Endurance exercise-induced histone methylation modification involved in skeletal muscle fiber type transition and mitochondrial biogenesis.

Skeletal muscle is a highly heterogeneous tissue, and its contractile proteins are composed of different isoforms, forming various types of muscle fiber, each of which has its own metabolic characteristics. It has been demonstrated that endurance exercise induces the transition of muscle fibers from fast-twitch to slow-twitch muscle fiber type. Herein, we discover a novel epigenetic mechanism for muscle contractile property tightly coupled to its metabolic capacity during muscle fiber type transition with exercise training. Our results show that an 8-week endurance exercise induces histone methylation remodeling of PGC-1α and myosin heavy chain (MHC) isoforms in the rat gastrocnemius muscle, accompanied by increased mitochondrial biogenesis and an elevated ratio of slow-twitch to fast-twitch fibers. Furthermore, to verify the roles of reactive oxygen species (ROS) and AMPK in exercise-regulated epigenetic modifications and muscle fiber type transitions, mouse C2C12 myotubes were used. It was shown that rotenone activates ROS/AMPK pathway and histone methylation enzymes, which then promote mitochondrial biogenesis and MHC slow isoform expression. Mitoquinone (MitoQ) partially blocking rotenone-treated model confirms the role of ROS in coupling mitochondrial biogenesis with muscle fiber type. In conclusion, endurance exercise couples mitochondrial biogenesis with MHC slow isoform by remodeling histone methylation, which in turn promotes the transition of fast-twitch to slow-twitch muscle fibers. The ROS/AMPK pathway may be involved in the regulation of histone methylation enzymes by endurance exercise.

Isovaleramide attenuates ethylene glycol poisoning-induced acute kidney injury and reduces mortality by inhibiting alcohol dehydrogenase activity in rats.

We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning-induced acute kidney injury. Sprague-Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high-performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM-1, neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (L-FABP) by ELISA. Additionally, Western blotting results showed that ISO down-regulated the expression of apoptotic factors Bax and cleaved caspase-3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl-2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning-induced acute kidney injury.

Correlation between symptom experience and fear of cancer recurrence in postoperative breast cancer patients undergoing chemotherapy in China: A cross-sectional study.

OBJECTIVE: To analyze the relationship between experience of symptoms (e.g., pain, fatigue) and fear of cancer recurrence (FCR) in Chinese postoperative patients with breast cancer undergoing chemotherapy. METHODS: A total of 225 patients were recruited using convenience sampling. The Fear of Cancer Recurrence Inventory-Chinese Version and the Symptom Experience Index were used to collect data. The Mann-Whitney U test, Spearman's correlation, and multivariate analysis were employed to explore the relationships between symptom experience and FCR. RESULTS: The total Fear of Cancer Recurrence Inventory score in postoperative patients with breast cancer undergoing chemotherapy was 43.19±22.83, and >64.0% of participants exhibited significant fear of cancer recurrence. The total score of symptom experience was 27.41±16.77, including scores of symptom severity (16.91±8.70) and symptom distress (10.50±8.89). Participants' symptom experience was positively correlated with fear of cancer recurrence (r = 0.353, P < 0.001). Patients with clinically relevant FCR had higher scores for total symptom experience (Z = -3.911, P<0.001), symptom severity (Z = -3.245, P = 0.001), and symptom distress (Z = -4.185, P<0.001), compared to patients without clinically relevant FCR. Symptom experience (b = 0.511, t = 6.474, P<0.001), age (b = -0.591, t = -4.201, P<0.001), and educational level (b = 4.147, t = 3.955, P<0.001) were statistically correlated with FCR, accounting for 27.0% of the variance. Among these variables, symptom experience demonstrated the strongest correlation, with a beta value of 0.371. CONCLUSION: This study followed others in identifying a cross-sectional relationship between symptom experience and FCR. Further prospective research is required to better understand the nature of this relationship.

α-linolenic acid mitigates microglia-mediated neuroinflammation of schizophrenia in mice by suppressing the NF-κB/NLRP3 pathway via binding GPR120-ß-arrestin 2.

BACKGROUND: Schizophrenia (SCZ) is a heterogeneous psychiatric disorder that is poorly treated by current therapies. Emerging evidence indicates that SCZ is closely correlated with a persistent neuroinflammation. α-linolenic acid (ALA) is highly concentrated in the brain and represents a modulator of the immune system by decreasing the inflammatory response in chronic metabolic diseases. This study was first designed to investigate the potential role of dietary ALA on cognitive function and neuroinflammation in mice with SCZ. METHODS: In vivo, after 2 weeks of modeling, mice were treated with dietary ALA treatment for 6 weeks. In vitro, inflammation model was created using lipopolysaccharide as an inducer in BV2 microglial cells. RESULTS: Our results demonstrated that ALA alleviated cognitive impairment and enhanced synaptic plasticity in mice with SCZ. Moreover, ALA mitigated systematic and cerebral inflammation through elevating IL-10 and inhibiting IL-1ß, IL-6, IL-18 and TNF-α. Furthermore, ALA notably inhibited microglia and pro-inflammatory monocytes, as well as microglial activation andpolarization. Mechanistically, ALA up-regulated the expressions of G protein coupled receptor (GPR) 120 and associated ß-inhibitor protein 2 (ß-arrestin2), accompanied by observable weakened levels of transforming growth factor-ß activated kinase 1 (TAK1), NF-κB p65, cysteine proteinase-1 (caspase-1), pro-caspase-1, associated speck-like protein (ASC) and NLRP3. In vitro, ALA directly restrained the inflammation of microglia by decreasing the levels of pro-inflammatory factors and regulating microglial polarization via GPR120-NF-κB/NLRP3inflammasome signaling pathway, whereas AH7614 definitely eliminated this anti-inflammatory effect of ALA. CONCLUSION: Dietary ALA ameliorates microglia-mediated neuroinflammation by suppressing the NF-κB/NLRP3 pathway via binding GPR120-ß-arrestin2.

Early peripheral perfusion index predicts 28-day outcome in patients with septic shock.

BACKGROUND: To investigate the prognostic value of the peripheral perfusion index (PPI) in patients with septic shock. METHODS: This prospective cohort study, conducted at the emergency intensive care unit of Peking University People's Hospital, recruited 200 patients with septic shock between January 2023 and August 2023. These patients were divided into survival (n=84) and death (n=116) groups based on 28-day outcomes. Clinical evaluations included laboratory tests and clinical scores, with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission. Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses. Receiver operator characteristic (ROC) curve was used to assess predictive performance. Mortality rates were compared, and Kaplan-Meier survival plots were created. RESULTS: Compared to the survival group, patients in the death group were older and had more severe liver damage and coagulation dysfunction, necessitating higher norepinephrine doses and increased fluid replacement. Higher lactate levels and lower PPI levels at 0 h, 6 h, and 12 h were observed in the death group. Multivariate Cox regression identified prolonged prothrombin time (PT), decreased 6-h PPI and 12-h PPI as independent risk factors for death. The area under the curves for 6-h PPI and 12-h PPI were 0.802 (95% CI 0.742-0.863, P<0.001) and 0.945 (95% CI 0.915-0.974, P<0.001), respectively, which were superior to Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) scores (0.864 and 0.928). Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups (6-h PPI: 77.52% vs. 22.54%; 12-h PPI: 92.04% vs. 13.79%, P<0.001). CONCLUSION: PPI may have value in predicting 28-day mortality in patients with septic shock.

The impact of internet usage preferences on labor income: Evidence from China.

BACKGROUND: The widespread application and iterative updating of computers and Internet communication technologies have not only increased productivity and enhanced intra- and inter-enterprise collaboration, but have also led to significant changes in the labor market and residents' labor income. In the digital era, accepting digital technology and possessing a certain degree of digital literacy have become the necessary abilities for people to survive and develop. However, the differences in digital literacy caused by individual differences will inevitably bring about a series of chain reactions. Therefore, it is necessary to study the subtle impact of Internet usage preference on residents' labor income in the context of digital transformation to promote digital equity. OBJECTIVE: This study aims to empirically analyze micro-level survey data to reveal the impact of individual differences in internet usage preferences on their labor income. The findings provide theoretical references for government policy formulation and individual development. METHODS: A function model was established to analyze the impact of individual internet usage preferences on labor income. Relevant data from the authoritative Chinese General Social Survey (CGSS2017) were selected, and empirical analyses for significance, heterogeneity, and robustness were conducted using the ZINB and CMP models in the Stata statistical software. CONCLUSION: (1) Higher Internet Usage Frequency (IUF) increases the likelihood of higher income. (2) Engaging in Online Social Networking (OSN) helps in accumulating social capital, leading to higher labor income. Meanwhile, participating in Online Entertainment (OE) relieves work and life stresses, thereby increasing labor income. Proficiency in Accessing Online Information (AOI) is associated with higher labor income, while frequent involvement in Online Business (OB) is correlated with higher personal income. Additionally, the Marginal utility of these internet usage preferences indicate that OB > AOI > OSN > OE. (3) Individual variations in physical, psychological, and social characteristics significantly influence the labor income effects of internet usage preferences. (4) There are substantial differences in the labor income effects of internet usage preferences between urban and rural areas and across different regions. (5) Education attainment has a positive mediating effect on the labour income effect of individual Internet use preferences, and enhancing residents' digital literacy has a positive effect on increasing their labour income and alleviating inequality in digital gains. (6) The popularity of Internet technology is the background that triggers an individual's Internet use, and the acceptance of a particular Internet technology is catalyzed by an individual's perception of the value and difficulty of mastering that technology; an individual's biased learning or proficiency in a particular Internet technology in order to gain higher competitiveness and value in the labour market is an important internal driving force.

Exploring the genuine psychological experiences of novice nurses at emergency resuscitation events: A qualitative interview study.

Purpose: An emergency rescue situation is an inevitable challenge in medical work, requiring collaborative efforts from healthcare professionals. Due to a lack of practical experience, novice nurses may encounter difficulties in successfully managing emergency resuscitation events. This study aimed to analyse the authentic psychological experiences of novice nurses participating in emergency resuscitation events by exploring applicable coping methods and management strategies. Methods: This study utilized a hermeneutic phenomenological qualitative research method. We employed purposive sampling to select 27 Novice nurses from West China Hospital of Sichuan University for face-to-face semistructured interviews. Data collection for this study was conducted from November 2023 to January 2024. The interviews were fully audio-recorded and transcribed verbatim. The data were coded, categorized and summarized with the help of Nvivo 20.0 software based on the interpretation of phenomenological research methods. Thematic analysis was performed to deeply analyse and extract corresponding themes. The COREQ criteria were used to guide the reporting of this study. Results: The authentic psychological experiences of novice nurses participating in emergency rescue events mainly include six aspects: lack of rescue knowledge reserves and related abilities, psychological and emotional changes, psychological stress after the rescue, rational arrangement of manpower, team cooperation, and postevent reflection and learning. Their authentic psychological experiences directly affect whether novice nurses can effectively respond to emergency rescue events. Conclusions: This study suggested enhancing novice nurses' knowledge, improving their resuscitation skills, and improving their psychological well-being during resuscitation events. It advocates for organized staffing, effective teamwork, and robust support systems to empower novice nurses and improve their overall capabilities in emergencies. These findings offer valuable insights for future research in this area.

Feasibility of 3D MRI fingerprinting for rapid knee cartilage T1, T2, and T1ρ mapping at 0.55T: Comparison with 3T.

Low-field strength scanners present an opportunity for more inclusive imaging exams and bring several challenges including lower signal-to-noise ratio (SNR) and longer scan times. Magnetic resonance fingerprinting (MRF) is a rapid quantitative multiparametric method that can enable multiple quantitative maps simultaneously. To demonstrate the feasibility of an MRF sequence for knee cartilage evaluation in a 0.55T system we performed repeatability and accuracy experiments with agar-gel phantoms. Additionally, five healthy volunteers (age 32 ± 4 years old, 2 females) were scanned at 3T and 0.55T. The MRI acquisition protocols include a stack-of-stars T1ρ-enabled MRF sequence, a VIBE sequence with variable flip angles (VFA) for T1 mapping, and fat-suppressed turbo flash (TFL) sequences for T2 and T1ρ mappings. Double-Echo steady-state (DESS) sequence was also used for cartilage segmentation. Acquisitions were performed at two different field strengths, 0.55T and 3T, with the same sequences but protocols were slightly different to accommodate differences in signal-to-noise ratio and relaxation times. Cartilage segmentation was done using five compartments. T1, T2, and T1ρ values were measured in the knee cartilage using both MRF and conventional relaxometry sequences. The MRF sequence demonstrated excellent repeatability in a test-retest experiment with model agar-gel phantoms, as demonstrated with correlation and Bland-Altman plots. Underestimation of T1 values was observed on both field strengths, with the average global difference between reference values and the MRF being 151 ms at 0.55T and 337 ms at 3T. At 0.55T, MRF measurements presented significant biases but strong correlations with the reference measurements. Although a larger error was present in T1 measurements, MRF measurements trended similarly to the conventional measurements for human subjects and model agar-gel phantoms.

Effects of an LPSO Phase Induced by Zn Addition on the High-Temperature Properties of Mg-9Gd-2Nd-(1.5Zn)-0.5Zr Alloy.

In this study, we prepared Mg-9Gd-2Nd-0.5Zr, referred to as alloy I, and Mg-9Gd-2Nd-1.5Zn-0.5Zr, referred to as alloy II. The effects of a long-period stacking ordered (LPSO) phase induced by Zn addition on the high-temperature mechanical properties and fracture morphology of alloy I and alloy II at different temperatures (25 °C, 200 °C, 225 °C, and 250 °C) were studied using optical microscopy (OM), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM). The results indicate that Mg5RE at the crystal boundary of the as-cast alloy I transformed into (MgZn)3RE (as-cast alloy II) by the addition of Zn. After solid solution treatment, the secondary phase in alloy I completely disappeared, and there were still residual secondary phases in block-like and needle-like structures in alloy II, while layered LPSO phases precipitated in the matrix. During the high-temperature tensile test, the yield and tensile strength of alloy I decreased significantly with the increase in temperature, while the elongation increased. Compared to alloy I, the yield strength of alloy II with an LPSO phase showed an increasing trend at 25 °C~200 °C and then decreased when the temperature reached around 250 °C. The thermal stability was significantly enhanced, and the elongation was also higher than that of alloy I. As the temperature increased, the fracture surface of alloy I showed increased folding, bending of scratches, and crack enlargement. However, the fracture surface of alloy II remained largely unchanged, with only minor wrinkles and cracks appearing at temperatures reaching 250 °C.

Enhancement of Bone Repair in Diabetic Rats with Metformin-Modified Silicified Collagen Scaffolds.

Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.

A bioactive composite sponge based on biomimetic collagen fibril and oxidized alginate for noncompressible hemorrhage and wound healing.

The study focuses on developing a bioactive shape memory sponge to address the urgent demand for short-term rapid hemostasis and long-term wound healing in noncompressible hemorrhage cases. A composite sponge was created by spontaneously generating pores and double cross-linking under mild conditions using biomimetic collagen fibril (BCF) and oxidized alginate (OA) as natural backbone, combined with an inert calcium source (Ca) from CaCO3-GDL slow gelation mechanism. The optimized BCF/OACa (5/5) sponge efficiently absorbed blood after compression and recovered to its original state within 11.2 ± 1.3 s, achieving physical hemostatic mechanism. The composite sponge accelerated physiological coagulation by promoting platelet adhesion and activation through BCF, as well as enhancing endogenous and exogenous hemostatic pathways by Ca2+. Compared to commercial PVA expanding hemostatic sponge, the composite sponge reduced bleeding volume and shortened hemostasis time in rat liver injury pick and perforation wound models. Additionally, it stimulated fibroblast migration and differentiation, thus promoting wound healing. It is biodegradable with low inflammatory response and promotes granulation tissue regeneration. In conclusion, this biocomposite sponge provides multiple hemostatic pathways and biochemical support for wound healing, is biologically safe and easy to fabricate, process and use, with significant potential for clinical translation and application.

A high-strength collagen-based antimicrobial film grafted with ε-polylysine fabrication by riboflavin-mediated ultraviolet irradiation for pork preservation.

In this study, a UV-cured collagen-based film (C-P-H film) with high mechanical strength and antimicrobial properties was developed by riboflavin-mediated ultraviolet irradiation of collagen solution containing histidine-modified ε-polylysine. Fourier transform infrared analysis indicated that covalent cross-linking was formed between the collagen molecule and the histidine-grafted ε-polylysine. Compared with the pure collagen film, the C-P-H film containing 5 wt% histidine-modified ε-polylysine showed higher tensile strength (145.98 MPa), higher thermal denaturation temperature (76.5 °C), lower water vapor permeability (5.54 × 10-11 g m-1 s-1 Pa) and excellent antimicrobial activities against Escherichia coli and Staphylococcus aureus. In addition, the wrapping of the C-P-H film effectively inhibited bacterial growth of pork during storage time, successfully prolonging the shelf-life of pork by approximately 4 days compared to that of plastic wrap. These results suggested that collagen-based film grafted with histidine-modified ε-polylysine via riboflavin-mediated ultraviolet irradiation process had a great potential for pork preservation.

The value of nanopore sequencing as a diagnostic tool in tuberculous meningitis: A protocol of systematic review and meta-analysis.

BACKGROUND: Rapid diagnosis of tuberculous meningitis (TBM) remains very difficult. Nanopore sequencing is gaining ground in the field of rapid tuberculosis (TB) diagnostics. The purpose of this study was to complete a protocol to guide the conduct of a systematic review and meta-analysis evaluating the accuracy of nanopore sequencing for the rapid diagnosis of TBM. METHODS: In accordance with the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines, we completed this protocol, which was also registered on the PROSPERO platform. We will search the EMBASE, PubMed, the Cochrane Library, Wanfang database, and China National Knowledge Infrastructure databases for literature that evaluated the accuracy of nanopore sequencing for rapid diagnosis of TBM and screen them according to the inclusion and exclusion criteria, and qualified literature will be extracted with relevant data for further analysis. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used for evaluating the methodological quality of included studies. Stata (V 15.0; Stata Corp., College Station, TX, the USA) with midas module will be used to perform relevant meta-analysis. Heterogeneity between studies will be assessed by I2 statistics. When significant heterogeneity exists between studies, we will conduct meta-regression analyses, subgroup analyses and sensitivity analyses to further explore the sources of heterogeneity. CONCLUSION: We completed this study protocol, and this systematic review and meta-analysis will be the first systematic evaluation of the role of nanopore sequencing in the rapid diagnosis of TBM, which will allow clinicians to have a better understanding of the test. TRIAL REGISTRATION: Systematic review registration PROSPERO Registration number: CRD42024549837.

AQP4- and Kir4.1-Mediated Müller Cell Oedema Is Involved in Retinal Injury Induced By Hypobaric Hypoxia.

Hypobaric hypoxia is the main cause of high-altitude retinopathy (HAR). Retinal oedema is the key pathological change in HAR. However, its pathological mechanism is not clear. In this study, a 5000-m hypobaric hypoxic environment was simulated. Haematoxylin and eosin (H&E) staining and electrophysiological (ERG) detection were used to observe the morphological and functional changes in the retina of mice under hypobaric hypoxia for 2-72 h. Toluidine blue staining and transmission electron microscopy were used to observe the morphology of Müller cells in the hypobaric hypoxia groups. The functional changes and oedema mechanism of Müller cells were detected by immunofluorescence and western blotting. The expression levels of glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and inwardly rectifying potassium channel subtype 4.1 (Kir4.1) in Müller cells were quantitatively analysed. This study revealed that retinal oedema gradually increased with prolonged exposure to a 5000-m hypobaric hypoxic environment. In addition, the ERG showed that the time delay and amplitude of the a-wave and b-wave decreased. The expression of GS decreased, and the expression of GFAP increased in Müller cells after exposure to hypobaric hypoxia for 4 h. At the same time, retinal AQP4 expression increased, and Kir4.1 expression decreased. The oedema and functional changes in Müller cells are consistent with the time point of retinal oedema. In conclusion, Müller cell oedema is involved in retinal oedema induced by hypobaric hypoxia. An increase in AQP4 and a decrease in Kir4.1 are the main causes of Müller cell oedema caused by hypobaric hypoxia.

LAIR1 promotes hepatocellular carcinoma cell metastasis and induces M2-macrophage infiltration through activating AKT-IKKß-p65 axis.

LAIR1, a receptor found on immune cells, is capable of binding to collagen and is involved in immune-related diseases. However, the precise contribution of LAIR1 expressed on hepatocellular carcinoma (HCC) cells to tumor microenvironment is still unclear. In our study, bioinformatics analysis and immunofluorescence were employed to study the correlation between LAIR1 levels and clinical indicators. Transwell and scratch tests were used to evaluate how LAIR1 affected the migration and invasion of HCC cells. The chemotactic capacity and alternative activation of macrophages were investigated using RT-qPCR, transwell, and immunofluorescence. To investigate the molecular mechanisms, transcriptome sequencing analysis, Western blot, nucleus/cytoplasm fractionation, ELISA, and cytokine microarray were employed. We revealed a significant correlation between the presence of LAIR1 and an unfavorable outcome in HCC. We indicated that LAIR1 promoted migration and invasion of HCC cells through the AKT-IKKß-p65 axis. Additionally, the alternative activation and infiltration of tumor-associated macrophages induced by LAIR1 were reliant on the upregulation of IL6 and CCL5 within this axis, respectively. In conclusion, blocking LAIR1 was found to be an effective approach in combating the cancerous advancement of HCC.

The BNB-GLID module regulates germline fate determination in Marchantia polymorpha.

Germline fate determination is a critical event in sexual reproduction. Unlike animals, plants specify the germline by reprogramming somatic cells at the late stages of their development. However, the genetic basis of germline fate determination and how it evolved during the land plant evolution are still poorly understood. Here, we report that the plant homeodomain finger protein GERMLINE IDENTITY DETERMINANT (GLID) is a key regulator of the germline specification in liverwort, Marchantia polymorpha. Loss of the MpGLID function causes failure of germline initiation, leading to the absence of sperm and egg cells. Remarkably, the overexpression of MpGLID in M. polymorpha induces the ectopic formation of cells with male germline cell features exclusively in male thalli. We further show that MpBONOBO (BNB), with an evolutionarily conserved function, can induce the formation of male germ cell-like cells through the activation of MpGLID by directly binding to its promoter. The Arabidopsis (Arabidopsis thaliana) MpGLID ortholog, MALE STERILITY1 (AtMS1), fails to replace the germline specification function of MpGLID in M. polymorpha, demonstrating that a derived function of MpGLID orthologs has been restricted to tapetum development in flowering plants. Collectively, our findings suggest the presence of the BNB-GLID module in complex ancestral land plants that has been retained in bryophytes, but rewired in flowering plants for male germline fate determination.

CYP17A1 Pathogenic Variants in 26 Chinese Patients with 17α-Hydroxylase Deficiency by Targeted Long-read Sequencing.

BACKGROUND: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a rare subtype of congenital adrenal hyperplasia (CAH) caused by homozygous or compound heterozygous pathogenic variants in the CYP17A1 gene. PURPOSE: This study aimed to identify and characterize pathogenic variants in individuals with 17-OHD, and to classify and validate the pathogenicity of novel variants. METHODS: Variants were identified via targeted long-read sequencing (TLRS) of the entire CYP17A1 gene in enrolled 17-OHD patients. The American College of Medical Genetics and Genomics guidelines were employed to assess the pathogenicity of novel variants. A minigene splicing assay was utilized to determine the impact of variants on RNA splicing. RESULTS: This study encompassed 26 patients with 17-OHD, detecting two trans pathogenic variants per patient using the TLRS method. A total of 20 pathogenic variants in the CYP17A1 were identified, with variant c.985_987delinsAA being the most frequent (28/52 alleles), followed by variant c.1459_1467del (4/52 alleles). Five novel variants including c.280T>C, c.470T>A, c.636_637del, c.866A>G, and c.1095del, were classified as pathogenic/likely pathogenic ones according to ACMG criteria. The minigene assay revealed c.866A>G in exon 5 causes a frameshift due to a 104 base pair deletion, while c.470T>A generates two transcripts, with vast majority spliced like the wild-type, and a small fraction lack 35 base pairs in the 5' flank of exon 3. CONCLUSION: The TLRS can determine the cis/trans orientation of two distant variants. Five novel pathogenic variants were reported, broadening the spectrum of CYP17A1 pathogenic variant. The variant c.866A>G, located deep in exon, affects gene function through mechanisms of aberrant splicing.

Hypoxia-responsive lncRNA MIR155HG promotes PD-L1 expression in hepatocellular carcinoma cells by enhancing HIF-1α mRNA stability.

The microenvironment of hepatocellular carcinoma (HCC) is characterized by hypoxia, which leads to immune evasion of HCC. Therefore, gaining a comprehensive understanding of the mechanism underlying the impact of hypoxia on HCC cells may provide valuable insights into immune checkpoint therapy. Based on analysis of databases and clinical samples, we observed that expression level of programmed cell death ligand 1 (PD-L1) and long non-coding RNA (lncRNA) MIR155HG in patients in the hypoxia group were higher than those in the non-hypoxia group. Furthermore, there was a positive correlation between the expression of PD-L1 and MIR155HG with that of HIF-1α. In vitro experiments using hypoxic treatment demonstrated an increase in PD-L1 and MIR155HG expression levels in HCC cells. While the hypoxia-induced upregulation of PD-L1 could be reversed by knocking down MIR155HG. Mechanistically, as a transcription factor, HIF-1α binds to the promoter region of MIR155HG to enhance its transcriptional activity under hypoxic conditions. Hypoxia acts as a stressor promoting nuclear output of ILF3 leading to increased binding of ILF3 to MIR155HG, thereby enhancing stability for HIF-1α mRNA. In vivo, knocking down MIR155HG inhibit subcutaneous tumor growth, reduce the expression of HIF-1α and PD-L1 within tumors; additionally, it enhances anti-tumor immunity response. These findings suggested that through inducing MIR155HG to interact with ILF3, hypoxia increases HIF-1α mRNA stability resulting in elevated PD-L1 expression in HCC and thus promoting immune escape. In summary, this study provides new insights into the effects of hypoxia on HCC immunosuppression.

The association of cognitive function and its changes with all-cause mortality among community-dwelling older adults.

Background: The association of cognitive function, its changes, and all-cause mortality has not reached a consensus, and the independence of the association between changes in cognitive function and mortality remains unclear. The purpose of this study was to evaluate the longitudinal association between baseline cognitive function and cognitive changes over 1 year with subsequent all-cause mortality among the older adults aged 60 and above. Methods: A prospective cohort study utilizing the Community Older Adults Health Survey data. Initiated in 2018, the study annually assessed all individuals aged 60+ in Dalang Town, Dongguan City. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). A total of 6,042 older adults individuals were included, and multivariate Cox proportional hazard models were used to examine cognitive function's impact on mortality. Results: Participants' median age was 70 years, with 39% men. Over a median 3.08-year follow-up, 525 died. Mortality risk increased by 6% per MMSE score decrease (adjusted HR = 1.06, 95%CI: 1.05-1.08). Compared to those with normal cognitive function at baseline, participants with mild cognitive impairment and moderate to severe cognitive impairment had significantly higher mortality risks (adjusted HR = 1.40, 95%CI: 1.07-1.82; HR = 2.49, 95%CI: 1.91-3.24, respectively). The risk of death was 5% higher for each one-point per year decrease in cognitive function change rate (HR = 1.05, 95%CI: 1.02-1.08). Compared with participants with stable cognitive function, those with rapid cognitive decline had a 79% increased risk of death (adjusted HR = 1.79, 95% CI: 1.11-2.87), with baseline cognitive function influencing this relationship significantly (P for interaction = 0.002). Conclusion: Baseline cognitive impairment and rapid cognitive decline are associated with higher all-cause mortality risks in Chinese older adults. Baseline function influences the mortality impact of cognitive changes.

Effects of psychological nursing in Parkinson's related depression patients undergoing functional magnetic resonance imaging: A randomized controlled trial.

BACKGROUND: Patients with Parkinson's disease (PD) often experience depression, and some may require magnetic resonance imaging (MRI) for diagnosis, which can lead to MRI failure due to claustrophobia. AIM: To explore the value of psychological interventions in successfully completing functional MRI scans of the brain for PD-related depression. METHODS: Ninety-six patients with PD were randomly divided into two groups. The control group (47 patients) received general care, and the experimental group (49 patients) received general care combined with psychological care. The Unified Parkinson's Disease Assessment Scale (UPDRS), Hamilton Depression Scale (HAMD), and Geriatric Depression Scale (GDS)-15 scores, heart rate, systolic blood pressure, and MRI-Anxiety Questionnaire (MRI-AQ) scores before and after the scan were recorded. The completion rate of magnetic resonance (MR) scanning, scanning duration, and image quality scores were recorded. RESULTS: Before scanning, no statistically significant difference was observed between the two groups in terms of heart rate, systolic blood pressure, and UPDRS, HAMD, GDS-15, and MRI-AQ scores. After scanning, systolic blood pressure, MRI-AQ score, and scan time in the experimental group were significantly lower than those in the control group, whereas the scan completion rate and image quality score were significantly higher than those in the control group. CONCLUSION: Psychological nursing interventions are helpful in alleviating PD-related depression and assessing MR depression scores and may be helpful in the successful completion of functional MRI scans of the patient's brain.