Newborn screening for G6PD deficiency in HeFei, FuYang and AnQing, China: Prevalence, cut-off value, variant spectrum.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive Mendelian genetic disorder characterized by neonatal jaundice and hemolytic anemia, affecting more than 400 million people worldwide. The purpose of this research was to investigate prevalence rates of G6PD deficiency and to evaluate and establish specific cut-off values in early prediction of G6PD deficiency by regions (HeFei, FuYang, AnQing) on different seasons, as well as to investigate the frequencies of G6PD gene mutations among three regions mentioned above. Methods: A total of 31,482 neonates (21,402, 7680, and 2340 for HeFei, FuYang, and AnQing cities, respectively) were recruited. Positive subjects were recalled to attend genetic tests for diagnosis. G6PD activity on the Genetic screening processor (GSP analyzer, 2021-0010) was measured following the manufacturerzs protocol. The cut-off value was first set to 35 U/dL. The receiver operating characteristics (ROC) curve was employed to assess and compare the efficiency in predicting G6PD deficiency among HeFei, FuYang, and AnQing cities in different seasons.

Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer.

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer. However, knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited. Here, by taking advantage of in situ Hi-C, RNA-sequencing, and chromatin immunoprecipitation sequencing (ChIP-seq), we investigated structural reorganization and functional changes in chromosomal compartments, topologically associated domains (TADs), and CCCTC binding factor (CTCF)-mediated loops in gallbladder cancer (GBC) tissues and cell lines. We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes. Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls. Furthermore, the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial-mesenchymal transition activation were enriched in cancer compared with their control counterparts. Cancer-specific enhancer-promoter loops, which contain multiple transcription factor binding motifs, acted as a central element to regulate aberrant gene expression. Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions. Collectively, our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

Biomimetic, knittable aerogel fiber for thermal insulation textile.

Aerogels have been considered as an ideal material for thermal insulation. Unfortunately, their application in textiles is greatly limited by their fragility and poor processability. We overcame these issues by encapsulating the aerogel fiber with a stretchable layer, mimicking the core-shell structure of polar bear hair. Despite its high internal porosity over 90%, our fiber is stretchable up to 1000% strain, which is greatly improved compared with that of traditional aerogel fibers (~2% strain). In addition to its washability and dyeability, our fiber is mechanically robust, retaining its stable thermal insulation property after 10,000 stretching cycles (100% strain). A sweater knitted with our fiber was only one-fifth as thick as down, with similar performance. Our strategy for this fiber provides rich possibilities for developing multifunctional aerogel fibers and textiles.

Preferential ice growth on grooved surface for crisscross-aligned graphene aerogel with large negative Poisson's ratio.

Ice formation on solid surfaces is a ubiquitous process in our daily life, and ice orientation plays a critical role in anti-icing/deicing, organ cryo-preservation, and material fabrication. Although previous studies have shown that surface grooves can regulate the orientation of ice crystals, whether the parallel or perpendicular alignment to the grooves is still under debate. Here, we systematically investigate ice formation and its oriented growth on grooved surfaces through both in situ observation and theoretical simulation, and discover a remarkable size effect of the grooves. With the designability of surface groove patterns, the preferential growth of ice crystals is programmed for the fabrication of a crisscross-aligned graphene aerogel with large negative Poisson's ratio. In addition, the size effect provides guidance for the design and fabrication of solid surfaces where the effective control of ice orientation is highly desired, such as efficient deicing, long time organ cryo-preservation, and ice-templated materials.

Rapidly detecting the carcinogen acetaldehyde: preparation and application of a flower-like MoS2 cataluminescence sensor at low working temperature.

In this paper, a cataluminescence (CTL) gas sensor based on flower-like molybdenum disulfide (MoS2) is developed. The experimental results show that it has high sensitivity and selectivity to acetaldehyde. The CTL sensor has the advantage of fast response; the response time is about 3 s and the recovery time is about 40 s. The optimal working temperature of this sensor is 174 °C, which is lower than that of the CTL sensors used for acetaldehyde detection in many other reports. Under the optimized conditions, the CTL signal intensity shows a good linear relationship with acetaldehyde concentration (R2 = 0.9991) within the concentration range of 40-2000 ppm, and the detection limit (LOD) is 3.75 ppm. The selectivity experiment results show that the sensor has an obvious response to acetaldehyde and a very weak response to acetic acid, and has no response to many other VOCs (ether, cyclohexane, butyl ether, carbon tetrachloride, ethanol, toluene, formaldehyde, glycerol, trichloromethane and xylene). After 8 repeated measurements for four weeks, the relative standard deviation (RSD) of the CTL sensor is 1.03%, indicating that it has good reproducibility and stability, which shows that the CTL sensor has a promising prospect for the detection of acetaldehyde.

Prenatal environmental adversity and child neurodevelopmental delay: the role of maternal low-grade systemic inflammation and maternal anti-inflammatory diet.

Maternal inflammation has been proposed as a possible pathway connecting prenatal environmental adversity (PEA), which includes maternal overweightness or obesity, diabetes, hypertensive disorders, and mood or anxiety disorders, to child neurodevelopmental delay. However, effective preventive measures have not yet been reported. Herein, we aimed to investigate whether a maternal anti-inflammatory diet reduced the risk of PEA-induced neurodevelopmental delay, by inhibiting inflammation. This prospective study included 7438 mother-child pairs. Maternal overweightness or obesity, diabetes, and hypertensive disorders were diagnosed before 28 week gestation. Maternal depression disorders were identified using the Edinburgh postnatal depression survey (EPDS) during mid-pregnancy. During mid- and late pregnancy, maternal high-sensitivity C-reactive protein (hs-CRP) levels were measured to evaluate systemic inflammation. The inflammatory potential of the diet was evaluated using the food-based empirical dietary inflammatory pattern (EDIP) score during mid-pregnancy. Pregnant women were classified into high- or low-score groups based on the median EDIP score. The outcomes of neurodevelopmental delay at 6-36 month postpartum were extracted from the Register of Child Healthcare. Among the 7438 mother-child pairs, 2937 (39.5%) were exposed to PEA, and neurodevelopmental delay occurred in 540 (7.3%). Children exposed to PEA had a higher risk of neurodevelopmental delay than those not exposed. PEA exposure was associated with increased hs-CRP during pregnancy in a PEA monotonic manner, an interquartile range increase in hs-CRP in mid- and late pregnancy was associated with an increased risk of child neurodevelopmental delay. Higher maternal persistent inflammation partially mediated the effect of PEA exposure on child neurodevelopmental delay by 17.19%. An increased risk of PEA-related neurodevelopmental delay was observed only in the children of mothers with high-EDIP rather than low-EDIP. These results suggest that increased systemic inflammation through mid- and late pregnancy mediates the association between PEA and child neurodevelopmental delay. A maternal anti-inflammatory diet may improve PEA-induced neurodevelopmental delay, by inhibiting inflammation.

Association of Gestational Diabetes Mellitus Complicated With Short Sleep Duration and Child Neurodevelopmental Delay.

CONTEXT: Gestational diabetes mellitus (GDM) is a risk factor for child neurodevelopmental delay. Maternal short sleep duration (SSD) may aggravate glucose metabolism disorder in women with GDM. However, it is unclear whether maternal SSD will further affect the neurodevelopmental outcomes of children. OBJECTIVE: To identify the association of GDM complicated with SSD and child neurodevelopmental delay. METHODS: This prospective study included 7069 mother-child pairs. Between 24 and 28 weeks of gestation, GDM was based on the 75-g oral-glucose-tolerance test. Self-reported sleep duration was collected via the Pittsburgh Sleep Quality Index questionnaire in the second (24-28 weeks) and third (32-36 weeks) trimesters. Outcomes of neurodevelopmental delay in 6 to 36 months postpartum were evaluated using Denver Developmental Screening Test-II and Gesell Development Diagnosis Scale. RESULTS: Compared with the unexposed group, women with "GDM + SSD" have the greatest risks of child neurodevelopmental delay (hazard ratio with 95% CI: 1.58 [1.03-2.44]). "GDM + SSD" was associated with the greatest risks of maternal-fetal glucose metabolic disorder. An interquartile ratio (0.58 mmol/L) increase in cord blood C-peptide was associated with the risk of child neurodevelopmental delay (hazard ratio with 95% CI: 1.28 [1.12-1.48]). The stronger linear association of maternal glucose metabolism profiles and C-peptide in women with "GDM + SSD" was also demonstrated. The proportion of association between "GDM + SSD" and child neurodevelopmental delay mediated by C-peptide was 14.4%. CONCLUSION: GDM complicated with SSD was associated with increased risk for child neurodevelopmental delay by enhancing the intergenerational association of maternal-fetal glucose metabolism disorder.

Phyllosphere bacterial strains Rhizobium b1 and Bacillus subtilis b2 control tomato leaf diseases caused by Pseudomonas syringae pv. tomato and Alternaria solani.

AIMS: Show that tomato leaf phyllosphere bacteria are candidates for biocontrol of tomato leaf diseases. METHODS AND RESULTS: Seven bacterial isolates from surface-sterilized Moneymaker tomato plants were tested for growth inhibition of 14 tomato pathogens on potato dextrose agar. Biocontrol assays were conducted with tomato leaf pathogens, Pseudomonas syringae pv. tomato (Pto) and Alternaria solani (A. solani). Two potential isolates showing the greatest inhibition were identified by 16S rDNA sequencing as Rhizobium sp. (isolate b1) and Bacillus subtilis (isolate b2), both produce protease and isolate b2 cellulase. Both reduced tomato leaf infections by Pto and A. solani in detached leaf bioassays. Both bacteria b1 and b2 reduced pathogen development in a tomato growth trial. Bacteria b2 also induced the tomato plant salicylic acid (SA) immune response pathway. Disease suppression in biocontrol assays with b1 and b2 varied between five commercial tomato varieties. CONCLUSIONS: Tomato phyllosphere bacteria when used as phyllosphere inoculants, inhibited tomato diseases caused by Pto and A. solani.

Successful conversion surgery for locally advanced gallbladder cancer after gemcitabine and nab-paclitaxel chemotherapy.

Objective: Gallbladder cancer (GBC) is highly malignant and is often diagnosed at the advanced stage. Lack of opportunity to surgery results in an unsatisfactory outcome. This pilot study employed gemcitabine combined with nab-paclitaxel (AG) as a conversion therapeutic measure for locally advanced GBC and successfully achieved conversion surgery in three initially unresectable GBC patients. We will introduce our experience on improving the outcome of this dismal disease. Methods: Radiology and nuclear medicine imaging were performed in each patient, and resectability was evaluated by joint consultation of our multi-disciplinary team (MDT). Patients evaluated as unresectable were treated with the AG regimen and re-evaluated for treatment response. When complete or partial response is achieved, MDT opinion would be required to assess the possibility of performing conversion surgery with R0 resection. Results: Three GBC patients who were initially evaluated as unresectable successfully underwent R0 resection after conversion therapy with the AG regimen. The first case was a recurrent GBC patient evaluated as locally advanced and eventually achieved pathological complete response. The second case was a GBC patient who underwent R1 resection with residual lesions in the gallbladder bed and isolated No. 16 lymph node metastasis and who had a pathologically complete response after treatment. The third case had multiple but resectable liver metastases; both objective response and partial pathologic response were achieved. None of the patients experienced serious treatment-related adverse events. All cases revealed no evidence of recurrence or metastasis after a median follow-up of 12 months. Conclusions: Conversion therapy shows a favorable efficacy in those unresectable GBC patients. Gemcitabine plus nab-paclitaxel has the potential to be used as a preoperative treatment option for GBC patients at the advanced stage. To further explore the efficacy of AG on conversion therapy for GBC patients, a prospective clinical trial has been registered (ChiCTR2200055698).

LncRNA MNX1-AS1 sustains inactivation of Hippo pathway through a positive feedback loop with USP16/IGF2BP3 axis in gallbladder cancer.

The long non-coding RNAs (lncRNAs) have been implicated in multiple human cancers, which may offer great potential as putative targets for cancer diagnosis and treatment. However, the roles of most lncRNAs in gallbladder cancer (GBC) remain poorly understood. The objective of this research involves investigating the clinical implications and underlying mechanism of lncRNA motor neuron and pancreas homeobo×1 antisense RNA 1 (MNX1-AS1) in GBC. This study shows that MNX1-AS1 expression is elevated in the tissues of GBC patients, and is strongly associated with reduced patient survival. Functionally, MNX1-AS1 significantly stimulates the proliferation and metastasis of GBC cells in vitro and in vivo. Mechanistically, MNX1-AS1 is transcriptionally activated by TEA domain family member 4 (TEAD4), and suppresses insulin-like growing factor 2 mRNA-binding protein 3 (IGF2BP3) degradation by recruiting ubiquitin specific peptidase 16 (USP16). Furthermore, MNX1-AS1/IGF2BP3 axis inhibits the Hippo signaling pathway and subsequently activates TEAD4, thereby forming a positive feedback loop. According to our results, MNX1-AS1 facilitates tumorigenesis, progression and metastasis of GBC through a MNX1-AS1/IGF2BP3/Hippo pathway positive feedback loop, which could be both diagnostically and therapeutically helpful in GBC.

Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway.

PURPOSE: This study aimed to investigate the efficiency of our chemically synthesized TT-00420, a novel spectrum-selective multiple protein kinase inhibitor, in cultured cells and animal models of gallbladder cancer (GBC) and explore its potential mechanism. METHODS: Multiple GBC models were established to assess the anti-tumor efficiency, toxicity, and pharmacokinetics of TT-00420. Integrated transcriptomic, proteomic and phosphoproteomic analysis was conducted to identify potential downstream effectors of TT-00420. Western blotting, qRT-PCR, nuclear-cytoplasm separation, and immunofluorescence were performed to confirm the multi-omic results and explore the molecular mechanism of TT-00420. Immunohistochemistry was used to detect FGFR1 and p-FGFR1 expression levels in GBC samples. Autodock software was utilized to investigate the potential binding mode between the TT-00420 and the human FGFR1. RESULTS: We found that TT-00420 exerted potent growth inhibition of GBC cell lines and multiple xenograft models. Treatment of mice with 15 mg/kg TT-00420 via gavage displayed a half-life of 1.8 h in the blood and rapid distribution to the liver, kidneys, lungs, spleen, and tumors at 0.25 h, but no toxicity to these organs over 2 weeks. Multi-omic analysis revealed c-Jun as a potential downstream effector after TT-00420 treatment. Mechanistically, TT-00420 showed rigorous ability to block FGFR1 and its downstream JNK-JUN (S63/S73) signaling pathway, and induce c-Jun S243-dependent MEK/ERK reactivation, leading to FASLG-dependent tumor cell death. Finally, we found that FGFR1 and p-FGFR1 expression was elevated in GBC patients and these levels correlated with decreased patient survival. CONCLUSIONS: TT-00420 shows potent antitumor efficacy and may serve as a novel agent to improve GBC prognosis.

Associations of Maternal Adverse Childhood Experiences with Behavioral Problems in Preschool Children.

Investigations have found maternal adverse childhood experiences (ACEs) cause an intergenerational danger to their children's health. However, no study has investigated the effects of maternal ACEs on behavioral problems of preschool children in China and gender differences on these effects. This paper aims to investigate the role of maternal ACEs on behavioral problems of preschool children in China and explore gender differences as related to these behavioral problems. Stratified cluster sampling method was used to select 7318 preschool children from 12 districts in Hefei city, China. A questionnaire survey was conducted to collect information on maternal exposure to ACEs and Conners' Parent Rating Scales. Logistic regression was used to analyze the relationship between maternal ACEs and children's behavioral problems. The prevalence of behavioral problems in preschool children was 16.0%, while it was higher among girls (18.4%) than boys (13.92%) (χ2 = 27.979, p < 0.001). The rate of behavioral problems in children in the group of mothers with ACEs was higher than those without ACEs (all p < 0.05). Maternal ACEs were associated with increased risk of the behavior problems in preschool children (adjusted OR 2.91, 95% CI 2.45-3.45), and no gender difference (in girls 3.01, 2.38-3.81, in boys 2.79, 2.17-3.58, respectively) was found. Maternal ACEs were associated with increased risk of each type of the behavioral problems of preschool children, except that maternal emotional neglect was not associated with psycho-physical problems, impulse-activities, and anxiety. The only gender differences found were higher conduct problems related to maternal emotional abuse and ACEs and higher anxiety related to maternal physical abuse and community violence in girls compared with boys. Mothers exposured to ACEs are more likely to have children with behavioral health problems in preschool period. Further research is needed to explore the mechanisms by which maternal ACEs influence children's behavioral problems.

Associations of cord blood meta-inflammation and vitamin D with neurodevelopmental delay: A prospective birth cohort study in China.

Aim: To estimate the associations of cord meta-inflammatory markers with neurodevelopment, including the potential impact of cord blood vitamin D levels. Method: The prospective cohort study comprised 7198 participants based on the Maternal & Infants Health in Hefei study. Cord blood C-peptide, high-sensitive C-reactive protein (hsCRP), high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglycerides and 25(OH)D levels were measured. The Gesell Developmental Schedules were used to assess neurodevelopmental outcomes in offspring. Results: After adjusting potential confounders, per quartile increase in cord blood 25(OH)D concentrations was associated with a decreased risk of neurodevelopmental delay [hazard ratios (HR) 0.65 (95% CI 0.57, 0.74)]. Conversely, significant positive associations with cord blood serum C-peptide levels above the 90th percentile [HR 2.38 (95% CI 1.81, 3.13)] and higher levels of cord hsCRP (per quartile increase) [HR 1.18 (95% CI 1.01, 1.37)] with neurodevelopmental delay were observed. These associations could vary by quartiles of cord blood 25(OH)D levels: the adjusted HRs in neurodevelopmental delay comparing children with vs without hyperinsulinemia were 1.28 (95% CI: 1.03, 1.59) for quartiles 1 (lowest), and 1.06 (95% CI: 0.78, 1.44) for quartile 4 (highest). Conclusions: Immune activation and metabolic abnormalities in fetal circulation were associated with neurodevelopmental delay in offspring, which could be attenuated by higher cord blood 25(OH)D levels in a dose-response manner.

Socioeconomic disparities and infancy growth trajectory: a population-based and longitudinal study.

BACKGROUND: The association of low socioeconomic status (SES) with childhood and adolescent obesity has been reported. It is unknown whether low SES affects body mass index (BMI) growth trajectory in the first 12 mo of life. Moreover, accelerated growth as a compensatory mechanism for low birth weight (LBW) during infancy, is an important predictor of later obesity. The aim of the present study was to examine the association of low SES with infancy BMI growth rate and trajectory for LBW and normal birth weight (NBW) infants. METHODS: From September 2012 to October 2014, a total of 387 infants in this longitudinal study was subjected to repeated measures of weight and length from birth to 12 mo in Hefei. Generalized growth mixture modeling was used to classify the infancy BMI growth trajectories. Differences in infancy BMI z score (zBMI) and BMI growth rate between low SES and high SES were estimated based on linear regression after adjusting for several confounders including maternal age, pregnancy BMI, physical activity during pregnancy, paternal BMI as well as alcohol use, paternal smoking status, breastfeeding duration and delivery mode. RESULTS: Infancy BMI trajectories in this study were classified into three categories: rapid growth (class 1), normal growth (class 2) and slow growth (class 3). Low SES infants had the higher zBMI than high SES infants for LBW group at age 6 mo [zBMI difference with 95% CI at 6 mo: 0.28(0.03, 0.53); at 12 mo: 0.21(0.01, 0.43)]. Low SES infants had more rapid zBMI growth rate than those with high SES for low birth weight between 0 and 6 months. Controlling for the confounders, these associations remained robust. We found the lower SES in the rapid growth group. CONCLUSIONS: These findings highlighted the impact of low SES on increasing BMI and accelerated growth during early infancy. Health care and relatively optimal family environment in the first 12 mo of life, especially for LBW infants, are benefit to shape the better infancy growth trajectory.

Anisotropic porous ceramic material with hierarchical architecture for thermal insulation.

Porous ceramic materials are attractive candidates for thermal insulation. However, effective ways to develop porous ceramics with high mechanical and thermal insulation performances are still lacking. Herein, an anisotropic porous silica ceramic with hierarchical architecture, i.e. long-range aligned lamellar layers composed of hollow silica spheres, was fabricated applying a facile bidirectional freezing method. Due to such anisotropic structure, the as-prepared porous silica ceramic displays low thermal conductivity across the layers and high compressive strength along the layers. Additionally, the anisotropic porous silica ceramic is fire-resistant. As a proof of concept, a mini-house was roofed with the anisotropic porous silica ceramic, showing that the indoor temperature could be stabilized against environmental temperature change, making this porous ceramic a promising candidate for energy efficient buildings and other industrial applications. Our study highlights the possibility of combining intrinsically exclusive properties in engineering materials through constructing biomimetic porous structures.

Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer.

BACKGROUND & AIMS: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression. METHODS: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations. RESULTS: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC. CONCLUSIONS: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy. LAY SUMMARY: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.

Transdermal Delivery of Adipocyte Phospholipase A2 siRNA using Microneedles to Treat Thyroid Associated Ophthalmopathy-Related Proptosis.

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease occurring in patients with thyroid disease. Patients with TAO-related proptosis is largely due to excessive orbital adipose tissue Adipocyte phospholipase A2 (AdPLA) is one of the most important regulatory factors in adipocyte lipolysis, which may be associated with TAO-related proptosis. Thus, silencing AdPLA by RNA interference may be beneficial for the treatment of TAO. In this study, we sought to evaluate the efficiency of two types of microneedles to deliver siRNAs for silencing AdPLA. Our results showed that AdPLA mRNA was up-regulated in the orbit adipose tissues from TAO patients. Silence of AdPLA by siRNA can reduce lipid accumulation in both human and mouse adipocyte cell lines. Moreover, silence effects of silicon microneedle array patch-based and injectable microneedle device-based siRNA administration were examined at the belly site of the mice, and injectable microneedle device showed higher knockdown efficiency than silicon microneedle array patch. This study sets the stage not only for future treatment of TAO-related proptosis using AdPLA siRNA, but also provides the foundation for targeted siRNA delivery by using microneedles.

Smart fibers for energy conversion and storage.

Fibers have played a critical role in the long history of human development. They are the basic building blocks of textiles. Synthetic fibers not only make clothes stronger and more durable, but are also customizable and cheaper. The growth of miniature and wearable electronics has promoted the development of smart and multifunctional fibers. Particularly, the incorporation of functional semiconductors and electroactive materials in fibers has opened up the field of fiber electronics. The energy supply system is the key branch for fiber electronics. Herein, after a brief introduction on the history of smart and functional fibers, we review the current state of advanced functional fibers for their application in energy conversion and storage, focusing on nanogenerators, solar cells, supercapacitors and batteries. Subsequently, the importance of the integration of fiber-shaped energy conversion and storage devices via smart structure design is discussed. Finally, the challenges and future direction in this field are highlighted. Through this review, we hope to inspire scientists with different research backgrounds to enter this multi-disciplinary field to promote its prosperity and development and usher in a truly new era of smart fibers.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvß3 integrin/FAK-MAPK axis in ICC.

Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in nontumor tissues and sera of unaffected individuals. Overexpression of LOXL1 in RBE and 9810 cell lines promoted cell proliferation, colony formation, and metastasis in vivo and in vitro and induced angiogenesis. In contrast, depletion of LOXL1 showed the opposite effects. We further showed that LOXL1 interacted with fibulin 5 (FBLN5), which regulates angiogenesis, through binding to the αvß3 integrin in an arginine-glycine-aspartic (Arg-Gly-Asp) domain-dependent mechanism and enhanced the focal adhesion kinase (FAK)-mitogen-activated protein kinase (MAPK) signaling pathway inside vascular endothelial cells. Our findings shed light on the molecular mechanism underlying LOXL1 regulation of angiogenesis in ICC development and indicate that the LOXL1-FBLN5/αvß3 integrin/FAK-MAPK axis might be the critical pathological link leading to angiogenesis in ICC.