Transdermal Sustained Release Properties and Anti-Photoaging Efficacy of Liposome-Thermosensitive Hydrogel System.

Drug delivery systems have become a research priority in the biomedical field. The incorporation of liposomes to hydrogels further forms more robust multifunctional systems for more effective and sustained topical drug delivery. In this study, carboxymethyl-modified chitosan/hyaluronic acid (CMC/HA, CMH) thermosensitive hydrogel is developed for sustained transdermal delivery of liposomes. Hydrogels are crosslinked by hydrogen bonding, hydrophobic interaction and electrostatic interaction. The gel properties can be regulated by substitution degree (DS), and when DS = 18.20 ± 0.67% (CMH2), the gel temperature is 37.8 °C, allowing rapid gelation at body temperature (315 s). Moreover, CMH2 hydrogel has suitable spreadability (17.7-57.2 cm2 ), viscosity (2133.4 mPa s) and porous structure, which facilitated its adhesion and application on the skin and liposomes delivery. The hydrogel can retard the liposomes release, and the release rate of ascorbyl glucoside (AA2G) is 33.92-49.35% in 24 h. Hydrogel avoids the rapid clearance of liposomes from the skin and improved the skin retention, achieving the long-term release of bioactive components. Liposome-hydrogel system more efficiently promotes the anti-photoaging effect of AA2G on skin, reducing epidermal thickness, melanin deposition and lipid oxidative damage and increasing collagen density. Therefore, liposome-hydrogel systems are proposed as multifunctional delivery systems for sustained transdermal delivery.

Comprehensive Analysis for Predicting Prognoses and Immune Responses of m6A-Related lncRNAs in Women with Lung Adenocarcinoma.

During the past decade, the average 5-year survival rate of patients with Lung adenocarcinoma (LUAD) has remained < 20%, although the targeted therapies and novel immunotherapy approaches have held promise. Epigenetic modifications could provide prognostic value as molecular biomarkers, and we aimed to identify the independent risk of m6A-related lncRNAs to establish a risk model for the clinical prediction of prognoses in women with LUAD. In this study, we first assessed 31 N6-methyladenosine (m6A)-related lncRNAs associated with overall survival. Moreover, we evaluated the expression of the oncogenic driver and the tumor immune microenvironment (TIME) in two female LUAD subtypes (clusters 1 and 2) using consensus clustering. We also found 16 m6A-related lncRNAs as the independent prognostic indicator of women with LUAD and established a risk model developed from these lncRNAs. We comprehensively investigated the correlation between the TIME and m6A-related lncRNA and found that m6A-related lncRNA may significantly affect the immune cell infiltration level in LUAD. In conclusion, our study provides evidence on the prognostic prediction in women with LUAD and may help elucidate the processes and mechanisms of m6A-regulated lncRNAs.

Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology.

Association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery.

Postoperative acute kidney injury (AKI) is a prevalent condition and associated with increased morbidity and mortality following cardiac surgery. This study aimed to investigate the association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery. This retrospective cohort study included patients aged from 1 month to 5 years who underwent congenital heart surgery with cardiopulmonary bypass at the Second Xiangya Hospital of Central South University from January 2016 to March 2022. On the basis of the percentile of body mass index (BMI) for age and sex, eligible participants were divided into three nutritional groups: normal bodyweight, underweight (BMI P5), and obesity (BMI P95). Primary outcomes included postoperative AKI and major adverse kidney events within 30 days (MAKE30). Multivariable logistic regression was performed to determine the association of underweight and obesity with postoperative outcomes. The same analyses were reproduced for classifying patients using weight-for-height instead of BMI. A total of 2,079 eligible patients were included in the analysis, including 1,341 (65%) patients in the normal bodyweight group, 683 (33%) patients in the underweight group, and 55 (2.6%) patients in the obesity group. Postoperative AKI (16% vs. 26% vs. 38%; P < 0.001) and MAKE30 (2.5% vs. 6.4% vs. 9.1%; P < 0.001) were more likely to occur in the underweight and obesity groups. After adjusting for potential confounders, underweight (OR1.39; 95% CI 1.08-1.79; P = 0.008) and obesity (OR 3.85; 95% CI 1.97-7.50; P < 0.001) were found to be associated with an increased risk of postoperative AKI. In addition, both underweight (OR 1.89; 95% CI 1.14-3.14; P = 0.014) and obesity (OR 3.14; 95% CI 1.08-9.09; P = 0.035) were independently associated with MAKE30. Similar results were also found when weight-for-height was used instead of BMI.    Conclusion: In infants and young children undergoing congenital heart surgery, underweight and obesity are independently associated with postoperative AKI and MAKE30. These results may help assess prognosis in underweight and obese patients, and will guide future quality improvement efforts. What is Known: • Postoperative acute kidney injury (AKI) is prevalent and associated with increased morbidity and mortality following pediatric cardiac surgery. • Major adverse kidney events within 30 days (MAKE30) have been recommended as a patient-centered endpoint for evaluating AKI clinical trajectories. A growing concern arises for underweight and obesity in children with congenital heart disease. What is New: • Prevalence of underweight and obesity among infants and young children undergoing congenital heart surgery was 33% and 2.6%, respectively. • Both underweight and obesity were independently associated with postoperative AKI and MAKE30 following congenital heart surgery.

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape.

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10-8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.

Fabrication of high strength cold-set sodium alginate/whey protein nanofiber double network hydrogels and their interaction with curcumin.

Enhancing the bio-based hydrogels strength is fundamental to extend their engineering applications. In this study, high strength cold-set sodium alginate/whey protein nanofiber (SA/WPN) double network hydrogels were prepared and their interaction with curcumin (Cur) was studied. Our results indicated that the rheological and textural properties of SA/WPN double network hydrogels were enhanced with increasing WPN by forming SA-COO--Ca2+--OOC-WPN bridge through electrostatic interactions. The storage modulus (768.2 Pa), hardness (273.3 g), adhesiveness (318.7 g·sec) and cohesiveness (0.464) of SA/WPN50 (WPN concentration of 50 mg/mL) double network hydrogels were 3.75, 2.26, 3.76 and 2.19 times higher than those of SA hydrogels, respectively. Cur was combined with SA/WPN hydrogels through hydrogen bonding, van der Waals forces and hydrophobic interactions with an encapsulation efficiency of 91.6 ± 0.8 %, and the crystalline state was changed after binding. In conclusion, SA/WPN double network hydrogels can be enhanced by the addition of WPN and have potential as carriers for hydrophobic bioactive substances.

Scalp hair loss is not random across follicular units: A new insight into human hair ageing.

OBJECTIVES: Scalp hair has the greatest number of hairs (typically 1-5) per follicular unit but is also the most susceptible body site to hair loss with age. Hence, we set-out to determine the degree to which scalp hair parameters change with age in women and men, any sex differences thereof and whether hair loss is random across follicular units. METHODS: A retrospective cross-sectional study of 200 Chinese men and 200 Chinese women (30-69 years). Image analysis and manual counting methods were used to measure occipital located hair parameters from 6 × 8 mm shaved scalp photographs and plucked hair microscopy images. RESULTS: Of the five hair parameters, the number of hairs per follicular unit had the greatest (negative) correlation with age in both men and women. Men had a greater number of hairs and follicular units than women on average but had a greater decrease in the number of hairs per follicular unit with age, particularly for the loss of multi-hair (3+) follicular units. The loss of hairs with age was significantly different to that expected by a random loss of hairs across follicular units and better described by a model of increased hair loss risk the greater number of hairs per follicular unit. CONCLUSIONS: We have found evidence of hair loss preferentially occurring in multi-hair follicular units, which was more pronounced in men. These data suggest that part of the reason scalp hair is more susceptible to hair loss than on other body sites is due to the greater presence of multi-hair follicular units on the scalp.

OBJECTIFS: Le cuir chevelu possède le plus grand nombre de cheveux (généralement de 1 à 5) par unité folliculaire, mais c'est aussi le site le plus sensible à la perte de cheveux avec l'âge. Nous avons donc entrepris de déterminer dans quelle mesure les paramètres des cheveux du cuir chevelu changent avec l'âge chez les femmes et les hommes, quelles sont les différences entre les sexes et si la perte de cheveux est aléatoire entre les unités folliculaires. MÉTHODES: Étude transversale rétrospective portant sur 200 hommes et 200 femmes chinois (30-69 ans). Des méthodes d'analyse d'image et de comptage manuel ont été utilisées pour mesurer les paramètres des cheveux situés dans la région occipitale à partir de photographies du cuir chevelu rasé de 6x8 mm et d'images microscopiques de cheveux arrachés. RÉSULTATS: Parmi les 5 paramètres capillaires, le nombre de cheveux par unité folliculaire présentait la corrélation la plus forte (négative) avec l'âge, tant chez les hommes que chez les femmes. Les hommes avaient en moyenne un plus grand nombre de cheveux et d'unités folliculaires que les femmes, mais le nombre de cheveux par unité folliculaire diminuait davantage avec l'âge, en particulier pour la perte d'unités folliculaires à plusieurs cheveux (3+). La perte de cheveux avec l'âge était significativement différente de celle attendue par une perte aléatoire de cheveux dans les unités folliculaires, et mieux décrite par un modèle d'augmentation du risque de perte de cheveux plus le nombre de cheveux par unité folliculaire est élevé. CONCLUSIONS: Nous avons trouvé des preuves que la perte de cheveux se produit préférentiellement dans les unités folliculaires à plusieurs cheveux, ce qui était plus prononcé chez les hommes. Ces données suggèrent qu'une partie de la raison pour laquelle les cheveux du cuir chevelu sont plus sensibles à la perte de cheveux que sur d'autres sites du corps est due à la plus grande présence d'unités folliculaires à cheveux multiples sur le cuir chevelu.

Successful biventricular repair in a 14-year-old patient of asplenia with congenital heart disease syndrome.

Heterotaxy syndrome is a rare disease, and asplenia with congenital heart disease syndrome, also known as Ivemark syndrome, is a special form of heterotaxy syndrome. These patients usually have severe cardiovascular malformations and a poor prognosis. Their surgical outcomes are rarely satisfactory. We report the case of a 14-year-old patient who underwent successful corrective surgery treatment.

Decellularized bovine jugular vein and hand-sewn ePTFE valved conduit for right ventricular outflow tract reconstruction in children undergoing Ross procedure.

Background: The Ross procedure is recommended as an optimal aortic valve replacement (AVR) in children and young adults due to several advantages. Nevertheless, multiple reconstructions of the right ventricular outflow tract (RVOT) with new valve conduits have caused some concern regarding the durability of the Ross AVR. Decellularized bovine jugular vein conduit (BJVC) (DP-BJVC) and hand-sewn expanded polytetrafluoroethylene valved conduits (ePTFE VC) are widely employed to reconstruct the RVOT with satisfactory long-term outcomes. However, few studies have compared the safety and efficacy between the two valve conduits. We aimed to evaluate the early outcomes and report our single center experience in the application of these conduits. Methods: Twenty-two pediatric patients (aged < 18 years) who underwent Ross procedures with DP-BJVC and ePTFE VC in our center between 1 June, 2017 and 31 January, 2022 were enrolled. The Kaplan-Meier method was used to evaluate survival, freedom from RVOT reintervention, and freedom from RVOT graft dysfunction. Mixed-effects analysis with the Geisser-Greenhouse correction and Sidak's multiple comparisons test for post-hoc analysis was employed to compare the peak gradient across the conduit at varying follow-ups. Results: All patients were followed up in full. The total early survival rate was 90.9%; two patients in the DP-BJVC group died. There was no significant difference in early mortality, cross-clamp time (p = 0.212), in-hospital stay (p = 0.469), and RVOT graft thrombosis or endocarditis between the two groups. There was similarly no significant difference between Kaplan-Meier freedom from RVOT graft dysfunction curve (P = 0.131). The transprosthetic gradient gradually increased over time in both groups and was significantly higher in the DP-BJVC group at follow-up (P < 0.05). Conclusions: Both conduits show excellent early and midterm outcomes for RVOT reconstruction in the Ross procedure. We suggest that DP-BJVC is more suitable for infants, and ePTFE conduit is more suitable for older children who require larger conduits.

Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying.

Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors' depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition.

Genetic variants underlying differences in facial morphology in East Asian and European populations.

Facial morphology-a conspicuous feature of human appearance-is highly heritable. Previous studies on the genetic basis of facial morphology were performed mainly in European-ancestry cohorts (EUR). Applying a data-driven phenotyping and multivariate genome-wide scanning protocol to a large collection of three-dimensional facial images of individuals with East Asian ancestry (EAS), we identified 244 variants in 166 loci (62 new) associated with typical-range facial variation. A newly proposed polygenic shape analysis indicates that the effects of the variants on facial shape in EAS can be generalized to EUR. Based on this, we further identified 13 variants related to differences between facial shape in EUR and EAS populations. Evolutionary analyses suggest that the difference in nose shape between EUR and EAS populations is caused by a directional selection, due mainly to a local adaptation in Europeans. Our results illustrate the underlying genetic basis for facial differences across populations.

Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Olive oil effectively mitigates ovariectomy-induced marrow adiposity assessed by MR spectroscopy in estrogen-deficient rabbits.

BACKGROUND: Polyphenols in extra virgin olive oil (EVOO) have been found to reduce the expression of PPARγ2, inhibit adipocyte differentiation, and enhance the formation of osteoblasts from bone marrow stem cells. However, the underlying mechanisms of their action remain unknown. PURPOSE: To determine the sequential effects of EVOO on marrow fat expansion induced by estrogen deprivation using 3.0-T proton magnetic resonance (MR) spectroscopy in an ovariectomy (OVX) rabbit model of postmenopausal bone loss over a six-month period. MATERIAL AND METHODS: A total of 45 female New Zealand rabbits were equally divided into sham-operation, OVX controls, and OVX treated with EVOO for six months. Marrow fat fraction was measured by MR spectroscopy at baseline conditions, and three and six months postoperatively, respectively. Serum bone biomarkers, lumbar and femoral bone mineral density, microtomographic parameters, biomechanical properties, and quantitative parameters of marrow adipocytes were studied. RESULTS: OVX was associated with marrow adiposity in a time-dependent manner, accompanied with increased bone turnover and impaired bone mass and trabecular microarchitecture. In OVX rabbits, EVOO markedly alleviated trabecular bone loss and reduced the accumulation of lipid droplets including adipocyte size, density, and areas of fat deposits in the bone marrow. EVOO prevented such changes in terms of both marrow adiposity and bone remodeling. CONCLUSION: Early EVOO treatment may exert beneficial effects on bone by modulating marrow adiposity, which would support their protective effect against bone pathologies.

Gender Difference is Associated with Short-Term Outcomes in Non-Surgically Managed Acute Aortic Dissection Patients with Hypertension: A Retrospective Cohort Study.

BACKGROUND: The management of acute aortic dissection (AAD) has improved; however, the outcomes related to different gender with short-term outcomes in non-surgically managed AAD with hypertension are still limited. Our objective was to explore gender-differences in association with short-term outcomes of patients comorbid with hypertension in non-surgically managed AAD. METHODS: This is an observational retrospective single-center cohort. We analyzed the data from the Second Xiangya Hospital of Central South University (2014-2018). The data on demographics, clinical presentation, chronic comorbidities, laboratory testing, imaging studies, and treatment were analyzed for all patients. Univariate and multiple analyses were used to test gender-difference associated with short-term outcomes of patients with hypertension in non-surgically managed AAD. RESULTS: In total, 288 patients were enrolled in this study, of whom 238 (82.63%) were male and 50 (17.37%) were females. About 74% of female patients were dead in-hospital, which was more than male patients (56.3%). Female patients with diabetes mellitus were more than male patients (14% vs 2.94%), while male patients with smoking were significant higher than female patients (36.55% vs 8%). In the full model (model 3), after adjusting for confounding variables, the female AAD patients were more likely to have worse short-term outcomes (OR=3.60, 95% CI=1.41 to 9.60). CONCLUSION: Female patients were more likely to have worse outcomes in non-surgically managed AAD patients with hypertension. Large numbers of investigations are required to further explore this relationship.

A genome-wide association study of facial morphology identifies novel genetic loci in Han Chinese.

The human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack of studies on the Han Chinese population. Here, we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology. We identify single-nucleotide polymorphisms (SNPs) encompassing four genomic regions showing significant associations with different facial regions, including SNPs in DENND1B associated with the chin, SNPs among PISRT1 associated with eyes, SNPs between DCHS2 and SFRP2 associated with the nose, and SNPs in VPS13B associated with the nose. We replicate 24 SNPs from previously reported genetic loci in different populations, whose candidate genes are DCHS2, SUPT3H, HOXD1, SOX9, PAX3, and EDAR. These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.

Two new layered metal chalcogenide frameworks as photocatalysts for highly efficient and selective dye degradation.

Dye photodegradation is an important research topic, and great efforts have been made to target the photocatalysts with highly efficient and selective performance. Reported here are two layered anion chalcogenide frameworks with semiconducting properties combined with highly open interlayer spaces, which are used as efficient photocatalysts to show excellent size and charge selectivity towards organic dye molecules. In addition, the organic templates inside the chalcogenide frameworks are exchanged via an ion-exchange process, and the resulting host frameworks with much looser internal spaces play significant roles in improving the photocatalytic activity.

A cell-type deconvolution meta-analysis of whole blood EWAS reveals lineage-specific smoking-associated DNA methylation changes.

Highly reproducible smoking-associated DNA methylation changes in whole blood have been reported by many Epigenome-Wide-Association Studies (EWAS). These epigenetic alterations could have important implications for understanding and predicting the risk of smoking-related diseases. To this end, it is important to establish if these DNA methylation changes happen in all blood cell subtypes or if they are cell-type specific. Here, we apply a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven large EWAS. We find that most of the highly reproducible smoking-associated hypomethylation signatures are more prominent in the myeloid lineage. A meta-analysis further identifies a myeloid-specific smoking-associated hypermethylation signature enriched for DNase Hypersensitive Sites in acute myeloid leukemia. These results may guide the design of future smoking EWAS and have important implications for our understanding of how smoking affects immune-cell subtypes and how this may influence the risk of smoking related diseases.

A Photoconductive X-ray Detector with a High Figure of Merit Based on an Open-Framework Chalcogenide Semiconductor.

A wide range of tunability in the physical parameters of a semiconductor used for X-ray detection is desirable to achieve targeted performance optimization. However, in a dense-phase semiconductor, fine-tuning one parameter often leads to unwanted changes in other parameters. Herein, the intrinsic openness in an open-framework semiconductor has been confirmed, for the first time, to be a key structural factor that weakens the mutual exclusivity of the adjustable physical parameters owing to a non-linear control mechanism. The controllable doping of S in a zeolitic In-Se host results in an optimal balance between resistivity, band gap, and carrier mobility, which finally results in an excellent X-ray detector with a high figure of merit for the mobility-lifetime product (7.12×10-4  cm2 V-1 ); this value is superior to that of a commercial α-Se detector. The current strategy of choosing open-framework semiconductor materials opens a new window for targeting high-performance X-ray detection.

Denitrifier communities differ in mangrove wetlands across China.

To explore the geographical variations in the nosZ-denitrifier community and the underlying influential factors, surface sediments were collected from six mangroves across China, including Yunxiao (YX), Futian (FT), Fangchenggang (FCG), Zhanjiang (ZJ), Dongzhaigang (DZG), and Dongfang (DF). The nosZ gene abundance in mangrove sediments were 1.60 × 105-1.17 × 106 copies g-1 dry sediment, with a higher density in Avicennia marina forest than the mudflat. Denitrifier community richness and diversity increased with decreasing latitude based on the Chao1 richness and Shannon diversity index, with the highest diversity being observed in the DF mangrove. The denitrifier communities could be classified into three groups including south DF mangrove, middle FCG, ZJ and DZG mangroves, and north YX and FT mangroves based on HCA and PCoA analysis. The nosZ OTUs could be divided into seven distinct clusters with different proportionality characteristics among mangroves. Environmental factors (TN, TOC, and salinity) collectively shape denitrifier communities in mangrove sediments.