Genome-wide characterization of LEA gene family reveals a positive role of BnaA.LEA6.a in freezing tolerance in rapeseed (Brassica napus L.).

BACKGROUND: Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). RESULTS: Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. CONCLUSION: This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.

The representation of contextual cue is stimulus-specific yet its expression is flexible.

Background: Contextual cueing refers to the phenomenon in which individuals utilize frequently encountered environmental contexts, comprised of distractors, as cues to expedite a target search. Due to the conflict between the widespread occurrence of contextual cue transfer and the observed impact of changing the identity of distractors on contextual cue learning, the content of contextual cue representations remains contentious. Considering the independent nature of contextual cue learning and expression, our proposition is twofold: (1) Contextual cue representations are stimulus-specific, and (2) their expression is highly flexible. Methods: To validate the model, two experiments were conducted. Experiment 1 aimed to confirm the hypothesis that contextual cue representations are stimulus-specific. We manipulated the identity consistency of distractors within repeated scenes during contextual cue learning. Difficulty in contextual cue learning under the identity-changing condition would suggest the necessity of identity within contextual cue representation, indicating the stimulus-specific nature of these representations. Experiment 2 was designed to affirm the conclusion of Experiment 1 and explore the flexibility in the expression of contextual cue representations. This experiment comprised two phases: learning and testing. During the learning phase, participants were exposed to two sets of repeated scenes in different colors under two learning conditions: load and no-load. Working memory load was introduced to interfere with the expression to prevent it from becoming automatic. In the subsequent testing phase, the colors of the two scene sets were interchanged to impede retrieval based on identity. If both load and no-load conditions demonstrate similar levels of contextual cue effects during the testing phase, it implies the flexibility in the expression of contextual cue representations and confirms the conclusion of Experiment 1. Results: In Experiment 1, a notable contextual cue learning effect was observed under the identity-consistent condition (p = 0.001). However, this effect was not evident under the identity-changing condition (p = 0.286). This finding strongly supports the stimulus-specific nature of contextual cue representation. In Experiment 2, the contextual cueing effect appeared but did not show a significant difference between the two conditions (t(23) = 0.02, p = 0.987, BF10 = 0.215), indicating the cognitive system's ability to flexibly redefine retrieval cues. This adaptability aligns with our hypothesis and confirms the high flexibility in the expression process of contextual cue representations and confirms the conclusion of Experiment 1.

Delta opioid peptide [D-ala2, D-leu5]-Enkephalin's ability to enhance mitophagy via TRPV4 to relieve ischemia/reperfusion injury in brain microvascular endothelial cells.

BACKGROUND: Local brain tissue can suffer from ischaemia/reperfusion (I/R) injury, which lead to vascular endothelial damage. The peptide δ opioid receptor (δOR) agonist [D-ala2, D-leu5]-Enkephalin (DADLE) can reduce apoptosis caused by acute I/R injury in brain microvascular endothelial cells (BMECs). OBJECTIVE: This study aims to explore the mechanism by which DADLE enhances the level of mitophagy in BMECs by upregulating the expression of transient receptor potential vanilloid subtype 4 (TRPV4). METHODS: BMECs were extracted and made to undergo oxygen-glucose deprivation/reoxygenation (OGD/R) accompanied by DADLE. RNA-seq analysis revealed that DADLE induced increased TRPV4 expression. The CCK-8 method was used to assess the cellular viability; quantitative PCR (qPCR) was used to determine the mRNA expression of Drp1; western blot was used to determine the expression of TRPV4 and autophagy-related proteins; and calcium imaging was used to detect the calcium influx. Autophagosomes in in the cells' mitochondria were observed by using transmission electron microscopy. ELISA was used to measure ATP content, and a JC-1 fluorescent probe was used to detect mitochondrial membrane potential. RESULTS: When compared with the OGD/R group, OGD/R+DADLE group showed significantly enhanced cellular viability; increased expression of TRPV4, Beclin-1, LC3-II/I, PINK1 and Parkin; decreased p62 expression; a marked rise in calcium influx; further increases in mitophagy, an increase in ATP synthesis and an elevation of mitochondrial membrane potential. These protective effects of DADLE can be blocked by a TRPV4 inhibitor HC067047 or RNAi of TRPV4. CONCLUSION: DADLE can promote mitophagy in BMECs through TRPV4, improving mitochondrial function and relieving I/R injury.

Study on plasma metabolomics profiling of depression in Chinese community-dwelling older adults based on untargeted LC/GC‒MS.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways.

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway.

BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. METHODS: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-ß1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1ß in combination with TGF-ß1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. RESULTS: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-ß1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. CONCLUSION: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice. Methods: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality. Results: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs. Conclusion: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

Passive eDNA sampling facilitates biodiversity monitoring and rare species detection.

Environmental DNA (eDNA) technology has revolutionized biomonitoring, but challenges remain regarding water sample processing. The passive eDNA sampler (PEDS) represents a viable alternative to active, water filtration-based eDNA enrichment methods, but the effectiveness of PEDS for surveying biodiverse and complex natural water bodies is unknown. Here, we collected eDNA using filtration and glass fiber filter-based PEDS (submerged in water for 1 d) from 27 sites along the final reach of the Yangtze River and the coast of the Yellow Sea, followed by eDNA metabarcoding analysis of fish biodiversity and quantitative PCR (qPCR) for a critically endangered aquatic mammal, the Yangtze finless porpoise. We ultimately detected 98 fish species via eDNA metabarcoding. Both eDNA sampling methods captured comparable local species richness and revealed largely similar spatial variation in fish assemblages and community partitions between the river and sea sites. Notably, the Yangtze finless porpoise was detected only in the metabarcoding of eDNA collected by PEDS at five sites. Also, species-specific qPCR revealed that the PEDS captured porpoise eDNA at more sites (7 vs. 2), in greater quantities, and with a higher detection probability (0.803 vs. 0.407) than did filtration. Our results demonstrate the capacity of PEDS for surveying fish biodiversity, and support that continuous eDNA collection by PEDS can be more effective than instantaneous water sampling at capturing low abundance and ephemeral species in natural waters. Thus, the PEDS approach can facilitate more efficient and convenient eDNA-based biodiversity surveillance and rare species detection.

A comprehensive meta-analysis and systematic review of breath analysis in detection of COVID-19 through Volatile organic compounds.

BACKGROUND: The COVID-19 pandemic had profound global impacts on daily lives, economic stability, and healthcare systems. Diagnosis of COVID-19 infection via RT-PCR was crucial in reducing spread of disease and informing treatment management. While RT-PCR is a key diagnostic test, there is room for improvement in the development of diagnostic criteria. Identification of volatile organic compounds (VOCs) in exhaled breath provides a fast, reliable, and economically favorable alternative for disease detection. METHODS: This meta-analysis analyzed the diagnostic performance of VOC-based breath analysis in detection of COVID-19 infection. A systematic review of twenty-nine papers using the grading criteria from Newcastle-Ottawa Scale (NOS) and PRISMA guidelines was conducted. RESULTS: The cumulative results showed a sensitivity of 0.92 (95 % CI, 90 %-95 %) and a specificity of 0.90 (95 % CI 87 %-93 %). Subgroup analysis by variant demonstrated strong sensitivity to the original strain compared to the Omicron and Delta variant in detection of SARS-CoV-2 infection. An additional subgroup analysis of detection methods showed eNose technology had the highest sensitivity when compared to GC-MS, GC-IMS, and high sensitivity-MS. CONCLUSION: Overall, these results support the use of breath analysis as a new detection method of COVID-19 infection.

Pituitary-related immune adverse events induced by programmed death Protein-1 inhibitors differ clinically from hypophysitis.

OBJECTIVE: We aimed to elucidate the clinical features of pituitary immune-related adverse events (irAEs) induced by PD-1 inhibitors in a Chinese cohort and the previous literatures. PATIENTS AND DESIGN AND MEASUREMENTS: We retrospectively analysed the clinical manifestations, laboratory examination findings, imaging features and treatments of 14 patients with pituitary irAEs caused by PD-1 inhibitors in our cohort. In addition, we searched PubMed for all English articles on pituitary irAEs induced by PD-1 inhibitors published from 1950 to 2023. A total of 47 articles were included, and the clinical characteristics of 94 patients with pituitary irAEs induced by PD-1 inhibitors in these literatures were compared to the characteristics of our cohort. RESULTS: Among the 14 patients in our cohort with pituitary irAEs induced by PD-1 inhibitors, 12 patients (85.71%, 12/14) exhibited isolated ACTH deficiency (IAD), 100.0% (14/14) of the central adrenocortical insufficiency, and 2 patients showed more than one hypothalamic-pituitary axis injury (14.29%, 2/14). Pituitary magnetic resonance imaging in all the 14 patients showed no pituitary enlargement. In previous studies we reviewed, 82.98% of the total (78/94) presented with pituitary irAEs as IAD, 100.0% (94/94) of the central adrenocortical insufficiency, and 78.33% of the patients showed no abnormality of the pituitary gland (47/60). The pituitary irAEs caused by PD-1 inhibitors did not involve typical manifestations of hypophysitis, such as pituitary enlargement, headache, visual field defects, and multiple pituitary function impairments in our cohort and the previous literatures. CONCLUSION: In our study, pituitary immune-related adverse reactions induced by PD-1 inhibitors mainly manifested isolated ACTH deficiency rather than hypophysitis.

CircUGGT2 downregulation by METTL14-dependent m6A modification suppresses gastric cancer progression and cisplatin resistance through interaction with miR-186-3p/MAP3K9 axis.

Chemoresistance is a major therapeutic challenge in advanced gastric cancer (GC). N6-methyladenosine (m6A) RNA modification has been shown to play fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to GC and chemoresistance remain unknown. We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. The expression of circUGGT2 was markedly increased in cisplatin (DDP)-resistant GC cells. CircUGGT2 KD impaired cell growth, metastasis and DDP-resistance in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186-3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186-3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186-3p expression and harbored a poor prognosis in patients with GC. Our findings unveil that METTL14-dependent m6A modification of circUGGT2 inhibits GC progression and DDP resistance by regulating miR-186-3p/MAP3K9 axis.

Comparative Transcriptomics Uncovers Upstream Factors Regulating BnFAD3 Expression and Affecting Linolenic Acid Biosynthesis in Yellow-Seeded Rapeseed (Brassica napus L.).

α-Linolenic acid (ALA) is an important nutrient component in rapeseed oil, and rapeseed breeders want to either restrain or enhance the function of fatty acid desaturases (FADs) in the ALA biosynthesis pathway. To determine the reason for the upregulation of rapeseed BnFAD genes in two high-ALA accessions, R8Q10 and YH25005, we compared their transcriptome profiles in the seed at 24 days after pollination (DAP) with those of two low-ALA lines, A28 and SW. The expression levels of twenty-eight important genes in the seed samples at 20, 27, and 34 DAP were also investigated using an RT-qPCR. The expression levels of genes involved in flavonoid and proanthocyanidin synthesis, including BnCHS, BnCHI, BnDFR, BnFLS1, BnLDOX, BnBAN, BnTT10, and BnTT12 and genes encoding the transcription factors BnTT1, BnTT2, BnTT8, and BnTT16 were lower in R8Q10 and YH25005 than in A28 and SW. The expression levels of genes encoding master transcription factors in embryo development, such as BnLEC1, BnABI3, BnFUS3, BnL1L, BnAREB3, and BnbZIP67, were elevated significantly in the two high-ALA accessions. Combined with previous results in the Arabidopsis and rapeseed literature, we speculated that the yellow-seededness genes could elevate the activity of BnLEC1, BnABI3, BnFUS3, and BnbZIP67, etc., by reducing the expression levels of several transparent testa homologs, resulting in BnFAD3 and BnFAD7 upregulation and the acceleration of ALA synthesis. Yellow-seededness is a favorable factor to promote ALA synthesis in the two high-ALA accessions with the yellow-seeded trait. These findings provide initial insights into the transcriptomic differences between high-/low-ALA germplasms and a theoretic basis for seed quality breeding.

Sparsified federated learning with differential privacy for intrusion detection in VANETs based on Fisher Information Matrix.

With the continuous development of vehicular ad hoc networks (VANET) security, using federated learning (FL) to deploy intrusion detection models in VANET has attracted considerable attention. Compared to conventional centralized learning, FL retains local training private data, thus protecting privacy. However, sensitive information about the training data can still be inferred from the shared model parameters in FL. Differential privacy (DP) is sophisticated technique to mitigate such attacks. A key challenge of implementing DP in FL is that non-selectively adding DP noise can adversely affect model accuracy, while having many perturbed parameters also increases privacy budget consumption and communication costs for detection models. To address this challenge, we propose FFIDS, a FL algorithm integrating model parameter pruning with differential privacy. It employs a parameter pruning technique based on the Fisher Information Matrix to reduce the privacy budget consumption per iteration while ensuring no accuracy loss. Specifically, FFIDS evaluates parameter importance and prunes unimportant parameters to generate compact sub-models, while recording the positions of parameters in each sub-model. This not only reduces model size to lower communication costs, but also maintains accuracy stability. DP noise is then added to the sub-models. By not perturbing unimportant parameters, more budget can be reserved to retain important parameters for more iterations. Finally, the server can promptly recover the sub-models using the parameter position information and complete aggregation. Extensive experiments on two public datasets and two F2MD simulation datasets have validated the utility and superior performance of the FFIDS algorithm.

Rapid room-temperature phosphorescence chiral recognition of natural amino acids.

Chiral recognition of amino acids is very important in both chemical and life sciences. Although chiral recognition with luminescence has many advantages such as being inexpensive, it is usually slow and lacks generality as the recognition module relies on structural complementarity. Here, we show that one single molecular-solid sensor, L-phenylalanine derived benzamide, can manifest the structural difference between the natural, left-handed amino acid and its right-handed counterpart via the difference of room-temperature phosphorescence (RTP) irrespective of the specific chemical structure. To realize rapid and reliable sensing, the doped samples are obtained as nanocrystals from evaporation of the tetrahydrofuran solutions, which allows for efficient triplet-triplet energy transfer to the chiral analytes generated in situ from chiral amino acids. The results show that L-analytes induce strong RTP, whereas the unnatural D-analytes produce barely any afterglow. The method expands the scope of luminescence chiral sensing by lessening the requirement for specific molecular structures.

MicroRNA­373­3p inhibits the proliferation and invasion of non­small­cell lung cancer cells by targeting the GAB2/PI3K/AKT pathway.

MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Behind the wheel: exploring gray matter variations in experienced drivers.

Background: Driving is a complex skill involving various cognitive activities. Previous research has explored differences in the brain structures related to the navigational abilities of drivers compared to non-drivers. However, it remains unclear whether changes occur in the structures associated with low-level sensory and higher-order cognitive abilities in drivers. Methods: Gray matter volume, assessed via voxel-based morphometry analysis of T1-weighted images, is considered a reliable indicator of structural changes in the brain. This study employs voxel-based morphological analysis to investigate structural differences between drivers (n = 22) and non-drivers (n = 20). Results: The results indicate that, in comparison to non-drivers, drivers exhibit significantly reduced gray matter volume in the middle occipital gyrus, middle temporal gyrus, supramarginal gyrus, and cerebellum, suggesting a relationship with driving-related experience. Furthermore, the volume of the middle occipital gyrus, and middle temporal gyrus, is found to be marginally negative related to the years of driving experience, suggesting a potential impact of driving experience on gray matter volume. However, no significant correlations were observed between driving experiences and frontal gray matter volume. Conclusion: These findings suggest that driving skills and experience have a pronounced impact on the cortical areas responsible for low-level sensory and motor processing. Meanwhile, the influence on cortical areas associated with higher-order cognitive function appears to be minimal.

Comprehensive geriatric assessment of older patients with renal disease: a cross-sectional survey.

Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.

[Effects of Personalized Exercise Prescriptions on Sarcopenia in Patients Undergoing Hemodialysis].

Sarcopenia is a major factor affecting the health and quality of life of the patients undergoing hemodialysis.Exercise can effectively ameliorate sarcopenia in these patients.However,the type,intensity,time,and frequency of exercise influence the effect of exercise.This review describes the effects of different exercise prescriptions on sarcopenia in the patients undergoing hemodialysis.It aims to assist medical staff in developing personalized exercise prescriptions,guiding patients to engage in exercise,and provide effective strategies for the prevention and treatment of sarcopenia in the patients undergoing hemodialysis.

[Research Progress in Pathogenesis,Nutrition and Exercise Intervention of Patients With Protein Energy Wasting].

Protein energy wasting(PEW)is common in maintenance hemodialysis(MHD)patients,and it is associated with a variety of adverse clinical outcomes,including weight loss and increased protein catabolism.There are many studies on health interventions for MHD patients through nutrition strategies,exercise patterns and the combination of both.This article reviews the pathogenesis,diagnostic criteria and intervention measures of PEW,aiming to provide a reference for early clinical diagnosis,identification and intervention of PEW.