Influence of different hydrocolloids on the pasting, rheological, and morphological characteristics of heat gelatinized cassava starch.

Heat-gelatinized starch (HGS), which is prepared via heat treatment, enhances viscosity and provides suitable thickening properties, which improve water retention in products. This study aimed to investigate the potential of blending gelatinized starch with edible hydrocolloids (guar gum, carrageenan (C), locust bean gum, konjac powder, and sodium alginate) to assess their effect on the stabilization of starch gelatinization and reduction of retrogradation. Optical microscopic observations revealed the disrupted structures of gelatinized starch after heat treatments, along with diminished or absent birefringence. Adding C to the gelatinized starch reduced its peak viscosity, breakdown and setback value. For the rheological analysis, heat gelatinization and hydrocolloid addition contributed to the increased elasticity and viscosity of samples. Gelatinization and hydrocolloid addition emerged as effective strategies for improving starch quality. Although it still warrants further exploration, the introduced approach holds potential for applications in the development of convenience and canned food products.

Difficulty-Guided Variant Degradation Learning for Blind Image Super-Resolution.

Recent blind super-resolution (BSR) methods are explored to handle unknown degradations and achieve impressive performance. However, the prevailing assumption in most BSR methods is the spatial invariance of degradation kernels across the entire image, which leads to significant performance declines when faced with spatially variant degradations caused by object motion or defocusing. Additionally, these methods do not account for the human visual system's tendency to focus differently on areas of varying perceptual difficulty, as they uniformly process each pixel during reconstruction. To cope with these issues, we propose a difficulty-guided variant degradation learning network for BSR, named difficulty-guided degradation learning (DDL)-BSR, which explores the relationship between reconstruction difficulty and degradation estimation. Accordingly, the proposed DDL-BSR consists of three customized networks: reconstruction difficulty prediction (RDP), space-variant degradation estimation (SDE), and degradation and difficulty-informed reconstruction (DDR). Specifically, RDP learns the reconstruction difficulty with the proposed reconstruction-distance supervision. Then, SDE is designed to estimate space-variant degradation kernels according to the difficulty map. Finally, both degradation kernels and reconstruction difficulty are fed into DDR, which takes into account such two prior knowledge information to guide super-resolution (SR). Experimental analysis on various synthetic datasets demonstrates that DDL-BSR invariably surpasses state-of-the-art (SOTA) methods, producing SR images with enhanced realism and texture quality. Code is available at https://github.com/JiaWang0704/DDL-BSR.

Association Between the Aggregate Index of Systemic Inflammation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Retrospective Study.

Purpose: The Aggregate Index of Systemic Inflammation (AISI) has emerged as a novel marker for inflammation and prognosis, but its role in patients with acute myocardial infarction has not been studied. Therefore, this study aimed to investigate the impact of different AISI levels on the clinical outcomes of patients with acute myocardial infarction. Patients and Methods: This study was a retrospective study, including 1044 patients with acute myocardial infarction (AMI) who were treated at the Fujian Medical University Affiliated Union Hospital, China from May 2017 to December 2022. The patients were divided into high and low AISI groups based on the median value (Q1 Group, ≤ 416.15, n=522; Q2 Group, ≥ 416.16, n=522), and the differences in baseline characteristics and clinical outcomes between the two groups were analyzed. The primary outcome included major adverse cardiovascular and cerebrovascular events (MACCEs), while the secondary outcomes included contrast-induced nephropathy (CIN) risk and all-cause rehospitalization rate. Results: The findings of the single-factor analysis suggest that a significant association between high AISI levels and the occurrence of MACCEs in AMI patients. After adjusting for confounding factors, the results indicated that compared to Q1, patients in the Q2 group had a higher risk of all-cause mortality [adjusted odds ratio (aOR) 4.64; 95% CI 1.37-15.72; p=0.032], new-onset atrial fibrillation (aOR 1.75; 95% CI 1.02-3.00; p=0.047), and CIN (aOR 1.75; 95% CI 1.02-3.01; p=0.043), with all differences being statistically significant. Conclusion: In the population of AMI patients, an elevated AISI level is significantly associated with an increased risk of cardiovascular death and can serve as an early marker for adverse prognosis.

Survival benefit of adjuvant TACE for patients with hepatocellular carcinoma and child-pugh B7 or B8 after hepatectomy.

BACKGROUND & AIMS: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. METHODS: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). RESULTS: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. CONCLUSION: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3ß/ß-catenin&ERK signaling.

BACKGROUND: The histone-lysine N-methyltransferase SMYD1, which is specific to striated muscle, plays a crucial role in regulating early heart development. Its deficiency has been linked to the occurrence of congenital heart disease. Nevertheless, the precise mechanism by which SMYD1 deficiency contributes to congenital heart disease remains unclear. METHODS: We established a SMYD1 knockout pluripotent stem cell line and a doxycycline-inducible SMYD1 expression pluripotent stem cell line to investigate the functions of SMYD1 utilizing an in vitro-directed myocardial differentiation model. RESULTS: Cardiomyocytes lacking SMYD1 displayed drastically diminished differentiation efficiency, concomitant with heightened proliferation capacity of cardiac progenitor cells during the early cardiac differentiation stage. These cellular phenotypes were confirmed through experiments inducing the re-expression of SMYD1. Transcriptome sequencing and small molecule inhibitor intervention suggested that the GSK3ß/ß-catenin&ERK signaling pathway was involved in the proliferation of cardiac progenitor cells. Chromatin immunoprecipitation demonstrated that SMYD1 acted as a transcriptional activator of GSK3ß through histone H3 lysine 4 trimethylation. Additionally, dual-luciferase analyses indicated that SMYD1 could interact with the promoter region of GSK3ß, thereby augmenting its transcriptional activity. Moreover, administering insulin and Insulin-like growth factor 1 can enhance the efficacy of myocardial differentiation in SMYD1 knockout cells. CONCLUSIONS: Our research indicated that the participation of SMYD1 in the GSK3ß/ß-catenin&ERK signaling cascade modulated the proliferation of cardiac progenitor cells during myocardial differentiation. This process was partly reliant on the transcription of GSK3ß. Our research provided a novel insight into the genetic modification effect of SMYD1 during early myocardial differentiation. The findings were essential to the molecular mechanism and potential interventions for congenital heart disease.

EB-SUN, a New Microtubule Plus-End Tracking Protein in Drosophila.

Microtubule (MT) regulation is essential for oocyte development. In Drosophila, MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins (MAPs) that regulate MTs in the Drosophila ovary, we identified a previously uncharacterized gene, CG18190, encoding a novel MT end-binding (EB) protein, which we propose to name EB-SUN. We show that EB-SUN colocalizes with EB1 at growing microtubule plus-ends in Drosophila S2 cells. Tissue-specific and developmental expression profiles from Paralog Explorer reveal that EB-SUN is predominantly expressed in the ovary and early embryos, while EB1 is ubiquitously expressed. Furthermore, as early as oocyte determination, EB-SUN comets are highly concentrated in oocytes during oogenesis. EB-SUN knockout (KO) results in a decrease in MT density at the onset of mid-oogenesis (Stage 7) and delays oocyte growth during late mid-oogenesis (Stage 9). Combining EB-SUN KO with EB1 knockdown (KD) in germ cells significantly further reduced MT density at Stage 7. Notably, all eggs from EB-SUN KO/EB1 KD females fail to hatch, unlike single gene depletion, suggesting a functional redundancy between these two EB proteins during embryogenesis. Our findings indicate that EB-SUN and EB1 play distinct roles during early embryogenesis.

A comparative study on the efficacy between omega toenail correction and winograd procedure for stage II-III paronychia.

The objective of this study is to conduct a prospective trial comparing the therapeutic efficacy of Omega toenail correction and the Winograd procedure in treating stage II-III paronychia. From August 2018 to August 2023, ninety cases from eighty-three patients were randomly divided into two groups, one receiving Omega toenail correction (experimental group) and the other receiving the Winograd procedure (control group). The clinical therapeutic effects of both treatments were evaluated based on time to resume movement, treatment cycle, one-year recurrence rate, and visual analogue scale (VAS) scores before and after treatment. The clinical efficacy was compared between Omega toenail correction and Winograd procedure treating paronychia of stage Ⅱ-Ⅲ. It has been demonstrated that the time to resume movement in the experimental group is obviously shorter than that in the control group (P = 0.024), while the treatment cycle is longer (P = 0.009) with no significant difference (P = 0.734) in the aspect of one-year recurrence rate. However, the VAS after the correction in the experimental group is significantly lower than that in the control group (P = 0.019). It has been suggested that Omega toenail correction characterized by easy operation, sure efficacy and lower recurrence rate can be widely applied in clinic work.

Interfacial Thermal Fluctuations Stabilize Bulk Nanobubbles.

Consensus on bulk nanobubble stability remains elusive, despite accepted indirect evidence for longevity. We develop a nanobubble evolution model by incorporating thermal capillary wave theory that reveals that dense nanobubbles generated by acoustic cavitation tend to shrink and intensify interfacial thermal fluctuations; this significantly reduces surface tension to neutralize enhanced Laplace pressure, and secures their stabilization at a finite size. A stability criterion emerges: thermal fluctuation intensity scales superlinearly with curvature: sqrt[⟨h^{2}⟩]∝(1/R)^{n}, n>1. The model prolongs the time frame for nanobubble contraction to 2 orders of magnitude beyond classical theory estimates, and captures the equilibrium radius (90-215 nm) within the experimental range.

Current status and influencing factors of nurses' knowledge and attitudes towards clinical research ethical in China: a province-wide cross-sectional survey.

BACKGROUND: Nurses' competence in clinical research is a key element in promoting high quality in the discipline of nursing, and the ethical aspects of research are of paramount importance. Therefore, nurses need to have a comprehensive understanding of the ethics associated with clinical research, which is an integral part of safeguarding the safety of subjects, ensuring the quality of nursing clinical research, and improving the ethical standardization of clinical research. METHODS: A cross-sectional survey was conducted on 304 nurses in a province of China between April 2023 and September 2023, utilizing convenience sampling. The survey questionnaire comprised two sections: a general information form and a questionnaire focusing on nurses' knowledge and attitudes towards clinical research ethics. Data analysis encompassed descriptive statistics, t-tests, one-way ANOVA, and multiple linear regression. RESULTS: A total of 320 questionnaires were distributed, of which 304 were valid. The ethical attitude of nurses in clinical research was better (91.17 ± 15.96), while the cognitive score was lower (63.08 ± 12.30). The results of multiple linear regression analysis showed that degree, grade of hospital (I, II or III), technical title, number of clinical projects chaired in one year and whether the respondent has ever participated in an ethics training were the five factors influencing the knowledge of clinical research ethics (F = 9.341, P < 0.001, R2 = 18.0%); degree, grade of hospital (I, II or III), technical title, number of clinical research projects chaired in one year, whether the hospital has an ethics committee and whether the respondent has ever participated in an ethics training were the six factors affecting ethical attitudes towards clinical research (F = 8.919, P < 0.001, R2 = 17.3%). CONCLUSIONS: Nurses in a Chinese province scored low on the cognitive dimension of clinical research ethics, but their attitudes were at a relative high level, with many influencing factors. Degree, technical title, and grade of hospital, all affect cognitive and attitude scores. It is also worth noting that whether the hospital has an ethics committee affects the attitude scores, but has no effect on the cognitive scores.Nursing administrators and educators should consider providing effective and targeted strategies (e.g., ongoing training, scholarly seminars, and scholarly exchanges) to enhance nurses' knowledge and competence in clinical research ethics to protect subject rights as well as to ensure the quality of clinical research.

RhD-positive red blood cell allocation practice to RhD-negative patients before and during the COVID-19 pandemic.

OBJECTIVES: The red blood cell (RBC) D antigen is highly immunogenic, and anti-D alloimmunization can cause hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. This study examined how RhD-negative patients who required packed RBCs (pRBCs) were handled during the COVID-19 pandemic and whether policies and practices on RhD-positive pRBC allocation to RhD-negative patients changed. METHODS: The Association for the Advancement of Blood & Biotherapies (AABB) Clinical Hemotherapy Subsection distributed a 17-question survey to physician AABB members to elucidate the impact of the COVID-19 pandemic on the policies and practices governing the provision of RhD-positive pRBCs to RhD-negative patients. RESULTS: There were 215 respondents who started the survey, but only 104 answered all the questions. Most institutional policies (130/155 [83.87%]) and personal practices (100/126 [79.37%]) on pRBC selection did not change during the COVID-19 pandemic. The practice of switching back to RhD-negative pRBCs after administration of RhD-positive pRBCs is variable. More than half of respondents (56/104 [53.85%]) reported offering Rh immunoglobulin to any Rh-negative patients who received RhD-positive pRBCs. CONCLUSIONS: Despite RhD-negative pRBC supply challenges, most institutional policies and personal practices on when to provide RhD-positive pRBCs to RhD-negative patients did not change during the pandemic.

Exosomal CTHRC1 from cancer-associated fibroblasts facilitates endometrial cancer progression via ITGB3/FAK signaling pathway.

The emerging tumor microenvironment (TME) is a complex and constantly evolving entity. Cancer-associated fibroblasts (CAFs) are a vital component of the TME with diverse functions. They interact closely with cancer cells through reciprocal signaling and play a crucial role in tumor progression. Exosomes, which contain diverse biological information, are identified as an important mediator of cell-cell communication. This study aimed to investigate how CAF-derived exosomes promote metastasis of endometrial cancer (EC). Our findings revealed that CAF-derived exosomes significantly enhanced EC cell proliferation and migration compared to normal fibroblast-derived exosomes. Quantitative proteomics analysis of CAF/NF-derived exosomes demonstrated differential expression of CTHRC1, a protein overexpressed in multiple tumors, promoting cancer progression through enhanced cell migration and invasion. Exosomal overload of CTHRC1 significantly contributes to EC cell migration. Mechanically, we determined that ITGB3 was immunoprecipitated by CTHRC1 and phosphorylated FAK on Tyr397, which was important for exosomal CTHRC1 mediated migratory ability of EC cells. Overexpression of CTHRC1 in secreted exosomes promotes the metastatic ability of EC cells in mouse models and may be eliminated by Defactinib, an inhibitor of FAK Tyr397 phosphorylation. Moreover, overexpression of CTHRC1 was increased in EC patients, elevating with cancer progression, and correlated with negative tumor prognosis. Our results revealed that CAF mediated endometrial cancer progression is related to high levels of CTHRC1 and exosomal CTHRC1 derived from CAF may be a promising therapeutic strategy for metastatic endometrial cancer.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies.

BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.

Study on the metabolism of Xiao-Jian-Zhong-Tang in rats with chronic atrophic gastritis coupled with bioinformatics.

Xiao-Jian-Zhong-Tang (XJZT) has the effect of warming the middle and tonifying the deficiency, easing the urgency and relieving pain according to the theory of traditional Chinese medicine (TCM), and is able to treat spleen deficiency type chronic atrophic gastritis (CAG). Metabolites of TCM in cecum contents are common metabolites of intestinal bacteria and hosts, which can reflect the metabolic status in disease states. The present work was performed to study the effect of XJZT against CAG coupled with the cecal metabolites analysis and bioinformatics. A total of nine prototypical components and 144 metabolites were firstly identified in the cecum metabolites of XJZT using ultra-high performance liquid chromatography added to the quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS), which underwent the metabolism of oxidation, reduction, methylation, and glucuronic acid reaction Furthermore, different prototypical compounds might metabolize into identical metabolites in the presence of intestinal flora. Bioinformatics was further used to correlate these metabolites with the disease and intestinal flora. Components and targets were screened by Cytoscape, and molecular docking of key targets and core components showed good binding ability. This study provided important information for exploring the mechanism of TCM formulae.

"Mitotic" kinesin-5 is a dynamic brake for axonal growth.

During neuronal development, neurons undergo significant microtubule reorganization to shape axons and dendrites, establishing the framework for efficient wiring of the nervous system. Previous studies from our laboratory demonstrated the key role of kinesin-1 in driving microtubule-microtubule sliding, which provides the mechanical forces necessary for early axon outgrowth and regeneration in Drosophila melanogaster. In this study, we reveal the critical role of kinesin-5, a mitotic motor, in modulating the development of postmitotic neurons. Kinesin-5, a conserved homotetrameric motor, typically functions in mitosis by sliding antiparallel microtubules apart in the spindle. Here, we demonstrate that the Drosophila kinesin-5 homolog, Klp61F, is expressed in larval brain neurons, with high levels in ventral nerve cord (VNC) neurons. Knockdown of Klp61F using a pan-neuronal driver leads to severe locomotion defects and complete lethality in adult flies, mainly due to the absence of kinesin-5 in VNC motor neurons during early larval development. Klp61F depletion results in significant axon growth defects, both in cultured and in vivo neurons. By imaging individual microtubules, we observe a significant increase in microtubule motility, and excessive penetration of microtubules into the axon growth cone in Klp61F-depleted neurons. Adult lethality and axon growth defects are fully rescued by a chimeric human-Drosophila kinesin-5 motor, which accumulates at the axon tips, suggesting a conserved role of kinesin-5 in neuronal development. Altogether, our findings show that at the growth cone, kinesin-5 acts as a brake on kinesin-1-driven microtubule sliding, preventing premature microtubule entry into the growth cone. This regulatory role of kinesin-5 is essential for precise axon pathfinding during nervous system development.

Single-cell RNA sequencing reveals anti-tumor potency of CD56+ NK cells and CD8+ T cells in humanized mice via PD-1 and TIGIT co-targeting.

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma patient-derived xenografts (HCC-PDX) encounter limitations in NK cell infiltration, hindering studies on NK cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA sequencing (scRNA-seq) to identify potential anti-HCC treatments. A single administration of adeno-associated virus carrying human interleukin-15 reinstated persistent NK cell reconstitution and infiltration in HCC-PDX in humanized mice. scRNA-seq revealed NK cell and T cell subpopulations with heightened PDCD1 and TIGIT levels. Notably, combination therapy with anti-PD-1 and anti-TIGIT antibodies alleviated HCC burden in humanized mice, demonstrating NK cell-dependent efficacy. Bulk-RNA sequencing analysis also revealed significant alterations in the tumor transcriptome that may contribute to further resistance after combination therapy, warranting further investigations. As an emerging strategy, ongoing clinical trials with anti-PD-1 and anti-TIGIT antibodies provide limited data. The improved humanized mouse HCC-PDX model not only sheds light on the pivotal role of NK cells but also serves as a robust platform for evaluating safety and anti-tumor efficacy of combination therapies and other potential regimens, complementing clinical insights.

CPEB2-activated Prdm16 translation promotes brown adipocyte function and prevents obesity.

OBJECTIVE: Brown adipose tissue (BAT) plays an important role in mammalian thermogenesis through the expression of uncoupling protein 1 (UCP1). Our previous study identified cytoplasmic polyadenylation element binding protein 2 (CPEB2) as a key regulator that activates the translation of Ucp1 with a long 3'-untranslated region (Ucp1L) in response to adrenergic signaling. Mice lacking CPEB2 or Ucp1L exhibited reduced UCP1 expression and impaired thermogenesis; however, only CPEB2-null mice displayed obesogenic phenotypes. Hence, this study aims to investigate how CPEB2-controlled translation impacts body weight. METHODS: Body weight measurements were conducted on mice with global knockout (KO) of CPEB2, UCP1 or Ucp1L, as well as those with conditional knockout of CPEB2 in neurons or adipose tissues. RNA sequencing coupled with bioinformatics analysis was used to identify dysregulated gene expression in CPEB2-deficient BAT. The role of CPEB2 in regulating PRD1-BF1-RIZ1 homologous-domain containing 16 (PRDM16) expression was subsequently confirmed by RT-qPCR, Western blotting, polysomal profiling and luciferase reporter assays. Adeno-associated viruses (AAV) expressing CPEB2 or PRDM16 were delivered into BAT to assess their efficacy in mitigating weight gain in CPEB2-KO mice. RESULTS: We validated that defective BAT function contributed to the increased weight gain in CPEB2-KO mice. Transcriptomic profiling revealed upregulated expression of genes associated with muscle development in CPEB2-KO BAT. Given that both brown adipocytes and myocytes stem from myogenic factor 5-expressing precursors, with their cell-fate differentiation regulated by PRDM16, we identified that Prdm16 was translationally upregulated by CPEB2. Ectopic expression of PRDM16 in CPEB2-deprived BAT restored gene expression profiles and decreased weight gain in CPEB2-KO mice. CONCLUSIONS: In addition to Ucp1L, activation of Prdm16 translation by CPEB2 is critical for sustaining brown adipocyte function. These findings unveil a new layer of post-transcriptional regulation governed by CPEB2, fine-tuning thermogenic and metabolic activities of brown adipocytes to control body weight.

Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.

Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.

The impact of human capital misallocation on green economy efficiency: Empirical analysis of Chinese urban agglomerations.

This paper uses panel data of 260 prefecture-level cities from 2000 to 2019 to explore spatial characteristics such as spatiotemporal divergence and dynamic convergence based on measuring the level of human capital misallocation in Chinese cities and empirically tests the green development effect of human capital misallocation. The study finds that: ① the human capital misallocation levels of the country and the eight major urban agglomerations show a fluctuating downward trend. ② Divergences in human capital misallocation continue to narrow across the country and urban agglomerations, and the difference between inter-urban agglomerations is the primary source of regional difference. ③ The YRD, PRD, MYR, HC, and CP have significant σ-convergence characteristics of human capital misallocation. Meanwhile, the country and each urban agglomeration show significant spatial absolute ß-convergence and conditional ß-convergence trends. ④ Human capital misallocation significantly negatively affects green economic efficiency, inhibiting green economy efficiency. Therefore, in the future, it is necessary to improve the match between regional industrial structure and human capital allocation through a combination of targeted policy guidance and market mechanisms tailored to local conditions to enhance the efficiency of the green economy. The significance of the study lies in accelerating the accumulation of human capital while realizing the appropriate matching of human capital, releasing the human capital dividend to the maximum extent, and boosting the structural reform of the labor market to realize the transformation of the green economy.