MCMV-infected maize attracts its insect vector Frankliniella occidentalis by inducing ß-myrcene.

Maize lethal necrosis is attributed to the accumulation of maize chlorotic mottle virus (MCMV), an invasive virus transmitted by insect vectors. The western flower thrips (WFT) can shift host to maize, thus promoting the spread of MCMV. However, our understanding of the characteristics and interactions involved in the transmission of MCMV is still limited. This study finds that non-viruliferous WFTs showed a 57.56% higher preference for MCMV-infected maize plants compared to healthy maize plants, while viruliferous WFTs showed a 53.70% higher preference for healthy maize plants compared to MCMV-infected maize plants. We also show for the first time that both adults and larvae of WFT could successfully acquire MCMV after 1 min of acquisition access period (AAP), and after 48 h of AAP, WFT could transmit MCMV in an inoculation access period of 1 h without a latent period. Both adults and larvae of WFT can transmit MCMV for up to 2 days. Furthermore, the decreasing number of viruliferous WFTs and transmission rates as time progressed, together with the transcriptomic evidence, collectively suggest that WFTs transmit MCMV in a semi-persistent method, a mode of transmission requiring minutes to several hours for acquisition access and having a retention time of several hours to a few days. Additionally, ß-myrcene can attract WFTs significantly and is detected in Nicotiana benthamiana plants transiently expressing MCMV CP (coat protein), which is consistent with results in MCMV-infected maize plants through the metabolomic profiling and the preference analyses of WFT. Therefore, this study demonstrates the indirect interaction between MCMV and WFT by inducing maize to synthesize ß-myrcene to attract insect vectors. The exploration of specific interactions between MCMV and WFT could help to expand the mechanism studies of virus-vector-host plant interaction and put forward a new insight for the combined control of MCMV and WFT through the manipulation of plant volatiles and key insect genes.

Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications.

Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.

The Growth and Shape Evolution of Indium Nanoplates Studied by In Situ Liquid Cell TEM.

Understanding the growth mechanisms of nanomaterials is crucial for effectively controlling their morphology which may affect their properties. Here, the growth process of indium nanoplates is studied using in situ liquid cell transmission electron microscopy. Quantitative analysis shows that the growth of indium nanoplate is limited by surface reaction. Besides, the growth process has two stages, which is different from that of other metal nanoplates reported previously. At the first stage, indium particles transform gradually from face-centered cubic to body-centered tetragonal (bct) structure as the seeds grow. At the second stage, the seeds grow faster than at the first stage and form indium triangular nanoplates. Indium triangular nanoplates have a bct structure with {011}-twin, which is found to form through kinetic reactions. In addition, the shape evolution of truncated triangle nanoplate with multiple twin planes is studied. The growth rate of truncated edge changes with the varied number of re-entrant grooves. The present work provides valuable insights into the growth mechanism of metal nanoplates with low-symmetric structure and the role of twin planes in the shape evolution of plate-like metal nanomaterials.

A new dual-thickness semi-transparent beamstop for small-angle X-ray scattering.

An innovative dual-thickness semi-transparent beamstop designed to enhance the performance of small-angle X-ray scattering (SAXS) experiments is introduced. This design integrates two absorbers of differing thicknesses side by side into a single attenuator, known as a beamstop. Instead of completely stopping the direct beam, it attenuates it, allowing the SAXS detector to measure the transmitted beam through the sample. This approach achieves true synchronization in measuring both scattered and transmitted signals and effectively eliminates higher-order harmonic contributions when determining the transmission light intensity through the sample. This facilitates and optimizes signal detection and background subtraction. This contribution details the theoretical basis and practical implementation of this solution at the SAXS station on the 1W2A beamline at the Beijing Synchrotron Radiation Facility. It also anticipates its application at other SAXS stations, including that at the forthcoming High Energy Photon Source, providing an effective solution for high-precision SAXS experiments.

Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression.

The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti-HBc compound-colchicine, an alkaloid compound-that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Gabapentinoids-Related Delirium Adverse Events: A Real-World Study from 2004 to 2022 Based on FAERS.

Purpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium. Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts. Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥65 years old. The delirium and deliria levels were higher in the male group than in the female group. Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.

Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome.

BACKGROUND: Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. METHODS: Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model. RESULTS: 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968-1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses. CONCLUSION: A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

Protocol for in vivo nucleic acid delivery utilizing the rolling microneedle electrode array.

Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids. For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1.

Immune profiling of premalignant lesions in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development. OBJECTIVE: This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps. METHODS: Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes. RESULTS: Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid-derived suppressor cells (MDSCs). CONCLUSION: The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

Chromosome-level genome assembly of the invasive pest Pseudococcus jackbeardsleyi (Hemiptera: Pseudococcidae).

Among over 2,000 species of mealybugs (Hemiptera: Pseudococcidae), only 13 genomes have been published so far, seriously limiting the researches on the phylogeny and adaptive evolution of this group. The continuous publication of mealybug genomes will significantly facilitate our exploration of the biological characteristics, detrimental attributes, and control strategies of the Pseudococcidae family. Jack Beardsley mealybug (Pseudococcus jackbeardsleyi) as one of the hazardous invasive pests, it could cause enormous losses to the fruit and vegetable industries worldwide. Herein, we combined Nanopore long-read, short-read Illumina and Hi-C sequencing, generating a high-quality chromosome-level genome assembly of P. jackbeardsleyi. The genome size was determined to be 334.818 Mb, which was assembled into 5 linkage groups with a N50 of 67.233 Mb. The BUSCO analysis demonstrated the completeness of the genome assembly and annotation are 95.7% and 92.8%, respectively. The developed high-quality genome will serve as an asset for delving into the genetic mechanisms underlying the invasiveness of P. jackbeardsleyi, thereby offering a crucial theoretical foundation for the prevention and management of Pseudococcidae pests.

Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation.

BACKGROUND: Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown. METHODS: Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in LUSC. RESULTS: RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (p = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (p = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman's rank correlation, p < 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT-PCR and Western blot verified the high expression of RNMT in LUSC. CONCLUSION: RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.

SPP1 could be an immunological and prognostic biomarker: From pan-cancer comprehensive analysis to osteosarcoma validation.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.

Nanomaterials for bone metastasis.

Bone metastasis, a prevalent occurrence in primary malignant tumors, is often associated with a grim prognosis. The bone microenvironment comprises various coexisting cell types, working together in a coordinated manner. This dynamic microenvironment plays a pivotal role in the initiation and progression of bone metastases. While cancer therapies have made advancements, the available options for addressing bone metastases remain insufficient. The advent of nanotechnology has ushered in a new era for managing and preventing bone metastases because of the physicochemical and adaptable advantages of nanoplatforms. In this review, we make an introduction of the underlying mechanisms and the current clinical therapies of bone metastases, highlighting the advances of intelligent nanosystems that can stimulate vascular regeneration, promote bone regeneration, eliminate tumor cells, minimize bone damage, and expedite bone healing. The innovation surrounding bone-targeting nanoplatforms presents a fresh approach to the theranostics of bone metastases.

A nomogram to predict intracranial hypertension in moderate traumatic brain injury patients.

OBJECTIVE: Patients with moderate traumatic brain injury (TBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which moderate TBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in moderate TBI patients. METHODS: Baseline data collected on admission of 296 moderate TBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multi-variable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% confidence interval [CI]: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747∼0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing moderate TBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying moderate TBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

A Small-Molecule Inhibitor of Factor Inhibiting HIF Binding to a Tyrosine-Flip Pocket for the Treatment of Obesity.

In animals, limiting oxygen upregulates the hypoxia-inducible factor (HIF) and promotes a metabolic shift towards glycolysis. Factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that regulates HIF function by reducing its interaction with histone acetyl transferases. HIF levels are negatively regulated by the HIF prolyl hydroxylases (PHDs) which, like FIH, are 2-oxoglutarate (2OG) oxygenases. Genetic loss of FIH promotes both glycolysis and aerobic metabolism. FIH has multiple non-HIF substrates making it challenging to connect its biochemistry with physiology. A structure-mechanism guided approach identified a highly potent in vivo active FIH inhibitor, ZG-2291, the binding of which promotes a conformational flip of a catalytically important tyrosine, enabling the selective inhibition of FIH over other Jumonji C subfamily 2OG oxygenases. Consistent with genetic studies, ZG-2291 promotes thermogenesis and ameliorates symptoms of obesity and metabolic dysfunction in ob/ob mice. The results reveal ZG-2291 as a useful probe for the physiological functions of FIH and identify FIH inhibition as a promising strategy for obesity treatment.

ATP-elicited Cation Fluxes Promote Volume-regulated Anion Channel LRRC8/VRAC Transport cGAMP for Antitumor Immunity.

The cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells' cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-ß response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear. In this study, we found that extracellular ATP, an immune regulatory molecule widely present in the tumor microenvironment, can potentiate cGAMP transfer, thereby boosting the STING signaling and IFN-ß response in murine macrophages and fibroblasts. Notably, genetic ablation or chemical inhibition of murine volume-regulation anion channel LRRC8/volume-regulated anion channel (VRAC), a recently identified cGAMP transporter, abolished ATP-potentiated cGAMP transfer and STING-dependent IFN-ß response, revealing a crucial role of LRRC8/VRAC in the cross-talk of extracellular ATP and cGAMP. Mechanistically, ATP activation of the P2X family receptors triggered Ca2+ influx and K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked K+ efflux alleviated the phosphorylation of VRAC's obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated that the phosphorylation of S174 on LRRC8A could act as a checkpoint for VRAC in the steady state and a rheostat of ATP responsiveness. In an MC38-transplanted tumor model, systemically blocking CD39 and ENPP1, hydroxylases of extracellular ATP and cGAMP, respectively, elevated antitumor NK, NKT, and CD8+ T cell responses and restrained tumor growth in mice. Altogether, this study establishes a crucial role of ATP in facilitating LRRC8/VRAC transport cGAMP in the tumor microenvironment and provides new insight into harnessing cGAMP transfer for antitumor immunity.

KTA-OPO for 1742 nm laser generation driven by a composite Nd:YVO4-based self-Raman laser.

In this work, a double-end diffusion bonded Nd:YVO4 self-Raman laser was designed to drive an intracavity, noncritically-phase-matched KTiOAsO4 (KTA) optical parametric oscillator (OPO). Both conversion efficiency and output power at 1.7 µm (the wavelength of the OPO signal field) were improved by effectively reducing the thermal lens effect and increasing the effective length of self-Raman medium. At an incident pump power of 15.4 W, the output power for 1742 nm output laser reached 2.16 W with a conversion efficiency of 14%, and the output having a pulse width of 10.5 ns and a pulse repetition frequency of 90 kHz. The competition between the OPO and cascaded Raman laser was observed when the incident pump power was above 12.4 W. The results highlight that in order to improve output power at 1742 nm, it is critical that both the cascaded, second-Stokes field at 1313 nm and the signal field generated at 1534 nm from the 1064 nm field driving the KTA-OPO be minimized, if not completely suppressed. This laser system combining the processes of stimulated Raman scattering and optical parametric oscillation for the generation of laser emission at 1742 nm may find significant application across a broad range of fields including biological engineering, laser therapy, optical coherence tomography and for the generation of mid-infrared laser wavelengths.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.