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Abstract PCIF1 (phosphorylated CTD interacting factor 1) is the first reported RNA N6,2′-O-dimethyladenosine (m6Am) methyltransferase. However, the pathological significance of PCIF1 and m6Am modification remains unknown. Here we find that both PCIF1 expression and m6Am modification are significantly elevated in gastric cancer tissues. Increased PCIF1 is associated with gastric cancer progression, and predicts poor prognosis. Silence of PCIF1 inhibits the proliferation and invasion of gastric cancer cells, and suppresses tumor growth and metastasis in mouse model. m6Am-seq analysis reveals TM9SF1 (transmembrane 9 superfamily member 1) as a target of PCIF1. PCIF1 modifies TM9SF1 mRNA with m6Am leading to decreased TM9SF1 translation. TM9SF1 reverses the effects of PCIF1 on gastric cancer cell aggressiveness. Collectively, our work uncovers an oncogenic function of PCIF1, providing insights into the critical role of m6Am modification in cancer progression.

Abstract The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a severe threat to humanity. Rapid and comprehensive analysis of both pathogen and host sequencing data is critical to track infection and inform therapies. In this study, we performed unbiased metatranscriptomic analysis of clinical samples from COVID-19 patients using a recently developed RNA-seq library construction method (TRACE-seq), which utilizes tagmentation activity of Tn5 on RNA/DNA hybrids. This approach avoids the laborious and time-consuming steps in traditional RNA-seq procedure, and hence is fast, sensitive, and convenient. We demonstrated that TRACE-seq allowed integrated characterization of full genome information of SARS-CoV-2, putative pathogens causing coinfection, antibiotic resistance, and host response from single throat swabs. We believe that the integrated information will deepen our understanding of pathogenesis and improve diagnostic accuracy for infectious diseases.

Tn5-mediated transposition of double-strand DNA has been widely utilized in various high-throughput sequencing applications. Here, we report that the Tn5 transposase is also capable of direct tagmentation of RNA/DNA hybrids in vitro. As a proof-of-concept application, we utilized this activity to replace the traditional library construction procedure of RNA sequencing, which contains many laborious and time-consuming processes. Results of Transposase-assisted RNA/DNA hybrids Co-tagmEntation (termed ‘TRACE-seq’) are compared to traditional RNA-seq methods in terms of detected gene number, gene body coverage, gene expression measurement, library complexity, and differential expression analysis. At the meantime, TRACE-seq enables a cost-effective one-tube library construction protocol and hence is more rapid (within 6 hr) and convenient. We expect this tagmentation activity on RNA/DNA hybrids to have broad potentials on RNA biology and chromatin research.

Sarcopenia refers to an age-related systemic skeletal muscle disorder, which is characterized by loss of muscle mass and weakening of muscle strength. Gut microbiota can affect skeletal muscle through a variety of mechanisms. Gut microbiota present distinct features among elderly people and sarcopenia patients, including a decrease in microbial diversity, which might be associated with the quality and function of the skeletal muscle. There might be a gut-muscle axis; where gut microbiota and skeletal muscle may affect each other bi-directionally. Skeletal muscle can affect the biodiversity of the gut microbiota, and the latter can, in turn, affect the anabolism of skeletal muscle. This review examines recent studies exploring the relationship between gut microbiota and skeletal muscle, summarizes the effects of exercise on gut microbiota, and discusses the possible mechanisms of the gut-muscle axis.

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes, in which the Indian hedgehog (IHH) and parathyroid hormone-related protein-parathyroid hormone-1 receptor (PTHrP-PTH1R) feedback loop is crucial. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) branch of the unfolded protein response (UPR) is essential for normal cartilage development. However, the precise role of ER stress effector IRE1α, encoded by endoplasmic reticulum to nucleus signaling 1 (ERN1), in skeletal development remains unknown. Herein, we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone growth. ERN1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth plates. Its deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and differentiation. XBP1s, produced by p-IRE1α-mediated splicing, binds and up-regulates PTH1R and IHH, which coordinate cartilage development. Meanwhile, ER stress cannot be activated normally in ERN1-deficient chondrocytes. In conclusion, ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER stress. ERN1 may have a potential role as a new target for cartilage growth and maturation.

This study investigates the impact of dry heat pretreatment on the functionality of soy, chickpea, and pea protein ingredients for use in texturized vegetable protein (TVP) production via low moisture extrusion. The protein powders were heat-treated at temperatures ranging from 80 °C to 160 °C to modulate the extent of protein denaturation and assess their effects on RVA pasting behavior, water absorption capacity (WAC), and color attributes. The results indicate that the pretreatment temperature significantly influenced the proteins’ functional properties, with an optimal temperature of 120 °C enhancing pasting properties and maintaining WAC, while a higher pretreatment temperature of 160 °C led to diminished ingredient functionality. Different protein sources exhibited distinct responses to heat pretreatment. The subsequent extrusion processing revealed significant changes in extrudate density and color, with increased density and darkness observed at higher pretreatment temperatures. This research provides insights into the interplay between protein sources, pretreatment conditions, and extrusion outcomes, highlighting the importance of controlled protein denaturation for developing high-quality, plant-based meat analogues. The findings have broad implications for the optimization of meat analogue manufacturing, with the aim of enhancing the sensory experience and sustainability of plant-based foods.

IntroductionIndividuals with 17-beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency face a multitude of challenges, primarily concerning genital appearance, potential malignancy risks, and fertility issues. This study reports our findings from an investigation involving five individuals affected by 17β-HSD3 deficiency, ranging in age from pre-adolescence to adolescence. Notably, we identified four previously unreported mutations in these subjects.MethodsOur study included a comprehensive evaluation to determine the potential occurrence of testicular tumors. The methods involved clinical examinations, genetic testing, hormone profiling, and patient history assessments. We closely monitored the progress of the study subjects throughout their treatment.ResultsThe results of this evaluation conclusively ruled out the presence of testicular tumors among our study subjects. Moreover, four of these individuals successfully underwent gender transition. Furthermore, we observed significant improvements in genital appearance following testosterone treatment, particularly among patients in the younger age groups who received appropriate treatment interventions.DiscussionThese findings underscore the critical importance of early intervention in addressing concerns related to genital appearance, based on our extensive clinical experience and assessments. In summary, our study provides insights into the clinical aspects of 17β-HSD3 deficiency, emphasizing the vital significance of early intervention in addressing genital appearance concerns. This recommendation is supported by our comprehensive clinical assessments and experience.

ObjectiveThe review aimed to compare outcomes of pericapsular nerve group block (PENG) vs. fascia iliaca compartment block (FICB) for patients undergoing hip surgeries.MethodsRandomized controlled trials (RCTs) published in the databases of PubMed, CENTRAL, Embase, and Web of Science comparing PENG vs. FICB for pain control after hip surgeries were included in the review.ResultsSix RCTs were included. 133 patients received PENG block and were compared with 125 patients receiving FICB. Our analysis showed no difference in 6 h (MD: −0.19 95% CI: −1.18, 0.79 I2 = 97% p = 0.70), 12 h (MD: 0.04 95% CI: −0.44, 0.52 I2 = 72% p = 0.88) and 24 h (MD: 0.09 95% CI: −1.03, 1.21 I2 = 97% p = 0.87) pain scores between PENG and FICB groups. Pooled analysis showed that mean opioid consumption in morphine equivalents was significantly less with PENG as compared to FICB (MD: −8.63 95% CI: −14.45, −2.82 I2 = 84% p = 0.004). Meta-analysis of three RCTs showed no variation in the risk of postoperative nausea and vomiting in the two groups. The quality of evidence on GRADE was mostly moderate.ConclusionModerate quality of evidence suggests that PENG may result in better analgesia than FICB in patients undergoing hip surgeries. Data on motor-sparing ability and complications are scarce to draw conclusions. Further large-scale and high-quality RCTs should be conducted to supplement current findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022350342.

Abstract Background Autophagy and ER stress are involved in maintaining some well-orchestrated mechanisms aimed at either restoring cellular homeostasis or performing cell death. Autophagy is a well-defined process which governs overall cellular stress outcomes. Selective degradation of the ER mediated by autophagy occurs through a specific type of autophagy called ER-phagy, which ensures ER protein homeostasis. Methods Immunoblotting and RT-PCR were used to evaluate the expression of ATG5 and ATG7 in chondrocyte. Western blotting, Flow cytometry,immunofluorescence cell staining and confocal microscope were used to examine the effect of ATG5 and ATG7 on autophagy, ER stress, cell apoptosis and cell proliferation. Transmission electron microscope and confocal microscope were performed to visualize the autophagy flux and autolysosome formation. The role of ATG5 and ATG7 overexpression on the PERK pathway inhibitor were detected by immunoblotting and treatment with inhibitors. Results In current study, we demonstrated that Tm-induced ER stress can activate autophagy while Rapamycin-induced autophagy can inhibit ER stress in chondrocyte. Autophagy related protein ATG5 or ATG7 can promote autophagy and inhibit ER stress individually, and their combined effect can further improve the autophagy enhancement and the ER stress repression. Moreover, ATG5, ATG7 and ATG5 + ATG7 lead cells into more S phase, increase the number of S phase and inhibit apoptosis as well. ATG5, ATG7 and ATG5 + ATG7 regulate autophagy, ER stress, apoptosis and cell cycle through PERK signaling, a vital UPR branch pathway. Conclusions ATG5 and ATG7 connect autophagy with ER stress through PERK signaling. The protective effect of ATG5/7 overexpression on chondrocyte survival relys on PERK signaling. The effect of siPERK and siNrf2 on the cytoprotective effect of ATG5/7 are of synergism, while the effect of siPERK and siATF4 are of antagonism. PERK signal may be the pivot for autophagy, ER homeostasis and ER-phagy in chondrocyte.

In this study, schorl was used as an effective adsorbent for ciprofloxacin removal from wastewater. The adsorption performance, mechanism and effect of metal ion on sorption were investigated. Adsorption capacity reached a maximum (8.49 mg/g) when the pH value was 5.5. The pseudo-second-order kinetic model and Freundlich model could better describe the experimental data. The negative ΔH (–22.96 KJ/mol) value showed that the adsorption process was exothermic. The results also indicated physical adsorption existed on the adsorption process, which was in agreement with the analysis of X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy. The desorption rate could reach 94%, which suggested that schorl had a good desorption and regeneration performance. Coexisting ions, such as Cu2+ and Al3+, could obviously inhibit adsorption, and the inhibition from Al3+ was significantly higher than that from Cu2+. However, the additional Zn2+ could slightly promote the adsorption.

Perishable fresh vegetables that do not meet cosmetic standards and by-products of processing are currently wasted. Broccoli and carrots were selected as model vegetables to demonstrate that they can be converted into nutrient-dense and shelf-stable food ingredients and formulated into convenient ready-to-eat snacks. Broccoli powder was a rich source of protein (30%) and dietary fibre (28%). Carrot powder had lower protein (6.5%) and dietary fibre content (24%) and was higher in sugar (47%) compared to broccoli powder (21%). Compared to the whole-vegetable powders, pomace powders were richer in fibre but had lower levels of total carbohydrates. There was a reduced expansion of extruded snacks with increasing levels of the vegetable component in the formulation. Processing and storage for 12 months at 25 °C or 40 °C resulted in changes in the measured soluble phenolic content. Changes during storage were dependent on the temperature and time. The changes may be in part due to the changes in the material properties of the matrix as a consequence of processing and storage, which affect extractability. The conversion of perishable vegetables and pomace into shelf-stable nutrient-dense food ingredients and products will reduce food loss and waste in the vegetable industry.

Spray dried microencapsulated formulations [25% protein:25% sugar:25% resistant starch (RS):20% oil:5% Lactobacillus rhamnosus GG (LGG)] were compared with commercial freeze dried LGG during non-refrigerated storage with or without packaging. Microencapsulated spray dried LGG was more stable on storage at 25 °C (32, 57 or 70% relative humidity) than freeze dried LGG. The viability of microencapsulated formulations was greater in formulations containing dried glucose syrup compared with glucose, but the type of protein (whey protein isolate or hydrolysed whey protein) has less of an effect. Viability was correlated to the properties of water in the formulations. After long term storage (12 months, 25 °C) in moisture barrier bags, viability was >107 CFU/g for FD LGG and microencapsulated formulations without glucose. Only the microencapsulated formulations were free-flowing and maintained an acceptable colour. There are benefits of microencapsulation for long term packaged non-refrigerated storage and short term storage in open environments.

This study compared the survival of spray dried microencapsulated Lactobacillus rhamnosus GG (LGG) added into apple juice or citrate buffer (pH 3.5) and stored at 4 or 25 °C over a 5-week period. The LGG was encapsulated in matrices comprising (i) whey protein isolate (WPI) alone, (ii) WPI in combination with a physically-modified resistant starch (RS) at various ratios (4:1, 1:1 and 1:4), or (iii) RS alone. All microencapsulated LGG formulations containing WPI alone or WPI in combination with RS provided better protection to LGG in apple juice or citrate buffer compared to the formulation containing RS alone. We suggest that the protection afforded by formulations containing WPI alone or in combination with RS is due to the ability of WPI to create a buffered microenvironment within the hydrated colloid particle surrounding the embedded LGG, thus isolating the bacteria from the stresses of the low pH external environment.