and anti-inflammatory activities. The zebrafish skin black spot assay showed that TGEP-2 inhibited melanin formation. Therefore, extracellular polysaccharides of T. ganbajun have strong application potential in anti-oxidant, anti-inflammatory and skin spot-fading functions cosmetics.

Comprehensive analysis of biological landscape of oxidative stress-related genes in diabetic erectile dysfunction.

Oxidative stress plays a pivotal role in the pathogenesis of diabetic erectile dysfunction, while specific mechanisms have not been illuminated. The study aims to reveal the genetic expression patterns of oxidative stress in diabetic erectile dysfunction. Transcriptome data of diabetic erectile dysfunction and oxidative stress-related genes (OSRGs) in the Gene Expression Omnibus database were downloaded and analyzed based on differential expression. Functional enrichment analyses were conducted to clarify the biological functions. A protein interaction framework was established, and significant gene profiles were validated in the cavernous endothelial cells, clinical patients, and rat models. A miRNA-OSRGs network was predicted and validated. The results were analyzed using Student's t-test. The analysis screened 203 differentially expressed OSRGs (p < 0.05), which had a close association with oxidoreductase activities, glutathione metabolism, and autophagy. A four-gene signature comprised of EPS8L2 (p = 0.044), GSTA3 (p = 0.015), LOX (p < 0.001) and MGST1 (p = 0.002) was well validated and regarded as the hub OSRGs. Compared with the control group, notable increases and decreases were observed in the expressions of GSTA3 (3.683 ± 0.636 vs. 0.416 ± 0.507) and LOX (2.104 ± 1.895 vs. 18.804 ± 2.751) in the validated diabetic erectile dysfunction group. The hub OSRGs-related miRNAs participated in smooth muscle cell proliferation. Besides, miR-125a-3p (p = 0.034) and miR-138-2-3p (p = 0.012) were validated as promising oxidative stress-related miRNA biomarkers. Our findings revealed the genetic alternations of oxidative stress in diabetic erectile dysfunction. These results will be instructive to explore the molecular landscape and the potential treatment for diabetic erectile dysfunction.

Exploring potential genes and mechanisms linking erectile dysfunction and depression.

Background: The clinical correlation between erectile dysfunction (ED) and depression has been revealed in cumulative studies. However, the evidence of shared mechanisms between them was insufficient. This study aimed to explore common transcriptomic alterations associated with ED and depression. Materials and methods: The gene sets associated with ED and depression were collected from the Gene Expression Omnibus (GEO) database. Comparative analysis was conducted to obtain common genes. Using R software and other appropriate tools, we conducted a range of analyses, including function enrichment, interactive network creation, gene cluster analysis, and transcriptional and post-transcriptional signature profiling. Candidate hub crosslinks between ED and depression were selected after external validation and molecular experiments. Furthermore, subpopulation location and disease association of hub genes were explored. Results: A total of 85 common genes were identified between ED and depression. These genes strongly correlate with cell adhesion, redox homeostasis, reactive oxygen species metabolic process, and neuronal cell body. An interactive network consisting of 80 proteins and 216 interactions was thereby developed. Analysis of the proteomic signature of common genes highlighted eight major shared genes: CLDN5, COL7A1, LDHA, MAP2K2, RETSAT, SEMA3A, TAGLN, and TBC1D1. These genes were involved in blood vessel morphogenesis and muscle cell activity. A subsequent transcription factor (TF)-miRNA network showed 47 TFs and 88 miRNAs relevant to shared genes. Finally, CLDN5 and TBC1D1 were well-validated and identified as the hub crosslinks between ED and depression. These genes had specific subpopulation locations in the corpus cavernosum and brain tissue, respectively. Conclusion: Our study is the first to investigate common transcriptomic alterations and the shared biological roles of ED and depression. The findings of this study provide insights into the referential molecular mechanisms underlying the co-existence between depression and ED.

Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.

Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3ß axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily oscillations in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.

Mmp14 is required for matrisome homeostasis and circadian rhythm in fibroblasts.

The circadian clock in tendon regulates the daily rhythmic synthesis of collagen-I and the appearance and disappearance of small-diameter collagen fibrils in the extracellular matrix. How the fibrils are assembled and removed is not fully understood. Here, we first showed that the collagenase, membrane type I-matrix metalloproteinase (MT1-MMP, encoded by Mmp14), is regulated by the circadian clock in postnatal mouse tendon. Next, we generated tamoxifen-induced Col1a2-Cre-ERT2::Mmp14 KO mice (Mmp14 conditional knockout (CKO)). The CKO mice developed hind limb dorsiflexion and thickened tendons, which accumulated narrow-diameter collagen fibrils causing ultrastructural disorganization. Mass spectrometry of control tendons identified 1195 proteins of which 212 showed time-dependent abundance. In Mmp14 CKO mice 19 proteins had reversed temporal abundance and 176 proteins lost time dependency. Among these, the collagen crosslinking enzymes lysyl oxidase-like 1 (LOXL1) and lysyl hydroxylase 1 (LH1; encoded by Plod2) were elevated and had lost time-dependent regulation. High-pressure chromatography confirmed elevated levels of hydroxylysine aldehyde (pyridinoline) crosslinking of collagen in CKO tendons. As a result, collagen-I was refractory to extraction. We also showed that CRISPR-Cas9 deletion of Mmp14 from cultured fibroblasts resulted in loss of circadian clock rhythmicity of period 2 (PER2), and recombinant MT1-MMP was highly effective at cleaving soluble collagen-I but less effective at cleaving collagen pre-assembled into fibrils. In conclusion, our study shows that circadian clock-regulated Mmp14 controls the rhythmic synthesis of small diameter collagen fibrils, regulates collagen crosslinking, and its absence disrupts the circadian clock and matrisome in tendon fibroblasts.

Macromolecular condensation buffers intracellular water potential.

Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2,3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.

Flexible tactile sensors with biomimetic microstructures: Mechanisms, fabrication, and applications.

In recent years, flexible devices have gained rapid development with great potential in daily life. As the core component of wearable devices, flexible tactile sensors are prized for their excellent properties such as lightweight, stretchable and foldable. Consequently, numerous high-performance sensors have been developed, along with an array of innovative fabrication processes. It has been recognized that the improvement of the single performance index for flexible tactile sensors is not enough for practical sensing applications. Therefore, balancing and optimization of overall performance of the sensor are extensively anticipated. Furthermore, new functional characteristics are required for practical applications, such as freeze resistance, corrosion resistance, self-cleaning, and degradability. From a bionic perspective, the overall performance of a sensor can be optimized by constructing bionic microstructures which can deliver additional functional features. This review briefly summarizes the latest developments in bionic microstructures for different types of tactile sensors and critically analyzes the sensing performance of fabricated flexible tactile sensors. Based on this, the application prospects of bionic microstructure-based tactile sensors in human detection and human-machine interaction devices are introduced.

The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc.

The circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks which control ∼6% of the transcriptome in a rhythmic manner, including key genes involved in extracellular matrix (ECM) homeostasis. However, it remains largely unknown to what extent the local IVD molecular clock is required to drive rhythmic gene transcription and IVD physiology. In this work, we identified profound age-related changes of ECM microarchitecture and an endochondral ossification-like phenotype in the annulus fibrosus (AF) region of the IVD in the Col2a1-Bmal1 knockout mice. Circadian time series RNA-Seq of the whole IVD in Bmal1 knockout revealed loss of circadian patterns in gene expression, with an unexpected emergence of 12 h ultradian rhythms, including FOXO transcription factors. Further RNA sequencing of the AF tissue identified region-specific changes in gene expression, evidencing a loss of AF phenotype markers and a dysregulation of ECM and FOXO pathways in Bmal1 knockout mice. Consistent with an up-regulation of FOXO1 mRNA and protein levels in Bmal1 knockout IVDs, inhibition of FOXO1 in AF cells suppressed their osteogenic differentiation. Collectively, these data highlight the importance of the local molecular clock mechanism in the maintenance of the cell fate and ECM homeostasis of the IVD. Further studies may identify potential new molecular targets for alleviating IVD degeneration.

Subtype-specific circadian clock dysregulation modulates breast cancer biology, invasiveness, and prognosis.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular rhythms in non-cancerous and cancerous human breast tissues are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For non-cancerous tissue, the inferred order of core-circadian genes matches established physiology. Inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of Luminal A samples exhibit continued, albeit disrupted rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among Luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude Luminal A tumors. Patients with high-magnitude tumors had reduced 5-year survival. Correspondingly, 3D Luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl4 treatment. Our data demonstrate that disruption to circadian rhythm primes HSCs towards an accelerated fibrotic response which worsens liver disease.

Tick tock, the cartilage clock.

Osteoarthritis (OA) is the most common age-related joint disease, affecting articular cartilage and other joint structures, causing severe pain and disability. Due to a limited understanding of the underlying disease pathogenesis, there are currently no disease-modifying drugs for OA. Circadian rhythms are generated by cell-intrinsic timekeeping mechanisms which are known to dampen during ageing, increasing disease risks. In this review, we focus on one emerging area of chondrocyte biology, the circadian clocks. We first provide a historical perspective of circadian clock discoveries and the molecular underpinnings. We will then focus on the expression and functions of circadian clocks in articular cartilage, including their rhythmic target genes and pathways, links to ageing, tissue degeneration, and OA, as well as tissue niche-specific entrainment pathways. Further research into cartilage clocks and ageing may have broader implications in the understanding of OA pathogenesis, the standardization of biomarker detection, and the development of novel therapeutic routes for the prevention and management of OA and other musculoskeletal diseases.

The circadian clock and extracellular matrix homeostasis in aging and age-related diseases.

The extracellular matrix (ECM) is the noncellular scaffolding component present within all tissues and organs. It provides crucial biochemical and biomechanical cues to instruct cellular behavior and has been shown to be under circadian clock regulation, a highly conserved cell-intrinsic timekeeping mechanism that has evolved with the 24-hour rhythmic environment. Aging is a major risk factor for many diseases, including cancer, fibrosis, and neurodegenerative disorders. Both aging and our modern 24/7 society disrupt circadian rhythms, which could contribute to altered ECM homeostasis. Understanding the daily dynamics of ECM and how this mechanism changes with age will have a profound impact on tissue health, disease prevention, and improving treatments. Maintaining rhythmic oscillations has been proposed as a hallmark of health. On the other hand, many hallmarks of aging turn out to be key regulators of circadian timekeeping mechanisms. In this review, we summarize new work linking the ECM with circadian clocks and tissue aging. We discuss how the changes in the biomechanical and biochemical properties of ECM during aging may contribute to circadian clock dysregulation. We also consider how the dampening of clocks with age could compromise the daily dynamic regulation of ECM homeostasis in matrix-rich tissues. This review aims to encourage new concepts and testable hypotheses about the two-way interactions between circadian clocks and ECM in the context of aging.

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome.

Background: Clinical associations between erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been noticed, but the common pathogenic mechanisms between them remain elusive. The aim of the study was to mine shared genetic alterations between ED and chronic prostatitis/chronic pelvic pain syndrome. Method: Transcriptome data of ED and chronic prostatitis/chronic pelvic pain syndrome-related genes (CPRGs) were retrieved from relevant databases and differentially expressed analysis was used to obtain significant CPRGs. Then function enrichment and interaction analyses were performed to show shared transcriptional signature, including gene ontology and pathway enrichment, the construction of protein-protein interaction (PPI) network, cluster analysis, and co-expression analysis. Hub CPRGs and key cross-link were selected by validating these genes in clinical samples, chronic prostatitis/chronic pelvic pain syndrome and ED-related datasets. Then the miRNA-OSRGs co-regulatory network was predicted and validated. Subpopulation distribution and disease association of hub CPRGs were further identified. Result: Differentially expressed analysis revealed 363 significant CPRGs between ED and chronic prostatitis/chronic pelvic pain syndrome, functioning in inflammatory reaction, oxidative stress, apoptosis, smooth muscle cell proliferation, and extracellular matrix organization. A PPI network containing 245 nodes and 504 interactions was constructed. Module analysis depicted that multicellular organismal process and immune metabolic process were enriched. 17 genes were screened in PPI via topological algorithms, and reactive oxygen species as well as interleukin-1 metabolism were regarded as the bridging interactive mechanism. After screening and validation, a hub-CPRG signature consisting of COL1A1, MAPK6, LPL, NFE2L2 and NQO1 were identified and associated miRNA were verified. These miRNAs played an important role in immune and inflammatory response likewise. Finally, NQO1 was identified as a key genetic link between ED and chronic prostatitis/chronic pelvic pain syndrome. It was predominately enriched in corpus cavernosum endothelial cell, and correlated with other male urogenital and immune system diseases tightly. Conclusion: We identified the genetic profiles as well as corresponding regulatory network underlying interaction between ED and chronic prostatitis/chronic pelvic pain syndrome via multi-omics analysis. These findings expanded a new understanding for the molecular mechanism of ED with chronic prostatitis/chronic pelvic pain syndrome.

Directed differentiation of hPSCs through a simplified lateral plate mesoderm protocol for generation of articular cartilage progenitors.

Developmentally, the articular joints are derived from lateral plate (LP) mesoderm. However, no study has produced both LP derived prechondrocytes and preosteoblasts from human pluripotent stem cells (hPSC) through a common progenitor in a chemically defined manner. Differentiation of hPSCs through the authentic route, via an LP-osteochondral progenitor (OCP), may aid understanding of human cartilage development and the generation of effective cell therapies for osteoarthritis. We refined our existing chondrogenic protocol, incorporating knowledge from development and other studies to produce a LP-OCP from which prechondrocyte- and preosteoblast-like cells can be generated. Results show the formation of an OCP, which can be further driven to prechondrocytes and preosteoblasts. Prechondrocytes cultured in pellets produced cartilage like matrix with lacunae and superficial flattened cells expressing lubricin. Additionally, preosteoblasts were able to generate a mineralised structure. This protocol can therefore be used to investigate further cartilage development and in the development of joint cartilage for potential treatments.

Highly sensitive detection of low-concentration sodium chloride solutions based on polymeric nanofilms coated long period fiber grating.

Long period fiber gratings (LPFGs) have special advantages in the detection of salt concentrations due to small volume, corrosion resistance and immunity to electromagnetic interference. However, it is very difficult to distinguish low-concentration salt solutions with usual LPFGs owing to the poor sensitivity. In this paper, the detection capability of the LPFG to low-concentration salt solutions was significantly improved by assembling salt-containing poly (diallyldimethylammonium chloride) (PDDA) and salt-containing poly (sodium-p-styrenesulfonate) (PSS). Experimental results showed that, the responsive wavelength range of the LPFG was remarkably broadened in low-concentration salt solutions after assembling nanofilms. The suitable detection range of the PDDA/PSS films coated LPFG for salt concentrations was 0-3%. In such a range, the average refractive index sensitivity and the average salinity sensitivity of the LPFG was as high as 29545.9 nm/RIU and 52.2 nm/% respectively. Compared with the LPFG without nanofilms, the discrimination ability of the PDDA/PSS films coated LPFG to 0-3% salt solutions increased by 568 times. The analysis demonstrated that PDDA and salt in the assembly solutions played a pivotal role in the above effects. The proposed sensor has extensive application prospects in the monitoring of salt concentration in many fields such as seawater, food processing, fermentation process, etc.