Pumping Small Molecules Selectively through an Energy-Assisted Assembling Process at Nonequilibrium States.

In living organisms, precise control over the spatial and temporal distribution of molecules, including pheromones, is crucial. This level of control is equally important for the development of artificial active materials. In this study, we successfully controlled the distribution of small molecules in the system at nonequilibrium states by actively transporting them, even against the apparent concentration gradient, with high selectivity. As a demonstration, in the aqueous solution of acid orange (AO7) and TMC10COOH, we found that AO7 molecules can coassemble with transient anhydride (TMC10CO)2O to form larger assemblies in the presence of chemical fuel 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC). This led to a decrease in local free AO7 concentration and caused AO7 molecules from other locations in the solution to move toward the assemblies. Consequently, AO7 accumulates at the location where EDC was injected. By continuously injecting EDC, we could maintain a stable high value of the apparent AO7 concentration at the injection point. We also observed that this process which operated at nonequilibrium states exhibited high selectivity.

Anion-Dominated Solvation in Low-Concentration Electrolytes Promotes Inorganic-Rich Interphase Formation in Lithium Metal Batteries.

While the formation of an inorganic-rich solid electrolyte interphase (SEI) plays a crucial role, the persistent challenge lies in the formation of an organic-rich SEI due to the high solvent ratio in low-concentration electrolytes (LCEs), which hinders the achievement of high-performance lithium metal batteries. Herein, by incorporating di-fluoroethylene carbonate (DFEC) as a non-solvating cosolvent, a solvation structure dominated by anions is introduced in the innovative LCE, leading to the creation of a durable and stable inorganic-rich SEI. Leveraging this electrolyte design, the Li||NCM83 cell demonstrates exceptional cycling stability, maintaining 82.85% of its capacity over 500 cycles at 1 C. Additionally, Li||NCM83 cell with a low N/P ratio (≈2.57) and reduced electrolyte volume (30 µL) retain 87.58% of its capacity after 150 cycles at 0.5 C. Direct molecular information is utilized to reveal a strong correlation between solvation structures and reduction sequences, proving the anion-dominate solvation structure can impedes the preferential reduction of solvents and constructs an inorganic-rich SEI. These findings shed light on the pivotal role of solvation structures in dictating SEI composition and battery performance, offering valuable insights for the design of advanced electrolytes for next-generation lithium metal batteries.

Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients.

BACKGROUND: Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. METHODS: We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618-0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714-46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415-5.811, p = 0.040). CONCLUSIONS: Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism.

BACKGROUND: FGF8-FGFR1 signalling is involved in multiple biological processes, while impairment of this signalling is one of the main reasons for isolated hypogonadotropic hypogonadism (IHH). Recently, several negative modulators of FGF8-FGFR1 signalling were also found to be involved in IHH, including DUSP6, IL17RD, SPRY2 and SPRY4. The aim of this study was to investigate the genotypic and phenotypic spectra of these genes in a large cohort of Chinese patients with IHH. METHODS: A total of 196 patients with IHH were enrolled in this study. Whole-exome sequencing was performed to identify variants, which was verified by PCR and Sanger sequencing. RESULTS: Four heterozygous DUSP6 variants (p.S157I, p.R83Q, p.P188L and p.N355I) were found in six patients. Cryptorchidism, dental agenesis, syndactyly and blue colour blindness were commonly observed in patients with DUSP6 mutations. Six heterozygous IL17RD variants (p.P191L, p.G35V, p.S671L, p.A221T, p.I329M and p.I329V) were found in seven patients. Segregation analysis indicated that 100% (5/5) of probands inherited the IL17RD variants from their unaffected parents, and oligogenicity was found in 4/7 patients. One rare SPRY4 variant (p.T68S) was found in a female patient with Kallmann syndrome who also carried a PLXNA1 mutation. CONCLUSION: Our study greatly enriched the genotypic and phenotypic spectra of DUSP6, IL17RD and SPRY4 in IHH. Mutations in DUSP6 alone seem sufficient to cause IHH in an autosomal dominant manner, whereas IL17RD or SPRY4 mutations may cause IHH phenotypes in synergy with variants in other IHH-associated genes.

ANOS1 variants in a large cohort of Chinese patients with congenital hypogonadotropic hypogonadism. / ä¸­å›½å ˆå¤©æ€§ä½Žä¿ƒæ€§è ºæ¿€ç´ æ€§æ€§è ºåŠŸèƒ½å‡é€€ç—‡æ‚£è€ ANOS1的突变.

OBJECTIVES: Congenital hypogonadotropic hypogonadism (CHH) is a rare congenital gonadal dysplasia caused by defects in the synthesis, secretion or signal transduction of hypothalamic gonadotropin releasing hormone. The main manifestations of CHH are delayed or lack puberty, low levels of sex hormones and gonadotropins, and may be accompanied with other clinical phenotypes. Some patients with CHH are also accompanied with anosmia or hyposmia, which is called Kalman syndrome (KS). ANOS1, located on X chromosome, is the first gene associated with CHH in an X-linked recessive manner. This study aims to provide a basis for the genetic diagnosis of CHH by analyzing the gene variant spectrum of ANOS1 in CHH and the relationship between clinical phenotype and genotype. METHODS: In this study, whole exome sequencing (WES) was used to screen rare sequencing variants (RSVs) of ANOS1 in a Chinese cohort of 165 male CHH patients. Four commonly used in silico tools were used to predict the function of the identified RSVs in coding region, including Polyphen2, Mutation Taster, SIFT, and Combined Annotation Dependent Depletion (CADD). Splice Site Prediction by Neural Network (NNSPLICE) was employed to predict possibilities of intronic RSVs to disrupt splicing. American College of Medical Genetics and Genomics (ACMG) guidelines was used to assess the pathogenicity of the detected RSVs. The ANOS1 genetic variant spectrum of CHH patients in Chinese population was established. The relationship between clinical phenotype and genotype was analyzed by collecting detailed clinical data. RESULTS: Through WES analysis for 165 CHH patients, ANOS1 RSVs were detected in 17 of them, with the frequency of 10.3%. A total of 13 RSVs were detected in the 17 probands, including 5 nonsense variants (p.T76X, p.R191X, p.W257X, p.R262X, and p.W589X), 2 splicing site variants (c.318+3A>C, c.1063-1G>C), and 6 missense variants (p.N402S, p.N155D, p.P504L, p.C157R, p.Q635P, and p.V560I). In these 17 CHH probands with ANOS1 RSVs, many were accompanied with other clinical phenotypes. The most common associated phenotype was cryptorchidism (10/17), followed by unilateral renal agenesis (3/17), dental agenesis (3/17), and synkinesia (3/17). Eight RSVs, including p.T76X, p.R191X, p.W257X, p.R262X, p.W589X, c.318+3A>C, c.1063-1G>C, and p.C157R, were predicted to be pathogenic or likely pathogenic ANOS1 RSVs by ACMG. Eight CHH patients with pathogenic or likely pathogenic ANOS1 variants had additional features. In contrast, only one out of nine CHH patients with non-pathogenic (likely benign or uncertain of significance) ANOS1 variants according to ACMG exhibited additional features. And function of the non-pathogenic ANOS1 variants accompanied with other CHH-associated RSVs. CONCLUSIONS: The ANOS1 genetic spectrum of CHH patients in Chinese population is established. Some of the correlations between clinical phenotype and genotype are also established. Our study indicates that CHH patients with pathogenic or likely pathogenic ANOS1 RSVs tend to exhibit additional phenotypes. Although non-pathogenic ANOS1 variants only may not be sufficient to cause CHH, they may function together with other CHH-associated RSVs to cause the disease.

The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab.

Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products.

Hexabenzocoronene Graphitic Nanocoils Appended with Crown Ethers: Supramolecular Chirality Induced by Host-Guest Interaction.

We have designed and synthesized two new achiral hexa-peri-hexabenzocoronene (HBC) derivatives, HBCCE and HBCTEG-CE , which bear the crown ether as the pendant for the amino acid binding site. The HBCCE self-assembled into a racemic mixture of P- and M-handed helical nanocoils, however, in the presence of chiral amino acid guests, it formed helical nanocoils with one-handed screw sense. The effects of the concentration, type and configuration of the guests on the induced circular dichroism (ICD) during the co-assembly of HBCCE with chiral amino acids were also investigated. Additionally, after complete removal of the chiral guests, the optically active nanocoils did not racemize, even in the presence of excess amino acids with the opposite configuration. In contrast, HBCTEG-CE with a long triethylene glycol (TEG) chain between the crown ether group and the HBC unit did not exhibit ICD during the co-assembly with chiral amino acids.

Highly Sensitive Room-Temperature Detection of Ammonia in the Breath of Kidney Disease Patients Using Fe2Mo3O8/MoO2@MoS2 Nanocomposite Gas Sensor.

A novel Fe2Mo3O8/MoO2@MoS2 nanocomposite is synthesized for extremely sensitive detection of NH3 in the breath of kidney disease patients at room temperature. Compared to MoS2, α-Fe2O3/MoS2, and MoO2@MoS2, it shows the optimal gas-sensing performance by optimizing the formation of Fe2Mo3O8 at 900 °C. The annealed Fe2Mo3O8/MoO2@MoS2 nanocomposite (Fe2Mo3O8/MoO2@MoS2-900 °C) sensor demonstrates a remarkably high selectivity of NH3 with a response of 875% to 30 ppm NH3 and an ultralow detection limit of 3.7 ppb. This sensor demonstrates excellent linearity, repeatability, and long-term stability. Furthermore, it effectively differentiates between patients at varying stages of kidney disease through quantitative NH3 measurements. The sensing mechanism is elucidated through the analysis of alterations in X-ray photoelectron spectroscopy (XPS) signals, which is supported by density functional theory (DFT) calculations illustrating the NH3 adsorption and oxidation pathways and their effects on charge transfer, resulting in the conductivity change as the sensing signal. The excellent performance is mainly attributed to the heterojunction among MoS2, MoO2, and Fe2Mo3O8 and the exceptional adsorption and catalytic activity of Fe2Mo3O8/MoO2@MoS2-900 °C for NH3. This research presents a promising new material optimized for detecting NH3 in exhaled breath and a new strategy for the early diagnosis and management of kidney disease.

TCFormer: Visual Recognition via Token Clustering Transformer.

Transformers are widely used in computer vision areas and have achieved remarkable success. Most state-of-the-art approaches split images into regular grids and represent each grid region with a vision token. However, fixed token distribution disregards the semantic meaning of different image regions, resulting in sub-optimal performance. To address this issue, we propose the Token Clustering Transformer (TCFormer), which generates dynamic vision tokens based on semantic meaning. Our dynamic tokens possess two crucial characteristics: (1) Representing image regions with similar semantic meanings using the same vision token, even if those regions are not adjacent, and (2) concentrating on regions with valuable details and represent them using fine tokens. Through extensive experimentation across various applications, including image classification, human pose estimation, semantic segmentation, and object detection, we demonstrate the effectiveness of our TCFormer. The code and models for this work are available at https://github.com/zengwang430521/TCFormer.

Chemical energy assisted self-assembling of a porphyrin-substituted benzoic acid in complex environments.

Energy input plays a crucial role in the assembling of matter. In our present study, we utilize EDC as a chemical fuel to drive the molecular assembling of POR-COOH. POR-COOH will react with EDC to generate the intermediate POR-COOEDC first, which was well-solvated by solvent molecules. During the subsequent hydrolysis process, EDU and oversaturated POR-COOH molecules at high energy states will be formed and thus allowed the self-assembling of POR-COOH into 2D nanosheets. This chemical energy assisted assembling process could be performed not only under mild conditions with high spatial accuracy but also with high selectivity in complex environments.

The Role of Albumin in the Diagnosis of Neonatal Sepsis Over the Last 11 Years: A Retrospective Study.

Background: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together. Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy. Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P<0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB. Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy.

INTRODUCTION: To analyze the associations of circulating C1q/tumor necrosis factor-related protein-3 (CTRP3) concentrations with several metabolic parameters and to investigate the possible role of CTRP3 in subjects with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: A total of 347 participants were recruited in this study, and plasma CTRP3 concentrations were analyzed in subjects with DPN (n=172) and without DPN (non-DPN, n=175). The nerve conduction test and oral glucose tolerance test were performed, and Neuropathy Symptom Score (NSS)/Neuropathy Disability Score (NDS) and biochemical parameters were measured in all participants. RESULTS: Plasma CTRP3 concentrations were significantly lower in patients with DPN compared with those in patients with diabetes without DPN (p<0.01), despite the comparable glucose and lipid metabolism levels in both groups. Groups with a higher plasma CTRP3 level had a faster nerve conduction velocity. In addition, plasma CTRP3 concentrations were negatively correlated with hemoglobin A1c (HbA1c), urea acid (UA), triglyceride, NSS and NDS (p<0.05) after being adjusted for age and sex. Multivariate logistic regression analysis revealed that plasma CTRP3 concentrations were significantly correlated with DPN after being controlled for age, sex, body mass index, HbA1c, blood pressure, lipid profiles, and renal function. CONCLUSIONS: Plasma CTRP3 concentrations were significantly lower in patients with DPM and positively correlated with nerve conduction velocity. The relationship between CTRP3 levels and DPN is independent of the glucose and lipid status. Therefore, circulating CTRP3 might serve as a predictor of impairment of nerve conduction in patients with DPN.

Circadian Rhythm Sleep Disorders: Genetics, Mechanisms, and Adverse Effects on Health.

Nearly all living organisms, from cyanobacteria to humans, have an internal circadian oscillation with a periodicity of approximately 24 h. In mammals, circadian rhythms regulate diverse physiological processes including the body temperature, energy metabolism, immunity, hormone secretion, and daily sleep-wake cycle. Sleep is tightly regulated by circadian rhythms, whereas a misalignment between the circadian rhythms and external environment may lead to circadian rhythm sleep disorders (CRSD). CRSD includes four main kinds of disorders: the advanced sleep-wake phase disorder (ASPD), the delayed sleep-wake phase disorder (DSPD), the irregular sleep-wake rhythm disorder and the non-24-h sleep-wake rhythm disorder. Recent studies have begun to shed light on the genetic basis of CRSD. Deciphering the genetic codes for ASPD and DSPD has so far been more successful than the other CRSDs, which allow for the development of animal models and understanding of the pathological mechanisms for these disorders. And studies from humans or animal models implicate CRSDs are associated with adverse health consequences, such as cancer and mental disorders. In this review, we will summarize the recent advances in the genetics, underlying mechanisms and the adverse effects on health of ASPD and DSPD.

Immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac) co-administered with an inactivated quadrivalent influenza vaccine: A randomized, open-label, controlled study in healthy adults aged 18 to 59 years in China.

BACKGROUND: Studies are needed for evidence of inactivated COVID-19 vaccine co-administered with influenza vaccine. METHODS: A randomized, open-label, controlled study was conducted in Zhejiang Province, China. Eligible healthy adults aged 18-59 years underwent randomization at a ratio of 1:1:2 to receive inactivated quadrivalent influenza vaccine (IIV4) either concomitantly with the first (C1 subgroup) or the second (C2 subgroup) dose of CoronaVac, or 14 days after the first dose of CoronaVac (S group). The primary purpose of the study was to prove the non-inferiority in seroconversion rate of antibody against SARS-CoV-2. RESULTS: Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the C1, C2, and S groups, respectively. As lower bound of the two-sided 95% confidence interval (CI) of the difference for the seroconversion rate of antibodies against SARS-CoV-2 was over -10%, the immune response for CoronaVac in the C group (93.1% [89.0, 96.0]) was non-inferior to that in the S group (95.2% [91.5, 97.6]) in the per-protocol set. A lower GMT of antibody against SARS-CoV-2 was observed in the C group as compared to the S group (27.5 vs. 38.1, P = 0.0001). Decrease of immune response to CoronaVac was mainly observed in participants received IIV4 concomitantly with their second dose of CoronaVac (C2 subgroup), with a seroconversion rate of 89.7% (95CI: 82.6%-94.5%) and a GMT of 23.3. The occurrences of vaccine related adverse reactions were no more than 20% and comparable among different groups. Most of the adverse reactions were mild and moderate. CONCLUSION: Co-administration of inactivated COVID-19 vaccine and seasonal influenza vaccine, especially the administration regimen that the seasonal influenza vaccine co-administered with the first dose of the inactivated COVID-19 vaccine, would be feasible.

SLIT2 Rare Sequencing Variants Identified in Idiopathic Hypogonadotropic Hypogonadism.

INTRODUCTION: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare reproductive disorder resulting from gonadotropin-releasing hormone (GnRH) deficiency. However, in only approximately half of patients with IHH is it possible to identify a likely molecular diagnosis. Mice lacking Slit2 have a reduced number or altered patterning of GnRH neurons in the brain. In order to assess the contribution of SLIT2 to IHH, we carried out a candidate gene burden test analysis. METHODS: A total of 196 IHH probands and 2,362 ethic-matched controls were recruited for this study. The IHH probands and controls were subjected to whole-exome sequencing. In the IHH patients with SLIT2 variants and their available family members, detailed phenotyping and segregation analysis were performed. RESULTS: Nine heterozygous SLIT2 rare sequencing variants (RSVs) were identified in 13 probands, with a prevalence of 6.6%. Furthermore, we identified an increased mutational burden for SLIT2 in this cohort (odds ratio = 2.2, p = 0.021). The segregation analysis of available IHH families revealed that the majority of SLIT2 RSVs were inherited from unaffected or partially affected parents. CONCLUSION: Our study suggests SLIT2 as a new IHH-associated gene and expands the clinical and genetic spectrum of IHH. Furthermore, SLIT2 alone does not appear to be sufficient to cause the disorder, and it may interact with other IHH-associated genes to induce a clinical phenotype.

Discovery of a Novel Variant of SEMA3A in a Chinese Patient with Isolated Hypogonadotropic Hypogonadism.

Semaphorin (SEMA) has an important role in nerve development, organ formation, immune response, angiogenesis, and tumor growth. SEMA can regulate the growth and branching of axons, the morphology of dendrites, and the migration of neurons. The loss-of-function in SEMA and its receptors PLXNs and NRP affect the migration of GnRH neurons, leading to idiopathic hypogonadotropic hypogonadism (IHH). As a member of the SEMA family, SEMA3A has an important role in axonal rejection, dendritic branching, synaptic formation, and neuronal migration. There are more and more SEMA3A variants identified in IHH patients. In this study, we identified a novel SEMA3A variant (c.1369A > G (p.T457A)) in a male nIHH patient. Functional studies indicated that the T457A SEMA3A variant led to the defect of FAK phosphorylation and GN11 cell migration, which strongly argued in favor of its pathogenic effect in the nIHH patient. Our findings substantiated that the 435-457 position of SEMA3A might be very important for the secretion of SEMA3A. Haploin-sufficiency of SEMA3A in humans was sufficient to cause the IHH phenotype. SEMA3A variants might have a role in modifying the IHH phenotype, according to the variants at different positions of SEMA3A. SEMAs and its receptors formed a complex network, and other members of the SEMA-signaling pathway might also be involved in the pathogenesis of IHH.

Tuning the Anisotropic Thermal Transport in {110}-Silicon Membranes with Surface Resonances.

Understanding the thermal transport in nanostructures has important applications in fields such as thermoelectric energy conversion, novel computing and heat dissipation. Using non-homogeneous equilibrium molecular dynamic simulations, we studied the thermal transport in pristine and resonant Si membranes bounded with {110} facets. The break of symmetry by surfaces led to the anisotropic thermal transport with the thermal conductivity along the [110]-direction to be 1.78 times larger than that along the [100]-direction in the pristine structure. In the pristine membranes, the mean free path of phonons along both the [100]- and [110]-directions could reach up to ∼100 µm. Such modes with ultra-long MFP could be effectively hindered by surface resonant pillars. As a result, the thermal conductivity was significantly reduced in resonant structures, with 87.0% and 80.8% reductions along the [110]- and [100]-directions, respectively. The thermal transport anisotropy was also reduced, with the ratio κ110/κ100 decreasing to 1.23. For both the pristine and resonant membranes, the thermal transport was mainly conducted by the in-plane modes. The current work could provide further insights in understanding the thermal transport in thin membranes and resonant structures.

ZNF451 stabilizes TWIST2 through SUMOylation and promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is the process by which epithelial cells lose their tightly packed polarized characteristics and acquire a migratory mesenchymal phenotype. EMT plays a pivotal role in embryonic development, wound healing, tissue regeneration, organ fibrosis and cancer progression. The basic helix-loop-helix (bHLH) transcription factors TWIST1/2 are key EMT-inducing transcription factors that govern transcription of EMT-associated genes. Although regulation of TWIST1 activity and stability has been well studied, little is known about how TWIST2 is post-translationally regulated. Here we have identified ZNF451, a SUMO2/3 specific E3 ligase, as a novel regulator of TWIST2 in promoting its stability. ZNF451 directly binds to and SUMOylates TWIST2 at K129 residue, and consequently blocks ubiquitination and proteasome-dependent degradation of TWIST2. Ectopic expression of ZNF451 increases the protein level of TWIST2 in mammary epithelial cells, leading to increased expression of mesenchymal markers, whereas depletion of ZNF451 suppresses mesenchymal phenotypes. Collectively, our findings demonstrate that ZNF451 plays a vital role in EMT through SUMOylation-dependent stabilization of TWIST2.

Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism.

BACKGROUND: Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin-releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans. METHODS: The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis. RESULTS: We identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH-associated genes. CONCLUSION: Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.

Pulmonary cryptococcosis induces chitinase in the rat.

BACKGROUND: We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of C. neoformans consists of chitin, and since acidic mammalian chitinase (AMCase) has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat. METHODS: We utilized a previously-established model of chronic C. neoformans pulmonary infection in the rat to analyze the activity, expression and localization of AMCase. RESULTS: Our studies indicate that intratracheal inoculation of C. neoformans induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. C. albicans), but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression. CONCLUSION: Our findings indicate a possible link between respiratory fungal infections, including C. neoformans, and asthma through the induction of AMCase.