Four-in-one multifunctional self-driven photoelectrocatalytic system for water purification: Organics degradation, U(VI) reduction, electricity generation and disinfection against bacteria.

This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO2-decorated carbon felt (CF@TiO2) cathode is synthesized to enhance interfacial charge transfer, with TiO2 coating improving surface binding sites (edge TiO and adsorbed -OH) for UO22+ adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100 % of uranium within 0.5 h and simultaneously degrading 99.9 % of sulfamethoxazole (SMX) within 1.5 h, all while generating a maximum power output density (Pmax) of approximately 1065 µW·cm-2. The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4 % of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100 % of Escherichia coli within 0.5 h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation.

Rapid duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii.

Cryptococcosis is a life-threatening invasive fungal infection with significantly increasing mortality worldwide, which is mainly caused by Cryptococcus neoformans and Cryptococcus gattii. These two species complexes have different epidemiological and clinical characteristics, indicating the importance of accurate differential diagnosis. However, the clinically used culture method and cryptococcal capsular antigen detection couldn't achieve the above goals. Herein, we established a novel duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii within 1 hour. This assay combined the highly sensitive nucleic acid isothermal amplification and highly specific fluorescence probe method, which could effectively distinguish the sequence differences of the two species complexes using two different fluorescence flap probes in a single reaction system. This novel method showed excellent detection performance with sensitivity (10 copies/µL each) and specificity (100%) compared to traditional culture and sequencing methods. Furthermore, we applied this method to spiked clinical samples, 30 cerebrospinal fluids and 30 bronchoalveolar lavage fluids, which kept good detection performance. This novel rapid duplex flap probe-based isothermal assay is a promising and robust tool for applications in differential diagnosis of the Cryptococcus neoformans and Cryptococcus gattii in clinical settings, especially when clinical suspicion for cryptococcal disease is high and epidemiological studies.

Maize ZmLAZ1-3 gene negatively regulates drought tolerance in transgenic Arabidopsis.

BACKGROUND: Molecular mechanisms in response to drought stress are important for the genetic improvement of maize. In our previous study, nine ZmLAZ1 members were identified in the maize genome, but the function of ZmLAZ1 was largely unknown. RESULTS: The ZmLAZ1-3 gene was cloned from B73, and its drought-tolerant function was elucidated by expression analysis in transgenic Arabidopsis. The expression of ZmLAZ1-3 was upregulated by drought stress in different maize inbred lines. The driving activity of the ZmLAZ1-3 promoter was induced by drought stress and related to the abiotic stress-responsive elements such as MYB, MBS, and MYC. The results of subcellular localization indicated that the ZmLAZ1-3 protein localized on the plasma membrane and chloroplast. The ectopic expression of the ZmLAZ1-3 gene in Arabidopsis significantly reduced germination ratio and root length, decreased biomass, and relative water content, but increased relative electrical conductivity and malondialdehyde content under drought stress. Moreover, transcriptomics analysis showed that the differentially expressed genes between the transgenic lines and wild-type were mainly associated with response to abiotic stress and biotic stimulus, and related to pathways of hormone signal transduction, phenylpropanoid biosynthesis, mitogen-activated protein kinase signaling, and plant-pathogen interaction. CONCLUSION: The study suggests that the ZmLAZ1-3 gene is a negative regulator in regulating drought tolerance and can be used to improve maize drought tolerance via its silencing or knockout.

Flavonoids from the Aerial Parts of Sophora tonkinensis and Their Potential Anti-inflammatory Activities.

Four undescribed prenylated flavonoids, sophoratones A-D (1-4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC50 ranging from 19.91 ± 1.08 to 35.72 ± 2.92 µM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti-inflammatory agents.

Onset of Alzheimer disease in apolipoprotein ɛ4 carriers is earlier in butyrylcholinesterase K variant carriers.

BACKGROUND: The authors sought to examine the impact of the K-variant of butyrylcholinesterase (BCHE-K) carrier status on age-at-diagnosis of Alzheimer disease (AD) in APOE4 carriers. METHODS: Patients aged 50-74 years with cerebrospinal fluid (CSF) biomarker-confirmed AD, were recruited to clinical trial (NCT03186989 since June 14, 2017). Baseline demographics, disease characteristics, and biomarkers were evaluated in 45 patients according to BCHE-K and APOE4 allelic status in this post-hoc study. RESULTS: In APOE4 carriers (N = 33), the mean age-at-diagnosis of AD in BCHE-K carriers (n = 11) was 6.4 years earlier than in BCHE-K noncarriers (n = 22, P < .001, ANOVA). In APOE4 noncarriers (N = 12) there was no observed influence of BCHE-K. APOE4 carriers with BCHE-K also exhibited slightly higher amyloid and tau accumulations compared to BCHE-K noncarriers. A predominantly amyloid, limited tau, and limbic-amnestic phenotype was exemplified by APOE4 homozygotes with BCHE-K. In the overall population, multiple regression analyses demonstrated an association of amyloid accumulation with APOE4 carrier status (P < .029), larger total brain ventricle volume (P < .021), less synaptic injury (Ng, P < .001), and less tau pathophysiology (p-tau181, P < .005). In contrast, tau pathophysiology was associated with more neuroaxonal damage (NfL, P = .002), more synaptic injury (Ng, P < .001), and higher levels of glial activation (YKL-40, P = .01). CONCLUSION: These findings have implications for the genetic architecture of prognosis in early AD, not the genetics of susceptibility to AD. In patients with early AD aged less than 75 years, the mean age-at-diagnosis of AD in APOE4 carriers was reduced by over 6 years in BCHE-K carriers versus noncarriers. The functional status of glia may explain many of the effects of APOE4 and BCHE-K on the early AD phenotype. TRIAL REGISTRATION: NCT03186989 since June 14, 2017.

Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

Non-thyroidal disease syndrome in patients with systemic lupus erythematosus: relation to disease inflammatory activity.

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.

Reverse design of haptens based on antigen spatial conformation to prepare anti-capsaicinoids&gingerols antibodies for monitoring of gutter cooking oil.

Rapid simultaneous detection of multi-component adulteration markers can improve the accuracy of identification of gutter cooking oil in edible oil, which is made possible by broad-spectrum antibody (bs-mAb). This study used capsaicinoids (CPCs) and gingerol derivatives (GDs) as adulteration markers, and two broad-spectrum haptens (bs-haptens) were designed and synthesized based on a reverse design strategy of molecular docking. Electrostatic potential (ESP) and monoclonal antibodies (mAbs) preparation verified the strategy's feasibility. To further investigate the recognition mechanism, five other reported antigens and mAbs were also used. Finally, the optimal combination (Hapten 5-OVA/1-F12) and key functional groups (f-groups) were determined. The half maximal inhibitory concentration (IC50) for CPCs-GDs was between 88.13 and 499.16 ng/mL. Meanwhile, a preliminary lateral flow immunoassay (LFIA) study made practical monitoring possible. The study provided a theoretical basis for the virtual screening of bs-haptens and simultaneous immunoassay of multiple exogenous markers to monitor gutter oil rapidly and accurately.

Evaluating the depression state during perinatal period by non-invasive scalp EEG.

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.

Characterization and mechanism of simultaneous degradation of aflatoxin B1 and zearalenone by an edible fungus of Agrocybe cylindracea GC-Ac2.

Contamination with multiple mycotoxins is a major issue for global food safety and trade. This study focused on the degradation of aflatoxin B1 (AFB1) and zearalenone (ZEN) by 8 types of edible fungi belonging to 6 species, inclulding Agaricus bisporus, Agrocybe cylindracea, Cyclocybe cylindracea, Cyclocybe aegerita, Hypsizygus marmoreus and Lentinula edodes. Among these fungi, Agrocybe cylindracea strain GC-Ac2 was shown to be the most efficient in the degradation of AFB1 and ZEN. Under optimal degradation conditions (pH 6.0 and 37.4°C for 37.9 h), the degradation rate of both AFB1 and ZEN reached over 96%. Through the analysis of functional detoxification components, it was found that the removal of AFB1 and ZEN was primarily degraded by the culture supernatant of the fungus. The culture supernatant exhibited a maximum manganese peroxidase (MnP) activity of 2.37 U/mL. Interestingly, Agrocybe cylindracea strain GC-Ac2 also showed the capability to degrade other mycotoxins in laboratory-scale mushroom substrates, including 15A-deoxynivalenol, fumonisin B1, B2, B3, T-2 toxin, ochratoxin A, and sterigmatocystin. The mechanism of degradation of these mycotoxins was speculated to be catalyzed by a complex enzyme system, which include MnP and other ligninolytic enzymes. It is worth noting that Agrocybe cylindracea can degrade multiple mycotoxins and produce MnP, which is a novel and significant discovery. These results suggest that this candidate strain and its enzyme system are expected to become valuable biomaterials for the simultaneous degradation of multiple mycotoxins.

Astragaloside IV targeting autophagy of T cells improves inflammation of asthma.

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.

Effect of frailty on medication deviation during the hospital-family transition period in older patients with cardiovascular disease: An observational study.

Studies have shown that frailty increases cardiovascular disease (CVD) incidence in older patients and is associated with poor patient prognosis. However, the relationship between medication deviation (MD) and frailty remains unclear. This study aimed to explore the influence of frailty on MD during the hospital-family transition period among older patients with CVD. Between February 2022 and February 2023, 231 older people CVD patients were selected from a class III hospital in Nantong City using a multi-stage sampling method. A general information questionnaire was used to collect the socio-demographic characteristics of the participants prior to discharge, the frailty assessment scale was used to assess the participants frailty, and a medication deviation instrument was used to assess the participants MD on the 10th day after discharge. Propensity score matching was used to examine the effect of frailty on MD in older patients with CVD during the hospital-family transition period. The incidences of frailty and MD were 32.9% (76/231) and 75.8% (175/231), respectively. After propensity score matching, the risk of MD in frail patients with CVD was 4.978 times higher than that in non-frail patients with CVD (95% CI: [1.616, 15.340]; P = .005). Incidences of frailty and MD during the hospital-family transition period are high in older patients with CVD, and frailty has an impact on MD. Medical staff in the ward should comprehensively examine older patients with CVD for frailty and actively promote quality medication management during the hospital-family transition period to reduce MD occurrence and delay disease progression.

Study on the Mechanism of Levofloxacin Combined with Imipenem Against Pseudomonas aeruginosa.

Pseudomonas aeruginosa can develop resistance. Therefore, it is necessary to design proper treatment for it. Pseudomonas aeruginosa can develop resistance against levofloxacin due to the development of efflux pumps. However, the development of these efflux pumps cannot develop resistance against imipenem. Additionally, the MexCDOprJ efflux system which is responsible for the resistance of Pseudomonas aeruginosa to levofloxacin is highly susceptible to imipenem. The objective of the study was to evaluate the emergence of resistance of Pseudomonas aeruginosa against 750 mg levofloxacin, 250 mg imipenem, and a combination of 750 mg levofloxacin and 250 mg imipenem. An in vitro pharmacodynamic model was selected for the evaluation of the emergence of resistance. Pseudomonas aeruginosa strain 236, Pseudomonas aeruginosa strain GB2, and Pseudomonas aeruginosa strain GB65 were selected. Susceptibility testing of both antibiotics was done by agar dilution methodology. A disk diffusion bioassay was performed for antibiotics. RT-PCR measurement was done for the evaluation of expressions of Pseudomonas aeruginosa genes. Samples were tested at 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, and 30 h. Levofloxacin and imipenem both individually reported a decrease in colony-forming unit per milliliter of strength in the initial stage but in the later stage both develop resistance individually. Levofloxacin with imipenem had no resistance to Pseudomonas aeruginosa during 30 h. Time after the start of development of resistance or decrease in clinical efficacy was higher for levofloxacin and imipenem combination in all strains. The concentration of Pseudomonas aeruginosa at the time after the start of development of resistance or decrease in clinical efficacy was fewer for levofloxacin and imipenem combination. Levofloxacin with imipenem is recommended for the treatment of infection due to Pseudomonas aeruginosa.

Lysine-rich rice partially enhanced the growth and development of skeletal system with better skeletal microarchitecture in young rats.

Rice is the primary staple food for half of the world's population but is low in lysine content. Previously, we developed transgenic rice with enhanced free lysine content in rice seeds (lysine-rich rice), which was shown safe for consumption and improved the growth in rats. However, the effects of lysine-rich rice on skeletal growth and development remained unknown. In this study, we hypothesized that lysine-rich rice improved skeletal growth and development in weaning rats. Male weaning Sprague-Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various contents of lysine supplementation diet for 70 days. Bone microarchitectures were examined by microcomputed tomography, bone strength was investigated by mechanical test, and dynamics of bone growth were examined by histomorphometric analysis. In addition, we explored the molecular mechanism of lysine and skeletal growth through biochemical testing of growth hormone, bone turnover marker, and amino acid content of rat serum analysis, as well as in a cell culture system. Results indicated that the HFL diet improved rats' bone growth, strength, and microarchitecture compared with the WT diet group. In addition, the HFL diet increased the serum essential amino acids, growth hormone (insulin-like growth factor-1), and bone formation marker concentrations. The cell culture model showed that lysine deficiency reduced insulin-like growth factor-1 and Osterix expression, Akt/mammalian target of rapamycin signaling, and matrix mineralization, and inhibited osteoblast differentiation associated with bone growth. Our findings showed that lysine-rich rice improved skeletal growth and development in weaning rats. A further increase of rice lysine content is highly desirable to fully optimize bone growth and development.

Characterization of key bitter compounds in Idesia polycarpa var. vestita Diels fruit by sensory-guided fractionation.

Idesia polycarpa var. vestita Diels (I. vestita) has become a promising oil crop due to its easily digestible and highly nutritious fruit oil. However, the intense bitter taste of its fruit greatly limits its development and promotion in the food industry. Herein, five key bitter compounds from I. vestita fruit were isolated by sensory-guided fractionation and characterized using ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometer and nuclear magnetic resonance. The bitter taste of the identified compounds was subsequently validated by threshold tests and computational molecular docking. The bitterness threshold in water of idesin was the lowest (12.051 mg/L), and all bitter substances spontaneously bound to the bitter receptors hTAS2R16 and hTAS2R14, with a stronger affinity for the latter (approximately -6.5 - -9.0 kcal/mol). This is the first systematic study of bitter compounds in I. vestita fruit, providing a scientific basis for revealing the mechanism of bitterness formation and bitterness control.

Chromosomal-scale genomes of two Rosa species provide insights into genome evolution and ascorbate accumulation.

Rosa roxburghii and Rosa sterilis, two species belonging to the Rosaceae family, are widespread in the southwest of China. These species have gained recognition for their remarkable abundance of ascorbate in their fresh fruits, making them an ideal vitamin C resource. In this study, we generated two high-quality chromosome-scale genome assemblies for R. roxburghii and R. sterilis, with genome sizes of 504 and 981.2 Mb, respectively. Notably, we present a haplotype-resolved, chromosome-scale assembly for diploid R. sterilis. Our results indicated that R. sterilis originated from the hybridization of R. roxburghii and R. longicuspis. Genome analysis revealed the absence of recent whole-genome duplications in both species and identified a series of duplicated genes that possibly contributing to the accumulation of flavonoids. We identified two genes in the ascorbate synthesis pathway, GGP and GalLDH, that show signs of positive selection, along with high expression levels of GDP-d-mannose 3', 5'-epimerase (GME) and GDP-l-galactose phosphorylase (GGP) during fruit development. Furthermore, through co-expression network analysis, we identified key hub genes (MYB5 and bZIP) that likely regulate genes in the ascorbate synthesis pathway, promoting ascorbate biosynthesis. Additionally, we observed the expansion of terpene synthase genes in these two species and tissue expression patterns, suggesting their involvement in terpenoid biosynthesis. Our research provides valuable insights into genome evolution and the molecular basis of the high concentration of ascorbate in these two Rosa species.

Tanc1/2 TPR domain interacts with Myo18a C-terminus and undergoes liquid-liquid phase separation.

Tanc1 and its homologous protein Tanc2 are critical synaptic scaffold proteins which regulate synaptic spine densities and excitatory synapse strength. Recent studies indicated TANC1 and TANC2 are candidate genes of several neurodevelopmental disorders (NDDs). In this study, we identified and characterized a novel interaction between Tanc1/2 and Myo18a, mediated by the Tanc1/2 TPR domains and Myo18a coiled-coil domain and C-extension (CCex). Sequence analysis and size exclusion chromatography experiments reveal that high salt disrupts the interaction between Myo18a and Tanc1/2, indicating that the interaction is primarily driven by charge-charge interactions. More importantly, we found that the Tanc1-TPR/Myo18a CCex interaction could undergo liquid-liquid phase separation (LLPS) in both cultured cells and test tubes, which provides the biochemical basis and potential molecular mechanisms for the LLPS-mediated interactions between Myo18a and Tanc1/2.

Identification of SRSF10 as a promising prognostic biomarker with functional significance among SRSFs for glioma.

AIMS: The serine/arginine-rich splicing factor (SRSF) protein family members are essential mediators of the alternative splicing (AS) regulatory network, which is tightly implicated in cancer progression. However, the expression, clinical correlation, immune infiltration, and prognostic value of SRSFs in gliomas remain unclear. MATERIALS AND METHODS: Glioma samples were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Several databases, such as HPA, DAVID, UALCAN were used to comprehensively explore the roles of SRSFs. In addition, experimental validation of SRSF10 was also conducted. KEY FINDINGS: Here, we found the expression alterations of the SRSF family in glioma samples using data from the TCGA and CGGA_325 datasets. Among the 12 genes, most were found to be closely associated with glioma clinical features, which linked to poor prognosis in glioma patients. Interestingly, survival analysis identified only SRSF10 as a potential independent risk prognostic biomarker for glioma patients. Immune analysis indicated that glioma patients with high SRSF10 expression may respond well to immunotherapies targeting immune checkpoint (ICP) genes. Finally, knocking down SRSF10 reduced glioma cell viability, induced G1 cell cycle arrest, and induced the exclusion of bcl-2-associated transcription factor 1 (BCLAF1) exon 5a. SIGNIFICANCE: Overall, this study uncovers the oncogenic roles of most SRSF family members in glioma, with the exception of SRSF5, while highlighting SRSF10 as a potential novel independent prognostic biomarker for glioma.

RPLP2 activates TLR4 in an autocrine manner and promotes HIF-1α-induced metabolic reprogramming in hepatocellular carcinoma.

Metabolic reprogramming is a major feature of cancer, and aerobic glycolysis is one of the most widely studied metabolic reprogramming processes. Acidic ribosome protein P2 (RPLP2) is associated with both tumorigenesis and endoplasmic reticulum stress. However, limited knowledge exists regarding the role of RPLP2 in hepatocellular carcinoma (HCC) progression. In the present study, we observed a significant upregulation of RPLP2 in HCC tissues. Moreover, RPLP2 expression is closely correlated with patient prognosis and survival. The subsequent experimental validation demonstrated that RPLP2 exerted a regulatory effect on the expression of glycolytic enzymes and lactate production, thereby facilitating HCC cell proliferation. Mechanistically, the PI3K/AKT signalling pathway was found to play an important role in the regulation of hypoxia-inducible factor-1α (HIF-1α)-mediated aerobic glycolysis and cell growth. RPLP2 activates TLR4 on the surface of HCC cells and the downstream PI3K/AKT pathway through autocrine signalling. This activation then facilitates the entry of HIF-1α into the nucleus, enabling it to fulfil its transcriptional function. In conclusion, our findings suggested that RPLP2 induces a metabolic shift towards aerobic glycolysis and facilitates the progression of HCC through TLR4-dependent activation of the PI3K/AKT/HIF-1α pathway. Our study revealed the novel mechanism by which the ribosomal protein RPLP2 regulates glycolysis to promote HCC progression. These findings may offer a potential therapeutic target for HCC treatment.

Advances in methodologies of negative controls: a scoping review.

OBJECTIVES: Negative controls are considered an important tool to mitigate biases in observational studies. The aim of this scoping review was to summarize current methodologies of negative controls (both negative control exposure [NCE] and negative control outcome [NCO]). STUDY DESIGN AND SETTING: We searched PubMed, Web of Science, Embase, and Cochrane Library (up to March 9, 2023) for articles on methodologies of negative controls. Two reviewers selected eligible studies and collected relevant data independently and in duplicate. We reported total numbers and percentages, and summarized methodologies narratively. RESULTS: A total of 37 relevant methodological articles were included in our review. These publications covered NCE (n = 11, 29.8%), NCO (n = 13, 35.1%), or both (n = 13, 35.1%), with most focused on bias detection (n = 14, 37.8%), bias correction (n = 16, 43.3%), and P value or confidence interval (CI) calibration (n = 5, 13.5%). For the two remaining articles (5.4%), one discussed bias detection and P value or CI calibration and the other covered all the three functions. For bias detection, the existence of an association between the NCE (NCO) and outcome (exposure) variables of interest simply indicates that results may suffer from confounding bias, selection bias and/or information bias. For bias correction, however, the algorithms of negative control methods need more stringent assumptions such as rank preservation, monotonicity, and linearity. CONCLUSION: Negative controls can be leveraged for bias detection, P value or CI calibration, and bias correction, among which bias correction has been the most studied methodologically. The current available methods need some stringent assumptions to detect or remove bias. More methodological research is needed to optimize the use of negative controls.