Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression.

In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells results in complete male sterility, with spermatogenesis ultimately arrested at the zygotene stage of meiosis. KDM2A deficiency disrupts H3K36me2/3 deposition in c-KIT+ germ cells, characterized by a reduction in H3K36me2 but a dramatic increase in H3K36me3. Furthermore, KDM2A recruits the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression, such as Stra8, Meiosin, Spo11, and Sycp1. Collectively, our study unveils an essential role for KDM2A in mediating H3K36me2/3 deposition and controlling the programmed gene expression necessary for the transition from mitosis to meiosis during spermatogenesis.

Tailored Supramolecular Interactions in Host-Guest Complexation for Efficient and Stable Perovskite Solar Cells and Modules.

Host-guest complexation offers a promising approach for mitigating surface defects in perovskite solar cells (PSCs). Crown ethers are the most widely used macrocyclic hosts for complexing perovskite surfaces, yet their supramolecular interactions and functional implications require further understanding. Here we show that the dipole moment of crown ethers serves as an indicator of supramolecular interactions with both perovskites and precursor salts. A larger dipole moment, achieved through the substitution of heteroatoms, correlates with enhanced coordination with lead cations. Perovskite films incorporating aza-crown ethers as additives exhibited improved morphology, reduced defect densities, and better energy-level alignment compared to those using native crown ethers. We report power-conversion efficiencies (PCEs) exceeding 25% for PSCs, which show enhanced long-term stability, and a record PCE of 21.5% for host-guest complexation-based perovskite solar modules with an active area of 14.0 cm2.

Intelligent films based on dual-modified starch and microencapsulated Aronia melanocarpa anthocyanins: Functionality, stability and application.

This study aims to enhance the physical properties and color stability of anthocyanin-based intelligent starch films. Three dual-modified starches, namely crosslinked-oxidized starch (COS), acetylated distarch phosphate (ADSP), and hydroxypropyl distarch phosphate (HDSP), were utilized as film matrices. Aronia melanocarpa anthocyanins were incorporated through three different pre-treatments (free, spray-drying microencapsulation, and freeze-drying microencapsulation) to assess the prepared films' functionality, stability, and applicability. The results indicate that the ADSP film exhibited an approximately two-fold increase in elongation at break (EAB) compared to native starch film. Specifically, the ADSP film's water contact angle (WCA) reached 90°, demonstrating excellent flexibility and hydrophobicity. Scanning electron microscopy (SEM) revealed stronger interactions between anthocyanins and the film matrix after microencapsulation. Furthermore, after 30 days of exposure to 37 °C heat and light radiation, the freeze-dried anthocyanin-based intelligent film (FDA film) exhibited minimal fading, displaying the highest stability among the tested films. Notably, during beef freshness monitoring, the intelligent films underwent significant color changes as the beef deteriorated. In conclusion, the developed FDA film, with its outstanding stability and responsive pH characteristics, holds immense potential as a novel packaging material for food applications.

N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis.

BACKGROUND: The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. RESULTS: We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. CONCLUSIONS: Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Effects of adding proteins from different sources during heat-moisture treatment on corn starch structure, physicochemical and in vitro digestibility.

Proteins impact starch digestion, but the specific mechanism under heat-moisture treatment remains unclear. This study examined how proteins from various sources-white kidney bean, soybean, casein, whey-altered corn starch's structure, physicochemical properties, and digestibility during heat-moisture treatment (HMT). HMT and protein addition could significantly reduce starch's digestibility. The kidney bean protein-starch complex under HMT had the highest resistant starch at 19.74 %. Most proteins effectively inhibit α-amylase, with kidney bean being the most significantly (IC50 = 1.712 ± 0.085 mg/mL). HMT makes starch obtain a more rigid structure, limits its swelling ability, and reduces paste viscosity and amylose leaching. At the same time, proteins also improve starch's short-range order, acting as a physical barrier to digestion. Rheological and low-field NMR analyses revealed that protein enhanced the complexes' shear stability and water-binding capacity. These findings enrich the understanding of how proteins from different sources affect starch digestion under HMT, aiding the creation of nutritious, hypoglycemic foods.

Octenyl succinic anhydride tigernut starch: Structure, physicochemical properties and stability of curcumin-loaded Pickering emulsion.

In recent years, there has been increasing attention to starch particle-stabilized Pickering emulsions. In this study, the tigernut starch (TNS) was isolated from the tigernut meal, and further octenyl succinic anhydride tigernut starch (OSATNS) was prepared by a semi-dry method. The structure of OSATNS was analyzed and characterized by degrees of substitution (DS), contact angle, SEM, and FTIR. OSATNS was then used to stabilize the curcumin-loaded Pickering emulsion to improve the water solubility and stability of the curcumin. The results showed that OSATNS with 3 %-9 % OSA exhibited a DS range of 0.012 to 0.029, and its contact angle increased from 69.23° to 84.76°. SEM revealed that TNS consisted of small starch particles averaging 7.71 µm, and esterification did not significantly alter their morphology or size. FTIR analysis confirmed successful OSA incorporation by revealing two new peaks at 1732 cm-1 and 1558 cm-1. After 7 days of storage, Pickering emulsions stabilized with OSATNS-9 % exhibited superior stability and curcumin retention compared to Tween 80 emulsions, maintaining retention rates above 80 % even after different heat treatments. In conclusion, this study shows the potential application of OSATNS in stabilizing Pickering emulsions and demonstrates its good thermal stability and protection against curcumin during storage.

Oxygen Vacancy Mediation in SnO2 Electron Transport Layers Enables Efficient, Stable, and Scalable Perovskite Solar Cells.

Previous findings have suggested a close association between oxygen vacancies in SnO2 and charge carrier recombination as well as perovskite decomposition at the perovskite/SnO2 interface. Underlying the fundamental mechanism holds great significance in achieving a more favorable balance between the efficiency and stability. In this study, we prepared three SnO2 samples with different oxygen vacancy concentrations and observed that a low oxygen vacancy concentration is conducive to long-term device stability. Iodide ions were observed to easily diffuse into regions with high oxygen vacancies, thereby speeding up the deprotonation of FAI, as made evident by the detection of the decomposition product formamide. In contrast, a high oxygen vacancy concentration in SnO2 could prevent hole injection, leading to a decrease in interfacial recombination losses. To suppress this decomposition reaction and address the trade-off, we designed a bilayer SnO2 structure to ensure highly efficient carrier transport still while maintaining a chemically inert surface. As a result, an enhanced efficiency of 25.06% (certified at 24.55% with an active area of 0.09 cm2 under fast scan) was achieved, and the extended operational stability maintained 90% of their original efficiency (24.52%) after continuous operation for nearly 2000 h. Additionally, perovskite submodules with an active area of 14 cm2 were successfully assembled with a PCE of up to 22.96% (20.09% with an aperture area).

Effect of Cyperus esculentus polysaccharide on Cyperus esculentus starch: Pasting, rheology and in vitro digestibility.

This study investigated the effects of varying amounts of added Cyperus esculentus polysaccharide (CEP) on the physicochemical and structural properties, as well as in vitro digestibility, of homologous Cyperus esculentus starch (CES). Compared to CES, the CES-CEP complexes showed reduced peak viscosity and breakdown value, and improved thermal paste stability of starch. Rheological properties showed that adding CEP reduced the consistency coefficient and pseudoelasticity of the complexes, thus increasing their resistance to shear thinning. FTIR analysis suggested the absence of covalent binding between CES and CEP. SEM showed a more homogeneous and dense gel structure, particularly in the CES-1.0%CEP sample. During in vitro digestion, the content of resistant starch in the complexes increased after CEP was added. Analysis of the interaction forces showed that the CES-CEP complexes had stronger hydrogen bonding and electrostatic interaction. This study offers valuable insights into the potential applications of CEP in starch-based foods.

Anion Binding Interaction Enhances the Robustness of Iodide for High-Performance Perovskite Solar Cells.

Owing to the ionic bond nature of the Pb-I bond, the iodide at the interface of perovskite polycrystalline films was easily lost during the preparation process, resulting in the formation of a large number of iodine vacancy defects. The presence of iodine vacancy defects can cause nonradiative recombination, provide a pathway for iodide migration, and be harmful to the power conversion efficiency (PCE) and stability of organic-inorganic hybrid perovskite solar cells (HPSCs). Here, in order to increase the robustness of iodides at the interface, a strategy to introduce anion binding effects was developed to stabilize the perovskite films. It was demonstrated that the N,N'-diphenylurea (DPU), characterized by high anionic binding constants and a Y-shaped structure, provides a relatively strong hydrogen bond donor site to effectively reduce the iodine loss during film preparation and inhibits iodide migration in the device working condition. As expected, the reduced iodine loss considerably improves the quality of the perovskite films and suppresses nonradiative recombination. The performance of the device after DPU modification was significantly increased, with the PCE rising from 23.65 to 25.01% with huge stability enhancement as well.

Influence of F-Containing Materials on Perovskite Solar Cells.

Perovskite solar cells (PSCs) are usually modified and passivated to improve their performance and stability. The interface modification and bulk doping are the two basic strategies. Fluorine (F)-containing materials are highly favored because of their unique hydrophobicity and coordination ability. This review discusses the basic characteristics of F, and the basic principles of improving the photovoltaic performance and stability of PSC devices using F-containing materials. We systematically summarized the latest progress in the application of F-containing materials to achieve efficient and stable PSCs on several key interface layers. It is believed that this work will afford significant understanding and inspirations toward the future application directions of F-containing materials in PSCs, and provide profound insights for the development of efficient and stable PSCs.

Correlation of MRI quantitative perfusion parameters with EGFR, VEGF and EGFR gene mutations in non-small cell cancer.

To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans, Kep, Ve, Vp, Fp) were obtained by Omni Kinetics software. Immunohistochemistry staining was used in the detection of the expression of VEGF and EGFR protein, and the mutation of EGFR gene was detected by PCR. Corresponding statistical test was performed to compare the parameters and protein expression between squamous cell carcinoma (SCC) and adenocarcinoma (AC), as well as EGFR mutations and wild-type. Correlation analysis was used to evaluate the correlation between parameters with the expression of VEGF and EGFR protein. Fp (skewness, kurtosis, energy) were statistically significant between SCC and AC, and the area under the ROC curve were 0.733, 0.700 and 0.675, respectively. The expression of VEGF in AC was higher than in SCC. Fp (skewness, kurtosis, energy) were negatively correlated with VEGF (r = - 0.527, - 0.428, - 0.342); Ktrans (Q50) was positively correlated with VEGF (r = 0.32); Kep (energy), Ktrans (skewness, kurtosis) were positively correlated with EGFR (r = 0.622, r = 0.375, 0.358), some histogram parameters of Kep, Ktrans (uniformity, entropy) and Ve (kurtosis) were negatively correlated with EGFR (r = - 0.312 to - 0.644). Some perfusion histogram parameters were statistically significant between EGFR mutations and wild-type, they were higher in wild-type than mutated (P < 0.05). Quantitative perfusion histogram parameters of DCE-MRI have a certain value in the differential diagnosis of NSCLC, which have the potential to non-invasively evaluate the expression of cell signaling pathway-related protein.

Associations between Paternal Obesity and Cardiometabolic Alterations in Offspring via Assisted Reproductive Technology.

CONTEXT: Both assisted reproductive technology (ART) and obesity are associated with adverse cardiometabolic alterations in offspring. However, the combined effects of paternal obesity and ART on offspring cardiometabolic health are still unclear. OBJECTIVE: To clarify cardiometabolic changes in offspring of obese fathers conceived using ART. DESIGN: Retrospective cohort study conducted between June 2014 and October 2019. SETTING: Center for reproductive medicine. PATIENTS: A total of 2890 singleton visits aged 4-10 years were followed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age-and sex-specific z-score of body mass index(BMI), blood pressure, insulin resistance and lipid profile were examined. RESULTS: We observed a strong association between paternal BMI categories and offspring BMI, blood pressure, and insulin resistance. Compared to offspring of fathers with normal weight, multivariable-adjusted mean difference for BMI z-score were 0.53 (95%CI: 0.37-0.68) for obese fathers, 0.17 (95%CI: 0.05-0.30) for overweight fathers, and -0.55 (95%CI: -0.95--0.15) for underweight fathers; corresponding values for systolic blood pressure z-score were 0.21(95%CI: 0.07-0.35), 0.10 (95%CI: -0.01-0.21), and -0.24 (95%CI: -0.59-0.11), and corresponding values for HOMA-IR z-score were 0.31(95%CI: 0.16-0.46), 0.09(95%CI: -0.02-0.21), and -0.11 (95%CI: -0.48-0.28), respectively. The mediation analyses suggested that 57.48% to 94.75% of the associations among paternal obesity and offspring cardiometabolic alterations might be mediated by offspring BMI. CONCLUSIONS: Paternal obesity was associated with an unfavourable cardiometabolic profile in ART-conceived offspring. Mediation analyses indicated that offspring BMI was a possible mediator of the association between paternal obesity and the offspring impaired metabolic changes.

DRAK2 suppresses autophagy by phosphorylating ULK1 at Ser56 to diminish pancreatic ß cell function upon overnutrition.

Impeded autophagy can impair pancreatic ß cell function by causing apoptosis, of which DAP-related apoptosis-inducing kinase-2 (DRAK2) is a critical regulator. Here, we identified a marked up-regulation of DRAK2 in pancreatic tissue across humans, macaques, and mice with type 2 diabetes (T2D). Further studies in mice showed that conditional knockout (cKO) of DRAK2 in pancreatic ß cells protected ß cell function against high-fat diet feeding along with sustained autophagy and mitochondrial function. Phosphoproteome analysis in isolated mouse primary islets revealed that DRAK2 directly phosphorylated unc-51-like autophagy activating kinase 1 (ULK1) at Ser56, which was subsequently found to induce ULK1 ubiquitylation and suppress autophagy. ULK1-S56A mutation or pharmacological inhibition of DRAK2 preserved mitochondrial function and insulin secretion against lipotoxicity in mouse primary islets, Min6 cells, or INS-1E cells. In conclusion, these findings together indicate an indispensable role of the DRAK2-ULK1 axis in pancreatic ß cells upon metabolic challenge, which offers a potential target to protect ß cell function in T2D.

Enhanced Quasi-Fermi Level Splitting of Perovskite Solar Cells by Universal Dual-Functional Polymer.

Perovskite solar cells (PSCs) have attracted extensive attention due to their higher power conversion efficiency (PCE) and simple fabrication process. However, the open-circuit voltage (VOC) loss remains a significant impediment to enhance device performance. Here, a facile strategy to boost the VOC to 95.5% of the Shockley-Queisser (S-Q) limit through the introduction of a universal multifunctional polymer additive is demonstrated. This additive effectively passivates the cation and anion defects simultaneously, thereby leading to the transformation from the strong n-type to weak n-type of perovskite films. Benefitting from the energy level alignment and the suppression of bulk non-radiative recombination, the quasi-Fermi level splitting (QFLS) is enhanced.  Consequently, the champion devices with 1.59 eV-based perovskite reach the highest VOC value of 1.24 V and a PCE of 23.86%. Furthermore, this strategy boosts the VOC by at least 0.07 V across five different perovskite systems, a PCE of 25.04% is achieved for 1.57 eV-based PSCs, and the corresponding module (14 cm2) also obtained a high PCE of 21.95%. This work provides an effective and universal strategy to promote the VOC approach to the detailed balance theoretical limit.

Involvement of CONSTANS-like Proteins in Plant Flowering and Abiotic Stress Response.

The process of flowering in plants is a pivotal stage in their life cycle, and the CONSTANS-like (COL) protein family, known for its photoperiod sensing ability, plays a crucial role in regulating plant flowering. Over the past two decades, homologous genes of COL have been identified in various plant species, leading to significant advancements in comprehending their involvement in the flowering pathway and response to abiotic stress. This article presents novel research progress on the structural aspects of COL proteins and their regulatory patterns within transcription complexes. Additionally, we reviewed recent information about their participation in flowering and abiotic stress response, aiming to provide a more comprehensive understanding of the functions of COL proteins.

Understanding the Role of Fluorine Groups in Passivating Defects for Perovskite Solar Cells.

Introducing fluorine (F) groups into a passivator plays an important role in enhancing the defect passivation effect for the perovskite film, which is usually attributed to the direct interaction of F and defect states. However, the interaction between electronegative F and electron-rich passivation groups in the same molecule, which may influence the passivation effect, is ignored. We herein report that such interactions can vary the electron cloud distribution around the passivation groups and thus changing their coordination with defect sites. By comparing two fluorinated molecules, heptafluorobutylamine (HFBM) and heptafluorobutyric acid (HFBA), we find that the F/-NH2 interaction in HFBM is stronger than the F/-COOH one in HFBA, inducing weaker passivation ability of HFBM than HFBA. Accordingly, HFBA-based perovskite solar cells (PSCs) provide an efficiency of 24.70 % with excellent long-term stability. Moreover, the efficiency of a large-area perovskite module (14.0 cm2 ) based on HFBA reaches 21.13 %. Our work offers an insight into understanding an unaware role of the F group in impacting the passivation effect for the perovskite film.

Luteolin Protects Pancreatic ß Cells against Apoptosis through Regulation of Autophagy and ROS Clearance.

Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (ß) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating ß cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of ß cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of ß cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in ß cells, possibly improving ß cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of ß cells. We also reveal some of the underlying mechanisms of luteolin's cytoprotective function.

Dietary Effects on Monocyte Phenotypes in Subjects With Hypertriglyceridemia and Metabolic Syndrome.

In patients with hypertriglyceridemia, a short-term low-saturated fat vs high-saturated fat diet induced lower plasma lipids and improved monocyte phenotypes. These findings highlight the role of diet fat content and composition for monocyte phenotypes and possibly cardiovascular disease risk in these patients. (Effects of Dietary Interventions on Monocytes in Metabolic Syndrome; NCT03591588).

Pretherapy investigations using highly robust visualized biomarkers from CT imaging by multiple machine-learning techniques toward its prognosis prediction for ALK-inhibitor therapy in NSCLC: a feasibility study.

PURPOSE: Molecularly targeted therapy has revolutionized the therapeutic landscape and is emerging as the first-line treatment option for ALK-rearranged non-small-cell lung cancer (NSCLC). In this study, the highly informative and robust biomarkers based on pre-treatment CT images and clinicopathologic features will be developed and validated to predict the prognosis for ALK-inhibitor therapy in NSCLC patients. METHODS: A total of 161 ALK-positive NSCLC patients treated with ALK inhibitors were retrospectively collected as training, validation and test sets from multi-center institutions. Cox proportional hazard regression (CPH) penalized by LASSO and random survival forest (RSF) coupled with recursive feature elimination (RFE) were used for radiomics and clinical features identification and model construction. An overlapping post-processing method was extra added to training process to investigate the stronger biomarker on the whole set. RESULTS: 123 of the collected cases progressed after a median follow-up of 15.5 months (IQR, 8.3-25.3). The T and M staging, pericardial effusion, age and ALK inhibitor-alectinib were determined as significant predictors in the survival analysis. Furthermore, we visualized the finally retained 4 radiomics feature. The RSF models built from overlapping-processed clinical and radiomics features respectively reached the maximum C-index of 0.68 and 0.75,but the combination of them,radioclinical signature, improved the score to 0.78. The model on the validation and external test datasets yielded the C-index of 0.73 and 0.79, with the iAUC of 0.76 and 0.83, the IBS of 0.119 and 0.112. CONCLUSION: With respect to a simple selection strategy of overlapping optimal radiomics and clinical features from different survival models may promote better progression-free survival(PFS) prediction than conventional survival analysis, which provides a potential method for guiding personalized pre-treatment options of NSCLC.

Polymerization Strategies to Construct a 3D Polymer Passivation Network toward High Performance Perovskite Solar Cells.

The spontaneously formed uncoordinated Pb2+ defects usually make the perovskite films demonstrate strong n-type with relatively lower carrier diffusion length and serious non-radiative recombination energy loss. In this work, we adopt different polymerization strategies to construct three-dimensional passivation frameworks in the perovskite layer. Thanks to the strong C≡N⋅⋅⋅Pb coordination bonding and the penetrating passivation structure, the defect state density is obviously reduced, accompanied by a significant increase in the carrier diffusion length. Additionally, the reduction of iodine vacancies also changed the Fermi level of the perovskite layer from strong n-type to weak n-type, which substantially promotes the energy level alignment and carrier injection efficiency. As a result, the optimized device achieved an efficiency exceeded 24 % (the certified efficiency is 24.16 %) with a high open-circuit voltage of 1.194 V, and the corresponding module achieved an efficiency of 21.55 %.