Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury.

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

Highly stable mixed-phase Cs-Cu-I films with tunable optoelectronic properties for UVB photodetector applications.

Ultraviolet (UV) photodetector plays an important role in military, civilian and people's daily life, and is an indispensable part of spectral detection. However, photodetectors target at the UVB region (280-320 nm) are rarely reported, and the devices detected by medium-wave UV light generally have problems such as low detection rate, low sensitivity, and poor stability, which are difficult to meet the market application needs. Herein, Cs-Cu-I films with mixed-phase have been prepared by vacuum thermal evaporation. By adjusting the proportion of evaporation sources (CsI and CuI), the optical bandgaps of mixed-phase Cs-Cu-I films can be tuned between 3.7 eV and 4.1 eV. This absorption cut-off edge is exactly at both ends of the UVB band, which indicating its potential application in the field of UVB detection. Finally, the photodetectors based on Cs-Cu-I/n-Si heterojunction are fabricated. The photodetector shows good spectral selectivity for UVB band, and has a photoresponsivity of 22 mA/W, a specific detectivity of 1.83*1011 Jones, an EQE over 8.7% and an on/off ratio above 20.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration.

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Lumboperitoneal shunt and ventriculoperitoneal shunt for chronic hydrocephalus after aneurysmal subarachnoid hemorrhage: a comparison.

Objective: Chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) results in poor neurological outcomes and cognitive deficits. Currently, the main treatments for chronic hydrocephalus include ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS); however, the optimal treatment for chronic hydrocephalus after aSAH remains controversial. Method: The records of 82 patients were retrospectively analyzed, and the patients were divided into VPS and LPS groups based on surgical methods. The efficacy, shunt successful rate and complications were compared. The assessments of treatment efficacy included the Evans index score (EIS), Keifer's hydrocephalus score (KHS), Mini-Mental State Examination (MMSE) score and functional independence measure (FIM). Patients were followed up for three months to observe the postoperative curative effects and complications. Results: The rate of shunt obstruction was significantly higher in the LPS group than that in the VPS group (p < 0.05), and the shunt successful rate was significantly higher in the VPS group than that in the LPS group (p < 0.05). The total rate of complications was 24.4% for LPS and 39% for VPS. The improvements in EIS, KHS, MMSE, and FIM within each group after the shunt were significantly different compared to those before shunt (p < 0.05). Compared to those in the LPS group, the improvements in EIS, KHS, MMSE, and FIM were significantly different in the VPS group after shunt (p < 0.05). Conclusion: Compared with LPS, VPS in the treatment for chronic hydrocephalus after aSAH had greater therapeutic efficacy, as indicated by improved radiological outcomes, improved shunt successful rate, improved clinical outcomes, and improved quality of life. Therefore, we believe that VPS is the preferred treatment option for chronic hydrocephalus after aSAH, while LPS should only be used as an alternative to VPS.

Alterations in gut microbiota and bile acids by proton-pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance.

Several observational studies have suggested that proton-pump inhibitor (PPI) use might increase diabetes risk, but the mechanism remains unclear. This study aimed to investigate the effects of PPI use on gut microbiota and bile acids (BAs) profiles, and to explore whether these changes could mediate the association of PPIs use with fasting blood glucose (FBG) levels and insulin resistance (IR) in Chinese population. A cross-sectional study was conducted in Shenzhen, China, from April to August 2021, enrolled 200 eligible patients from the local hospital. Participants completed a questionnaire and provided blood and stool samples. Gut microbiome was measured by16S rRNA gene sequencing, and bile acids were quantified by UPLC-MS/MS. Insulin resistance (IR) was assessed using the Homeostasis Model Assessment 2 (HOMA2-IR). PPI use was positively associated with higher levels of FBG and HOMA2-IR after controlling for possible confounders. PPI users exhibited a decreased Firmicutes and an increase in Bacteroidetes phylum, alongside higher levels of glycoursodeoxycholic acid (GUDCA) and taurochenodeoxycholic acid (TCDCA). Higher abundances of Bacteroidetes and Fusobacterium as well as higher levels of TCDCA in PPI users were positively associated with elevated FBG or HOMA2-IR. Mediation analyses indicated that the elevated levels of FBG and HOMA2-IR with PPI use were partially mediated by the alterations in gut microbiota and specific BAs (i.e., Fusobacterium genera and TCDCA). Long-term PPI use may increase FBG and HOMA2-IR levels, and alterations in gut microbiota and BAs profiles may partially explain this association.

Associations of maternal and personal smoking with all-cause and cause-specific mortality risk and life expectancy: a prospective cohort study.

OBJECTIVES: The aim of this study was to evaluate the individual and combined effects of maternal smoking during pregnancy (MSDP) and personal smoking on mortality and life expectancy. STUDY DESIGN: A prospective cohort study based on the UK Biobank, with a median follow-up of 12.47 years. METHODS: This study employed multivariate Cox regression to determine the relative risks of mortality from all causes and specific diseases according to maternal and/or personal smoking status and pack-years of smoking (0, 1-20, 21-30, >30). Additionally, this study estimated the additive interaction between the two exposures. Life table analyses were performed using the estimated age-specific mortality rates to forecast life expectancy. RESULTS: Results indicated that MSDP elevated the risk of all-cause mortality (HR = 1.12, 95% CI: 1.09-1.15) and mortality due to neoplasms (HR = 1.10, 95% CI: 1.06-1.12), circulatory (HR = 1.13, 95% CI: 1.06-1.19), respiratory (HR = 1.27, 95% CI: 1.16-1.40) and digestive system diseases (HR = 1.22, 95% CI: 1.08-1.38). Notably, both multiplicative and additive interactions were observed between maternal and personal smoking, with Relative Excess Risk due to Interaction (RERI) values for mortality from all causes, neoplasms, circulatory, and respiratory diseases being 0.21, 0.22, 0.16, and 0.76, respectively. This study also found a trend towards shorter gained life expectancy when maternal smoking and increasing pack-years of personal smoking were combined. CONCLUSIONS: In this cohort study of UK Biobank, MSDP was associated with an increased risk of all-cause mortality and reduced life expectancy, suggesting that quitting smoking during pregnancy might have health and longevity benefits for both generations.

Effects of ocean acidification and polystyrene microplastics on the oysters Crassostrea gigas: An integrated biomarker and metabolomic approach.

The adverse impacts of microplastics (MPs) or ocean acidification (OA) on mollusks have been widely reported, however, little is known about their combined effects on mollusks. The oysters Crassostrea gigas were exposed to two sizes of polystyrene MPs with 1 × 104 particles/L (small polystyrene MPs (SPS-MPs): 6 µm, large polystyrene MPs (LPS-MPs): 50-60 µm) at two pH levels (7.7 and 8.1) for 14 days. The antagonistic effects between MPs and OA on oysters were mainly observed. Single SPS-MPs exposure can induce CAT enzyme activity and LPO level in gills, while LPS-MPs exposure alone can increase PGK and PEPCK gene expression in digestive glands. Ocean acidification can increase clearance rate and inhibit antioxidant enzyme activity, whereas combined exposure of OA and SPS-MPs can affect the metabolomic profile of digestive glands. This study emphasized that the potential toxic effects of MPs under the scene of climate change should be concerned.

Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

Chromosome-level genome of Thymus mandschuricus reveals molecular mechanism of aroma compounds biosynthesis.

Background: Thymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics. Results: We utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression. Conclusion: This study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

TMEM119 (c.G143A, p.S48L) Mutation Is Involved in Primary Failure of Eruption by Attenuating Glycolysis-Mediated Osteogenesis.

Primary failure of eruption (PFE) is a rare oral disease with an incidence rate of 0.06%. It is characterized by abnormal eruption mechanisms that disrupt tooth eruption. The underlying pathogenic genetic variant and mechanism of PFE remain largely unknown. The purpose of this study was to explore the role of a novel transmembrane protein 119 (TMEM119) mutation in two PFE patients in a Chinese family. Information collection was performed on the family with a diagnosis of PFE, and blood samples from patients and healthy family members were extracted. Whole-exome sequencing was performed. Bioinformatics analysis revealed that a heterozygous variant in the TMEM119 gene (c.G143A, p.S48L) was a disease-associated mutation in this family. Recombinant pcDNA3.1 plasmid-containing wild-type and mutant TMEM119 expression cassettes were successfully constructed and transfected into MC3T3-E1 cells, respectively. The results of in vitro analysis suggested that the subcellular distribution of the TMEM119 protein was transferred from the cell cytoplasm to the nucleus, and the ability of cells to proliferate and migrate as well as glycolytic and mineralized capacities were reduced after mutation. Furthermore, rescue assays showed that activating transcription factor 4 (ATF4) overexpression rescued the attenuated glycolysis and mineralization ability of cells. Results of in vivo analysis demonstrated that TMEM119 was mainly expressed in the alveolar bone around the mouse molar germs, and the expression level increased with tooth eruption, demonstrated using immunohistochemistry and immunofluorescence. Collectively, the novel TMEM119 mutation is potentially pathogenic in the PFE family by affecting the glucose metabolism and mineralized function of osteoblasts, including interaction with ATF4. Our findings broaden the gene mutation spectrum of PFE and further elucidate the pathogenic mechanism of PFE.

Dexmedetomidine versus midazolam as intranasal premedication for intravenous deep sedation in pediatric dental treatment.

Background/purpose: Optimal sedation management for pediatric dental treatment demands special focus as it's tubeless and shares a same oral space. The study was to evaluate dexmedetomidine compared to midazolam for intranasal premedication in pediatric dental treatment under intravenous deep sedation. Materials and methods: A hundred children aged 3-7 years scheduled for elective dental treatment under intravenous deep sedation anesthesia were enrolled, of whom 50 children (Group D) were intranasally premedicated with 2.0 µg/kg dexmedetomidine and the remaining 50 children (Group M) received traditional 0.2 mg/kg midazolam. Acceptance rate of venipuncture was regarded as the primary endpoint. Results: The acceptance rate of venipuncture in Group D and Group M were 76% versus 52%, respectively (P = 0.021). More children in Group M complained about bitter/sour taste than Group D (62% vs. 8%, P < 0.001). Intraoperatively, children in Group M were found to have more choking cough than Group D (30% vs. 9%, P = 0.003), and patients in Group M required more suction (18 [36%] in Group M vs. 4 [8%] in Group D, P = 0.001). There were no significant differences between the groups in the incidences of temporal hypoxemia (SpO2 ≤ 90%), however, two children in Group M experienced hypoxemia over 10 s. Conclusion: Compared to the 0.2 mg/kg midazolam, children premedicated with 2.0 µg/kg intranasal dexmedetomidine showed superior venipuncture acceptance, had less intraoperative choking cough and required fewer suction. It seems to be a good alternative to midazolam as premedication for deep sedation in pediatric dental treatment.

Weakly supervised image segmentation beyond tight bounding box annotations.

Weakly supervised image segmentation approaches in the literature usually achieve high segmentation performance using tight bounding box supervision and decrease the performance greatly when supervised by loose bounding boxes. However, compared with loose bounding box, it is much more difficult to acquire tight bounding box due to its strict requirements on the precise locations of the four sides of the box. To resolve this issue, this study investigates whether it is possible to maintain good segmentation performance when loose bounding boxes are used as supervision. For this purpose, this work extends our previous parallel transformation based multiple instance learning (MIL) for tight bounding box supervision by integrating an MIL strategy based on polar transformation to assist image segmentation. The proposed polar transformation based MIL formulation works for both tight and loose bounding boxes, in which a positive bag is defined as pixels in a polar line of a bounding box with one endpoint located inside the object enclosed by the box and the other endpoint located at one of the four sides of the box. Moreover, a weighted smooth maximum approximation is introduced to incorporate the observation that pixels closer to the origin of the polar transformation are more likely to belong to the object in the box. The proposed approach was evaluated on two public datasets using dice coefficient when bounding boxes at different precision levels were considered in the experiments. The results demonstrate that the proposed approach achieves state-of-the-art performance for bounding boxes at all precision levels and is robust to mild and moderate errors in the loose bounding box annotations. The codes are available at https://github.com/wangjuan313/wsis-beyond-tightBB.

The short-term impact of comprehensive caries treatment on the supragingival microbiome of severe early childhood caries.

BACKGROUND: Children affected by severe early childhood caries (S-ECC) usually need comprehensive caries treatment due to the extensive of caries. How the oral microbiome changes after caries therapy within the short-term warrant further study. AIM: This study aimed to investigate the short-term impact of comprehensive caries treatment on the supragingival plaque microbiome of S-ECC children. DESIGN: Thirty-three children aged 2-4 years with severe caries (dt > 7) were recruited. Comprehensive caries treatment was performed under general anesthesia in one session and included restoration, pulp treatment, extraction, and fluoride application. Supragingival plaque was sampled pre- and 1-month posttreatment. The genomic DNA of the supragingival plaque was extracted, and bacterial 16S ribosomal RNA gene sequencing was performed. RESULTS: Our data showed that the microbial community evenness significantly decreased posttreatment. Furthermore, comprehensive caries treatment led to more diverse microbial structures among the subjects. The interbacterial interactions reflected by the microbial community's co-occurrence network tended to be less complex posttreatment. Caries treatment increased the relative abundance of Corynebacterium matruchotii, Corynebacterium durum, Actinomyces naeslundii, and Saccharibacteria HMT-347, as well as Aggregatibacter HMT-458 and Haemophilus influenzae. Meanwhile, the relative abundance of Streptococcus mutans, three species from Leptotrichia, Neisseria bacilliformis, and Provotella pallens significantly decreased posttreatment. CONCLUSION: Our results suggested that comprehensive caries treatment may contribute to the reconstruction of a healthier supragingival microbiome.

The ergodicity question when imaging DNA conformation using liquid cell electron microscopy.

Assessing the ergodicity of graphene liquid cell electron microscope measurements, we report that loop states of circular DNA interconvert reversibly and that loop numbers follow the Boltzmann distribution expected for this molecule in bulk solution, provided that the electron dose is low (80-keV electron energy and electron dose rate 1-20 e- Å-2 s-1). This imaging technique appears to act as a "slow motion" camera that reveals equilibrated distributions by imaging the time average of a few molecules without the need to image a spatial ensemble.

Regular use of paracetamol and risk of liver cancer: a prospective cohort study.

BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. CONCLUSION: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

Knockdown of the ABCG23 Gene Disrupts the Development and Lipid Accumulation of Panonychus citri (Acari/Tetranychidae).

Panonychus citri is a worldwide citrus pest that is currently controlled through the use of insecticides. However, alternative strategies are required to manage P. citri. Recent studies suggest that the ATP-binding cassette (ABC) transporter G subfamily plays a crucial role in transporting cuticular lipids, which are essential for the insect's barrier function against microbial penetration. Therefore, investigating the potential of the ABC transporter G subfamily as a control measure for P. citri could be a promising approach. Based on the genome database, the gene was cloned, and the transcriptional response of ABCG23 for the different developmental stages of P. citri and under spirobudiclofen stress was investigated. Our results showed that the expression level of ABCG23 was significantly lower in adult females exposed to treatment compared to the control and was higher in females than males. The knockdown of ABCG23 using RNAi led to a decrease in the survival rate, fecundity, and TG contents of P. citri. Additionally, a lethal phenotype was characterized by body wrinkling and darkening. These results indicate that ABCG23 may be involved in cuticular lipid transportation and have adverse effects on the development and reproduction of P. citri, providing insight into the discovery of new targets for pest management based on the insect cuticle's penetration barrier function.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study.

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Fatty Acid Elongase Gene PcELO7 is Essential for Lipid Accumulation and Fecundity of Panonychus citri (Acari: Tetranychidae).

RNA interference (RNAi) has been proposed as a promising strategy for sustainable and ecofriendly pest control. The insect cuticle lipids were deposited on the body surface and functioned as a defense against chemical xenobiotics. They consisted of aliphatic compounds, including free fatty acids (FFAs). However, elongase of very long chain fatty acids (ELOs) is essential for FFA biosynthesis; the function of ELO is still unknown in many arthropods, including Panonychus citri (P. citri). In this study, three ELOs were cloned. Developmental-specific mRNA expression results revealed that three PcELOs were highly expressed in egg and adult females. Whereas PcELO7 was dominantly expressed in adult females. Under spirobudiclofen stress, ELOs mRNA expression had different changes, and PcELO7 was down-regulated. The silencing of PcELO7 resulted in a dramatic reduction of oviposition and hatchability. Significant reduction of FFA contents was also examined within PcELO7-repressed P. citri. In addition, we found that PcELO7 mRNA levels were related to fecundity and could affect triacylglycerol (TG) contents. The findings demonstrated that the introduction of dsPcELO7 via oral feeding induced the RNA interference-mediated silencing of a special target gene and could result in mortality and reproduction. In conclusion, PcELO7 is a special RNAi target for P. citri control, and its lethal mechanism might be disturbing lipids biosynthesis.

Dermal papilla cell-secreted biglycan regulates hair follicle phase transit and regeneration by activating Wnt/ß-catenin.

Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/ß-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/ß-catenin signalling pathway and could be a potential treatment target for hair loss diseases.

Physiological and transcriptomic analysis reveals the toxic and protective mechanisms of marine microalga Chlorella pyrenoidosa in response to TiO2 nanoparticles and UV-B radiation.

Concerns have been raised regarding the adverse effects of nanoparticles (NPs) on marine organisms, as an increasing number of NPs inevitably enter the marine environment with the development of nanotechnology. Owing to the photocatalytic properties, TiO2 NPs' toxicity may be aggravated by enhanced UV-B resulting from stratospheric ozone depletion. However, the molecular mechanisms of phytoplankton in response to TiO2 NPs under UV-B remains poorly understood. In this study, we integrated whole transcriptome analysis with physiological data to provide understanding on the toxic and protective mechanisms of marine Chlorella pyrenoidosa in response to TiO2 NPs under UV-B. The results indicated that the changes in gene expression could be related to the growth inhibition and TiO2 NP internalization in C. pyrenoidosa, and several molecular mechanisms were identified as toxicity response to TiO2 NPs and UV-B. Differential expression of genes involved in glycerophospholipids metabolism indicated that cell membrane disruption allowed TiO2 NPs to enter the algal cell under UV-B exposure, although the up-regulation of genes involved in the general secretory dependent pathway and the ATP-binding cassette transporter family drove cellular secretion of extracellular polymeric substances, acting as a barrier that prevent TiO2 NP internalization. The absence of changes in gene expression related to the antioxidant system may be responsible for the severe oxidative stress observed in algal cells following exposure to TiO2 NPs under UV-B irradiation. Moreover, differential expression of genes involved in pathways such as photosynthesis and energy metabolism were up-regulated, including the light-harvesting, photosynthetic electron transport coupled to photophosphorylation, carbon fixation, glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that more energy and metabolites were supplied to cope with the toxicity of TiO2 NPs and UV-B. The obtained results provide valuable information on the molecular mechanisms of response of marine phytoplankton exposed to TiO2 NPs and UV-B.