The key role of myostatin b in somatic growth in fishes derived from distant hybridization.

The basic mechanism of heterosis has not been systematically and completely characterized. In previous studies, we obtained three economically important fishes that exhibit rapid growth, WR (WCC ♀ × RCC ♂), WR-II (WR ♀ × WCC ♂), and WR-III (WR-II ♀ × 4nAU ♂), through distant hybridization. However, the mechanism underlying this rapid growth remains unclear. In this study, we found that WR, WR-II, and WR-III showed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species (RCC and WCC). Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes. Notably, the mRNA level of mstnb (myostatin b), which is a negative regulator of myogenesis, was significantly reduced in WR, WR-II, and WR-III compared with the parent species. To verify the function of mstnb, a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique. The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57% compared with that in wild-type siblings. Moreover, the area and number of muscle fibers were significantly increased in mstnb-deficient RCC, indicating hypertrophy and hyperplasia. Furthermore, the muscle protein and fat contents were significantly increased in mstnb-deficient RCC. The molecular regulatory mechanism of mstnb was then revealed by transcription profiling, which showed that genes related to myogenesis (myod, myog, and myf5), protein synthesis (PI3K-AKT-mTOR), and lipogenesis (pparγ and fabp3) were highly activated in hybrid fishes and mstnb-deficient RCC. This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis, protein synthesis, and lipogenesis in hybrid fishes and mstnb-deficient RCC, which provides evidence for the molecular mechanism of heterosis via distant hybridization.

Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments.

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational "triple treatments" to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm-1 K-2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 µW cm-2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Paxillin phase separation promotes focal adhesion assembly and integrin signaling.

Focal adhesions (FAs) are transmembrane protein assemblies mediating cell-matrix connection. Although protein liquid-liquid phase separation (LLPS) has been tied to the organization and dynamics of FAs, the underlying mechanisms remain unclear. Here, we experimentally tune the LLPS of PXN/Paxillin, an essential scaffold protein of FAs, by utilizing a light-inducible Cry2 system in different cell types. In addition to nucleating FA components, light-triggered PXN LLPS potently activates integrin signaling and subsequently accelerates cell spreading. In contrast to the homotypic interaction-driven LLPS of PXN in vitro, PXN condensates in cells are associated with the plasma membrane and modulated by actomyosin contraction and client proteins of FAs. Interestingly, non-specific weak intermolecular interactions synergize with specific molecular interactions to mediate the multicomponent condensation of PXN and are efficient in promoting FA assembly and integrin signaling. Thus, our data establish an active role of the PXN phase transition into a condensed membrane-associated compartment in promoting the assembly/maturation of FAs.

Formation of Different Polyploids Through Disrupting Meiotic Crossover Frequencies Based on cntd1 Knockout in Zebrafish.

Polyploidy, a significant catalyst for speciation and evolutionary processes in both plant and animal kingdoms, has been recognized for a long time. However, the exact molecular mechanism that leads to polyploid formation, especially in vertebrates, is not fully understood. Our study aimed to elucidate this phenomenon using the zebrafish model. We successfully achieved an effective knockout of the cyclin N-terminal domain containing 1 (cntd1) using CRISPR/Cas9 technology. This resulted in impaired formation of meiotic crossovers, leading to cell-cycle arrest during meiotic metaphase and triggering apoptosis of spermatocytes in the testes. Despite these defects, the mutant (cntd1-/-) males were still able to produce a limited amount of sperm with normal ploidy and function. Interestingly, in the mutant females, it was the ploidy not the capacity of egg production that was altered. This resulted in the production of haploid, aneuploid, and unreduced gametes. This alteration enabled us to successfully obtain triploid and tetraploid zebrafish from cntd1-/- and cntd1-/-/- females, respectively. Furthermore, the tetraploid-heterozygous zebrafish produced reduced-diploid gametes and yielded all-triploid or all-tetraploid offspring when crossed with wild-type (WT) or tetraploid zebrafish, respectively. Collectively, our findings provide direct evidence supporting the crucial role of meiotic crossover defects in the process of polyploidization. This is particularly evident in the generation of unreduced eggs in fish and, potentially, other vertebrate species.

Interrupted N-Heterocyclic Carbene-Catalyzed Radical Coupling Strategy: A Versatile Platform for Alkylation and Arylation of [60]Fullerene.

An interrupted N-heterocyclic carbene-catalyzed radical coupling strategy is disclosed for efficient alkylation and arylation of [60]fullerene. This novel and general strategy bridges the gap between organocatalytic radical cross-coupling and functionalization of fullerenes. Readily available feedstocks, remarkably broad substrate scope and functional group compatibility, and convenient late-stage nanomodification of complex molecules make this strategy with incomparable diversity and practicality in the synthesis of monoalkylated and -arylated fullerenes.

Decoupling Carrier-Phonon Scattering Boosts the Thermoelectric Performance of n-Type GeTe-Based Materials.

The coupled relationship between carrier and phonon scattering severely limits the thermoelectric performance of n-type GeTe materials. Here, we provide an efficient strategy to enlarge grains and induce vacancy clusters for decoupling carrier-phonon scattering through the annealing optimization of n-type GeTe-based materials. Specifically, boundary migration is used to enlarge grains by optimizing the annealing time, while vacancy clusters are induced through the aggregation of Ge vacancies during annealing. Such enlarged grains can weaken carrier scattering, while vacancy clusters can strengthen phonon scattering, leading to decoupled carrier-phonon scattering. As a result, a ratio between carrier mobility and lattice thermal conductivity of ∼492.8 cm3 V-1 s-1 W-1 K and a peak ZT of ∼0.4 at 473 K are achieved in Ge0.67Pb0.13Bi0.2Te. This work reveals the critical roles of enlarged grains and induced vacancy clusters in decoupling carrier-phonon scattering and demonstrates the viability of fabricating high-performance n-type GeTe materials via annealing optimization.

MicroRNA-196a-5p facilitates the onset and progression via targeting ITM2B in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy affecting the digestive tract, with an increasing incidence rate worldwide. Recently, numerous studies revealed that microRNAs were associated with gene expression regulation, particularly their involvement in the regulation of tumor cells, garnering widespread attention. Here, we discovered that miR-196a-5p was significantly upregulated in both ESCC tissues and cells, which was correlated with an unfavorable prognosis. Series functional in vitro investigations have confirmed that silencing miR-196a-5p obviously restrained the ESCC cells malignant phenotypes and promoted apoptosis. Bioinformatics analysis and rescue experiments revealed that miR-196a-5p directly targeted ITM2B, exerting influence on the development of ESCC cells through negative regulation of ITM2B expression. Xenograft mouse models were established for conducting in vivo experiments, providing further confirmation of the regulatory mechanism and biological significance of the miR-196a-5p/ITM2B axis in ESCC. Our research demonstrated miR-196a-5p promoted ESCC malignant progression by interacting with ITM2B, thereby providing novel clues and potential targets for the new diagnosis and thereby of ESCC.

Evolutionarily conserved IL-22 participates in gut mucosal barrier through its receptors IL-22BP, IL-10R2 and IL-22RA1 during bacterial infection in teleost.

IL-22 is a critical cytokine of epithelial mucosal barrier. In humans, IL-22 signals through a heteroduplex receptor consisting of IL-22R and IL-10Rß. In fish, IL-22 and its receptors homologues have been cloned in a number of species, however, no studies have been reported how the receptors are involved in IL-22 transduction. For this purpose, in this study we identified IL-22 and its soluble receptor IL-22BP and transmembrane receptors IL-22RA1 and IL-10R2 in Carassius cuvieri × Carassius auratus red var. (named WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1, respectively). WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1 were relatively conserved in the evolutionary process, sharing the same conserved domains as their higher vertebrate homologues. When the fish were infected with the Aeromonas hydrophila, the expression of WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1 were significantly induced in the gut. The co-IP assay showed that WR-IL-22 not only interacted with WR-IL-22BP, but also with WR-IL10R2 and WR-IL22RA1. When introduced in vivo, WR-IL-22 activated the JAK1-STAT3 axis and protected the gut mucosa from A. hydrophila infection. However, overexpression of WR-IL-22BP or knockdown of transmembrane receptors WR-IL10R2 and WR-IL22RA1 significantly inhibited the activation of WR-IL-22-mediated JAK1-STAT3 axis and promoted bacterial colonization in the gut. These results provided new insights into the role of IL-22 and its receptors in the gut mucosa barrier and immune response in teleost.

Distribution and transformation of potentially toxic elements in crack under coal mining disturbance.

In China, coal provides about 56.8% of the energy. Most of China's coal mines are shaft mines, which cause the surface to collapse and crack during the mining process. The soil near the cracks changes its physicochemical properties due to the altered stress conditions. This will affect the distribution of PTEs in the soil. We collected 18 samples from a selected crack in the abandoned land. The pH, Eh, and PTE and their fractions of the samples were determined. With the test results, we understand the distribution characteristics of pH, Eh, PTEs, and their fractions at the cracks. Meanwhile, we explored the key factors that contribute to this distribution. It was determined that crack decreases surface soil pH while increasing Eh. The total amount of 7 PTEs is higher in the bottom soil of the main crack and 2 m away from the main crack. The content of reducible fractions of PTEs increases with the increase of soil Eh. The oxidizable and residual fractions of PTEs adsorbed to the clay particles migrate to and enrich the deeper layers of the main crack. This study emphasizes the effect of crack generation on the distribution of PTEs in soil. It provides insights to describe the distribution of PTE throughout the full life cycle of crack.

Synthesis and Performance Testing of Maleic Anhydride-Ene Monomers Multicomponent Co-Polymers as Pour Point Depressant for Crude Oil.

To address the issue of pipeline blockage caused by the formation of waxy deposits inside pipelines, hindering the flow of petroleum in the Shengli oilfield, eight new-style polyacrylic acid pour point depressants (PPD) for Shengli crude oil were prepared by maleic anhydride and ene monomers with different polar and aromatic pendant chains. The synthesized Pour Point Depressants were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and polarizing optical microscopy (POM). The results were promising and demonstrated that any type of pour point depressant exhibited excellent performance on high-pour-point crude oil. The reduction in pour-point after additive addition was largely dependent on the polymer structure. Notably, polymers containing long alkyl side chains and aromatic units displayed the most impressive performance, capable of depressing the pour point by 12 °C.

Radioimmunotherapy Targeting B7-H3 in situ glioma models enhanced antitumor efficacy by Reconstructing the tumor microenvironment.

Radionuclide drug conjugates (RDCs) with antibodies serve as a novel approach for the treatment of malignant tumors including glioblastoma. However, RDCs require optimal antibodies to work efficiently. Hu4G4, a novel B7-H3-targeting humanized monoclonal IgG1 antibody, is highly specific for the human B7-H3 protein (a marker of tumor cells, including glioblastoma cells). Herein, we established 131I-labeled hu4G4 (131I-hu4G4) and showed that it specifically bound to B7-H3 with high affinity (Kd = 0.99 ± 0.07 nM) and inhibited the growth of U87 cells in vitro. 131I-hu4G4 displayed potent in situ antitumor activity in a mouse model of glioma based on GL261 Red-Fluc-B7-H3 cells. More importantly, 131I-hu4G4 remodeled the tumor microenvironment and promoted the transformation of glioma from "cold" to "hot" tumors by promoting CD4+ and CD8+ T cell infiltration and the polarization of M2 to M1. Therefore, the antitumor activity observed with 131I-hu4G4, together with its ability to enhance antitumor immune responses, makes it a novel candidate for radioimmunotherapy of glioblastoma.

Anion Cascade Reactions. Part I: Synthesis of 3-Isoquinuclidones from a Nazarov-like Reagent.

A simple and atom-economical one-step protocol is described for the synthesis of biologically valuable 3-isoquinuclidones. The method proceeds from the simple starting materials, α-acyl N-arylcinnamamides, and can be performed under mild conditions in the presence of tBuOK. The key steps of this process are the double Michael addition reaction of a Nazarov-like reagent and the subsequent intramolecular hemiamination. These flexible intermolecular reactions could be performed on a gram scale.

Palladium-catalyzed intramolecular aza-Wacker-type cyclization of vinyl cyclopropanecarboxamides to access conformationally restricted aza[3.1.0]bicycles.

A palladium(ii)-catalyzed intramolecular oxidative aza-Wacker-type reaction of vinyl cyclopropanecarboxamides to access a series of conformationally restricted highly substituted aza[3.1.0]bicycles is reported. The transformation proceeded through a typical aza-Wacker reaction mechanism to forge a new C-N bond with oxygen as the terminal oxidant. The desired fused heterocycles were obtained in moderate yields. The process is tolerant of a range of functional aryl groups under mild conditions.

Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners.

The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)n sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)n have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)n have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA-protein interactions or impeding the phase transition of r(GGGGCC)n. In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)n, its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)n and its influence on partner binding. Given the crucial role of r(GGGGCC)n in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)n RNA.

Uterus-preserving surgical management of placenta accreta spectrum disorder: a large retrospective study.

BACKGROUND: The two-child policy implemented in China resulted in a surge of high-risk pregnancies among advanced maternal aged women and presented a window of opportunity to identify a large number of placenta accreta spectrum (PAS) cases, which often invoke severe blood loss and hysterectomy. We thus had an opportunity to evaluate the surgical outcomes of a unique conservative PAS management strategy for uterus preservation, and the impacts of magnetic resonance imaging (MRI) in PAS surgical planning. METHODS: Cross-sectional study, comparing the outcomes of a new uterine artery ligation combined with clover suturing technique (UAL + CST) with the existing conservative surgical approaches in a maternal public hospital with an annual birth of more than 20,000 neonates among all placenta previa cases suspecting of PAS between January 1, 2015 and December 31, 2018. RESULTS: From a total of 89,397 live births, we identified 210 PAS cases from 400 singleton pregnancies with placenta previa. Aside from 2 self-requested natural births (low-lying placenta), all PAS cases had safe cesarean deliveries without any total hysterectomy. Compared with the existing approaches, the evaluated UAL + CST had a significant reduction in intraoperative blood loss (ß=-312 ml, P < .001), RBC transfusion (ß=-1.08 unit, P = .001), but required more surgery time (ß = 16.43 min, P = .01). MRI-measured placenta thickness, when above 50 mm, can increase blood loss (ß = 315 ml, P = .01), RBC transfusion (ß = 1.28 unit, P = .01), surgery time (ß = 48.84 min, P < .001) and hospital stay (ß = 2.58 day, P < .001). A majority of percreta patients resumed normal menstrual cycle within 12 months with normal menstrual fluid volume, without abnormal urination or defecation. CONCLUSIONS: A conservative surgical management approach of UAL + CST for PAS is safe and effective with a low complication rate. MRI might be useful for planning PAS surgery. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000035202.

Mechanism of morusin on breast cancer via network pharmacology and in vitro experiments.

BACKGROUND: This study aimed to investigate the therapeutic effect of morusin on breast cancer and decode its underlying molecular mechanism using network pharmacology and in vitro techniques. METHODS: Swiss Target Prediction and PharMmapper were applied to screen morusin targets. The targets of human breast cancer were obtained from the GeneCards database, and the overlapping targets were screened. A protein-protein interaction network was constructed based on the overlapping targets by String and Cytoscape. Performed Gene Ontology enrichment as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the shared targets of the drug and disease using the David database. Additionally, performed molecular docking using PyMoL and AutoDock software. Finally, the impact of morusin on breast cancer was demonstrated by cell experiments and western blot. RESULTS: A total of 101 target genes were obtained through screening including ESR1, EGFR, ALB, CTNNB1, AKT1, and so on. Based on the annotation of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, the anticancer properties of morusin are linked to apoptosis, migration, and PI3K-AKT signaling pathways. Molecular docking showed an interaction between morusin and PIK3CA, AKT1. In vitro data demonstrated that morusin causes apoptosis and inhibits cell migration. Morusin also increased the expression of cleaved-PARP while decreasing the expression of p-PI3K and p-AKT. CONCLUSION: Through network pharmacology analysis and in vitro experiments, this study showed that morusin promotes apoptosis and inhibits migration by modulating the PI3K-AKT axis. Morusin plays a key role in the treatment of breast cancer.

Ultrafast and Cost-Effective Fabrication of High-Performance Carbon-Based Flexible Thermoelectric Hybrid Films and Their Devices.

Due to their cost-effectiveness and industry-scale feasibility, carbon-based composites have been considered to be promising thermoelectric materials for low-grade power generation. However, current fabrications for carbon-based composites are time-consuming, and their thermoelectric properties are still low. Herein, we develop an ultrafast and cost-effective hot-pressing method to fabricate a novel carbon-based hybrid film, which consists of ionic liquid/phenolic resin/carbon fiber/expanded graphite. This method only costs no more than 15 min. We found that the expanded graphite as the major component enables high flexibility and the introduction of phenolic resin and carbon fiber enhances the shear resistance and toughness of the film, while the ion-induced carrier migration contributes to a high power factor of 38.7 µW m-1 K-2 at 500 K in the carbon-based hybrid film. After the comparison based on the ratios between the power factor with fabrication time and cost among the current conventional carbon-based thermoelectric composites, our hybrid films show the best cost-effective property. Besides, a flexible thermoelectric device, assembled by the as-designed hybrid films, shows a maximum output power density of 79.3 nW cm-2 at a temperature difference of 20 K. This work paves a new way to fabricate cost-effective and high-performance carbon-based thermoelectric hybrids with promising application potential.

Ultralow Lattice Thermal Conductivity and High Thermoelectric Performance in Ge1-x-yBixCayTe with Ultrafine Ferroelectric Domain Structure.

GeTe and its derivatives emerging as a promising lead-free thermoelectric candidate have received extensive attention. Here, a new route was proposed that the minimization of κL in GeTe through considerable enhancement of acoustic phonon scattering by introducing ultrafine ferroelectric domain structure. We found that Bi and Ca dopants induce strong atomic strain disturbance in the GeTe matrix because of large differences in atom radius with host elements, leading to the formation of ultrafine ferroelectric domain structure. Furthermore, large strain field and mass fluctuation induced by Bi and Ca codoping result in further reduced κL by effectively shortening the phonon relaxation time. The co-existence of ultrafine ferroelectric domain structure, large strain field, and mass fluctuation contribute to an ultralow lattice thermal conductivity of 0.48 W m-1 K-1 at 823 K. Bi and Ca codoping significantly enhances the Seebeck coefficient and power factor through reducing the energy offset between light and heavy valence bands of GeTe. The modified band structure boosts the power factor up to 47 µW cm-1 K-2 in Ge0.85Bi0.09Ca0.06Te. Ultimately, a high ZT of ∼2.2 can be attained. This work demonstrates a new design paradigm for developing high-performance thermoelectric materials.

Dosimetric and clinical analysis of pseudo-progression versus recurrence after hypo-fractionated radiotherapy for brain metastases.

BACKGROUND: The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. METHODS: The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P < 0.05 and associated with recurrence were used to establish a nomogram prediction model and validated by Bootstrap repeated sampling, which was validated in an internal cohort (n = 23) from October 2019 to December 2021. RESULTS: The median follow-up time was 68.4 months (range, 8.9-146.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to pseudo-progression and tumor recurrence were 18.3 months (quartile range, 9.4-27.8 months) and 12.9 months (quartile range, 8.7-19.6 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve values were 0.730 and 0.967 in the training and validation cohorts, respectively. Thirty-one patients received salvage therapy in the tumor recurrence group. The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI 56.8-75.9 months) and 39.6 months (95% CI 29.2-50.0 months, respectively; P = 0.001). CONCLUSIONS: Clinical and dosimetry features of hypo-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hypo-fractionated radiotherapy for brain metastases. Gross tumor volume, biological effective dose, target coverage, and having received targeted therapy or not were factors associated with the occurrence of tumor recurrence, and the individual risk could be estimated by the nomogram effectively.