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ObjectiveThe aim of this study was to evaluate the admission indicators and characteristics of individuals diagnosed with type 1 diabetes (T1D) to ascertain potential impact on the choice of glucose control therapy after discharge.MethodsA total of 398 eligible T1D patients were selected. We conducted multivariable logistic regression analysis to determine the independent influence of predictors on the selection of glucose control therapy after discharge. To explore the influencing factors of different subgroups, we additionally performed subgroup analyses based on gender and age.ResultsOur study revealed that body mass index (BMI) was noteworthy influence factor for prescription of insulin and non-insulin antidiabetic drug (NIAD prescription) in T1D patients of general population [OR = 1.109 (1.033-1.195), p = 0.006], male [OR = 1.166 (1.040−1.318), p = 0.011] and individuals below the age of 30 years [OR = 1.146 (1.020−1.301), p = 0.028]. Diastolic blood pressure (DBP) was a protective factor for NIAD prescription in the general population [OR = 0.971 (0.949-0.992), p = 0.008] and women [OR = 0.955 (0.923−0.988), p = 0.008]. The other risk factor of NIAD prescription in men was dyslipidemia [OR = 4.824 (1.442−22.246), p = 0.020]. Pulse pressure [OR = 1.036 (1.007–1.068), p = 0.016] constituted an additional risk factor of NIAD prescription among individuals below the age of 30 years. The risk factors of NIAD prescription for people aged 30 to 50 years were length of stay [OR = 1.097 (1.014–1.196), p = 0.026] and initial blood glucose [OR = 1.078 (1.007–1.168), p = 0.047]. In the case of individuals aged above 50 years, physicians exhibited a higher tendency to prescribe supplementary non-insulin medications to men [OR = 9.385 (1.501–87.789), p = 0.029].ConclusionsWe identified notable factors that influence discharge prescriptions in patients with T1D. In order to enhance the treatment outcome for the patient, clinicians ought to have a special focus on these indicators or factors.

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn’t impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

Background and objectiveOur group has developed a novel artificial cervical joint complex (ACJC) as a motion preservation instrument for cervical corpectomy procedures. Through finite element analysis (FEA), this study aims to assess this prosthesis’s mobility and stability in the context of physiological reconstruction of the cervical spine.Materials and methodsA finite element (FE)model of the subaxial cervical spine (C3-C7) was established and validated. ACJC arthroplasty, anterior cervical corpectomy and fusion (ACCF), and two-level cervical disc arthroplasty (CDA) were performed at C4-C6. Range of motion (ROM), intervertebral disc pressure (IDP), facet joint stress (FJS), and maximum von Mises stress on the prosthesis and vertebrae during loading were compared.ResultsCompared to the intact model, the ROM in all three surgical groups demonstrated a decline, with the ACCF group exhibiting the most significant mobility loss, and the highest compensatory motion in adjacent segments. ACJC and artificial cervical disc prosthesis (ACDP) well-preserved cervical mobility. In the ACCF model, IDP and FJS in adjacent segments increased notably, whereas the index segments experienced the most significant FJS elevation in the CDA model. The ROM, IDP, and FJS in both index and adjacent segments of the ACJC model were intermediate between the other two. Stress distribution of ACCF instruments and ACJC prosthesis during the loading process was more dispersed, resulting in less impact on the adjacent vertebrae than in the CDA model.ConclusionThe biomechanical properties of the novel ACJC were comparable to the ACCF in constructing postoperative stability and equally preserved physiological mobility of the cervical spine as CDA without much impact on adjacent segments and facet joints. Thus, the novel ACJC effectively balanced postoperative stability with cervical motion preservation.

IntroductionPorcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood.MethodsThis study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected.Results and discussionWe found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.

IntroductionFirefighters are exposed to polycyclic aromatic hydrocarbons (PAHs) during fire suppression, but the extent of PAH penetration through turnout gear and its impact on blood cell components remains uncertain. The main objective of this study is to investigate the residual levels of PAHs on turnout gear and skin, and to assess their potential effects on blood cell components in firefighters. We hypothesize that firefighting activities lead to increased PAH exposure, which in turn may induce alterations in blood cell composition. We also hypothesize that differences in PAH exposure and corresponding blood cell changes will be observed between volunteer and career firefighters.MethodsForty-seven firefighters were recruited from 11 fire departments in Oklahoma. PAH levels on gear and skin were measured, and complete blood count (CBC) parameters were analyzed. Parametric and non-parametric tests were used to examine differences in PAH exposures and hematological profiles between volunteer and career firefighters and possible changes over time. Generalized estimating equation (GEE) models were performed to assess the relationships between PAHs and blood cells.ResultsOur analysis revealed significant hematological differences between volunteer and career firefighters, with volunteers exhibiting lower aerobic capacity and higher systemic inflammation. Increased levels of specific PAHs were found on volunteers' gear post-fire.ConclusionOur findings indicate an association between PAH exposure and changes in blood parameters, emphasizing the need for improved decontamination protocols and protective measures, particularly for volunteer firefighters.

BackgroundCervical cancer is primarily caused by HPV infection. The epidemiology of HPV infection in specific areas is of great meaning of guide cervical cancer screening and formulating HPV vaccination strategies. Here, we evaluated the epidemiological characteristics of HPV infection in Xiamen population.MethodsIn total, 159,049 cervical exfoliated cell samples collected from female outpatients in Women and Children’s Hospital, School of Medicine, Xiamen between January 2013 and July 2023 were analyzed. HPV DNA detection was performed using HPV genotyping kits (Hybribio Limited Corp, China). An analysis was conducted on the prevalence of HPV infection, taking into account factors such as age, year, and multiple patterns of HPV infection. The differences in prevalence among age groups and years were compared using χ2 test.ResultsThe overall prevalence of any 21 HPV genotypes was 18.4%, of which the high-risk HPV (HR-HPV) positive rate was 14.6%. The age-specific prevalence of HPV infection showed a bimodal distribution, with two distinct peaks, one at

This study delves into the protective mechanisms of Icariin (ICA) against cisplatin-induced damage in Madin-Darby canine kidney (MDCK) cells. Comprising two distinct phases, the investigation initially employed a single-factor randomized design to ascertain the minimal cisplatin concentration eliciting MDCK cell damage, spanning concentrations from 0 to 16 mmol/L. Concurrently, various concentrations of ICA (ranging from 5 to 50 mmol/L) were combined with 1 mmol/L cisplatin to determine the most efficacious treatment concentration. Subsequent investigations utilized four treatment groups: control, 1 mmol/L cisplatin, 1 mmol/L cisplatin + 20 mmol/L ICA, and 1 mmol/L cisplatin + 25 mmol/L ICA, aimed at elucidating ICA's protective mechanisms. Findings from the initial phase underscored a significant reduction in MDCK cell viability with 1 mmol/L cisplatin in comparison to the control (P < 0.01). Notably, the inclusion of 20 and 25 mmol/L ICA substantively ameliorated MDCK cell viability under 1 mmol/L cisplatin (P < 0.01). Moreover, cisplatin administration induced an elevation in inflammatory factors, malondialdehyde (MDA), reactive oxygen species (ROS), and Bax protein levels, while concurrently suppressing superoxide dismutase (SOD), catalase (CAT), and Bcl-2 expression (P < 0.01). Conversely, supplementation of 20 and 25 mmol/L ICA demonstrated a marked increase in mitochondrial membrane potential and levels of SOD, CAT, and Bcl-2 (P < 0.01). These interventions effectively attenuated inflammatory responses and suppressed Bax protein expression (P < 0.05), consequently mitigating cisplatin-induced apoptosis in MDCK cells (P < 0.01). In summary, these findings elucidate the role of ICA in impeding apoptosis in cisplatin-induced MDCK cells by regulating inflammatory responses, oxidative stress, and autophagic protein expression.

Background and purposeTo establish and validate a hybrid radiomics model to predict overall survival in cervical cancer patients receiving concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively collected 367 cervical cancer patients receiving chemoradiotherapy from the First Affiliated Hospital of Soochow University in China and divided them into a training set and a test set in a ratio of 7:3. Handcrafted and deep learning (DL)-based radiomics features were extracted from the contrast-enhanced computed tomography (CT), and the two types of radiomics signatures were calculated based on the features selected using the least absolute shrinkage and selection operator (LASSO) Cox regression. A hybrid radiomics nomogram was constructed by integrating independent clinical risk factors, handcrafted radiomics signature, and DL-based radiomics signature in the training set and was validated in the test set.ResultsThe hybrid radiomics nomogram exhibited favorable performance in predicting overall survival, with areas under the receiver operating characteristic curve (AUCs) for 1, 3, and 5 years in the training set of 0.833, 0.777, and 0.871, respectively, and in the test set of 0.811, 0.713, and 0.730, respectively. Furthermore, the hybrid radiomics nomogram outperformed the single clinical model, handcrafted radiomics signature, and DL-based radiomics signature in both the training (C-index: 0.793) and test sets (C-index: 0.721). The calibration curves and decision curve analysis (DCA) indicated that our hybrid nomogram had good calibration and clinical benefits. Finally, our hybrid nomogram demonstrated value in stratifying patients into high- and low-risk groups (cutoff value: 5.6).ConclusionA high-performance hybrid radiomics model based on pre-radiotherapy CT was established, presenting strengths in risk stratification.

Background: There is an inconsistent association between overweight/obesity and chronic obstructive pulmonary disease (COPD). Considering that different metabolic characteristics exist among individuals in the same body mass index (BMI) category, the classification of overweight/obesity based on metabolic status may facilitate the risk assessment of COPD. Our study aimed to explore the relationship between metabolic overweight/obesity phenotypes and unplanned readmission in patients with COPD.Methods: We conducted a retrospective cohort study using the Nationwide Readmissions Database (NRD). According to metabolic overweight/obesity phenotypes, patients were classified into four groups: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy with overweight/obesity (MHO), and metabolically unhealthy with overweight/obesity (MUO). The primary outcome was unplanned readmission to hospital within 30 days of discharge from index hospitalization. Secondary outcomes included in-hospital mortality, length of stay (LOS) and total charges of readmission within 30 days.Results: Among 1,445,890 patients admitted with COPD, 167,156 individuals were unplanned readmitted within 30 days. Patients with the phenotype MUNO [hazard ratio (HR), 1.049; 95%CI, 1.038–1.061; p < 0.001] and MUO (HR, 1.061; 95%CI, 1.045–1.077; p < 0.001) had a higher readmission risk compared with patients with MHNO. But in elders (≥65yr), MHO also had a higher readmission risk (HR, 1.032; 95%CI, 1.002–1.063; p = 0.039). Besides, the readmission risk of COPD patients with hyperglycemia or hypertension regardless of overweight/obesity increased (p < 0.001).Conclusion: In patients with COPD, overweight/obesity alone had little effect on unplanned readmission, whereas metabolic abnormalities regardless of overweight/obesity were associated with an increased risk of unplanned readmission. Among the metabolic abnormalities, particular attention should be paid to hyperglycemia and hypertension. But in elders (≥65yr) overweight/obesity and metabolic abnormalities independently exacerbated the adverse outcomes.

PurposeFrailty is a difficult-to-measure condition that is susceptible to adverse outcomes. The Japan Frailty Scale (JFS) is a tool for assessing frailty status in older adults. This study aimed to translate and culturally adapt the JFS into a Chinese version (JFS-C).Materials and methodsThe study included 160 older adults as participants. Internal consistency was assessed using Cronbach’s alpha, and test–retest reliability was conducted using the intraclass correlation coefficient (ICC). Convergent validity was evaluated by assessing the correlation between JFS-C and the Barthel Index, the Frail scale, and the 36-item Short-Form Health Survey (SF-36). Criterion validity was assessed by comparing JFS-C scores with the Frail scale.ResultsJFS-C demonstrated adequate internal consistency (Cronbach’s alphas = 0.711) and excellent test–retest reliability over a 7 to 10-day interval (ICC = 0.949). Correlation analysis showed a strong positive correlation between JFS-C and the Frail scale (r = 0.786, p

This paper presents a method to investigate the impact of centralized and distributed renewable energy on the power grid system, aiming to discern their differences. First, we derived the coupling relationship between renewable energy permeability and access point voltage under a simplified model. Second, we proposed a holomorphic embedding model designed for non-global variation, enabling the construction of the bus state trajectory index. This index is employed to analyze the influence of centralized and distributed renewable energy access on power grid stability and voltage under low-permeability conditions. Furthermore, under high permeability, we determined the limit permeability of centralized and distributed renewable energy. Last, we provided renewable energy configuration recommendations to enhance the system’s receptive capacity.

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

The shield machine is clogged frequently when tunneling in cohesive strata. Shield clogging is closely linked to the shear strength exhibited at the clay-metal interface. To investigate the impact of anti-sticking coating technology on the shear strength at the clay-metal interface, a series of direct shear tests were conducted. The obtained test results revealed an initial increase in shear stress at the clay-metal interface as shear displacement increased, eventually reaching a state of stabilization. The shear strength exhibited a gradual increase initially, followed by a significant increase, and eventually reached a plateau with the rise in the consistency index. It was observed that the adhesion between the anti-adhesion coating and clay was relatively weak, but the presence of the anti-adhesion coating effectively reduced the risk of shield clogging.

As a class of short non-coding ribonucleic acids (RNAs), microRNAs (miRNA) regulate gene expression in human cells and are expected to be nucleic acid drugs to regulate and treat a variety of biological processes and diseases. However, the issues with potential materials toxicity, quantity production, poor cellular uptake, and endosomal entrapment limit their further applications in clinical practice. Herein, ZIF-8, a metal-organic framework with noncytotoxic zinc (II) as the metal coordination center, was selected as miRNA delivery vector was used to prepare miR-200c-3p@ZIF-8 in one step by Y-shape microfluidic chip to achieve intracellular release with low toxicity, batch size, and efficient cellular uptake. The obtained miR-200c-3p@ZIF-8 was identified by TEM, particle size analysis, XRD, XPS, and zeta potential. Compared with the traditional hydrothermal method, the encapsulation efficiency of miR-200c-3p@ZIF-8 prepared by the microfluidic method is higher, and the particle size is more uniform and controllable. The experimental results in cellular level verified that the ZIF-8 vectors with low cytotoxicity and high miRNAs loading efficiency could significantly improve cellular uptake and endosomal escape of miRNAs, providing a robust and general strategy for nucleic acid drug delivery. As a model, the prepared miR-200c-3p@ZIF-8 is confirmed to be effective in osteoarthritis treatment.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent and treat AAD by providing the gut barrier and restoring the gut microflora. This study will overview the Systematic Reviews (SRs) of probiotics in preventing and treating AAD in children. It will also assess the reporting, methodological, and evidence quality of the included SRs to provide evidence for their clinical practice.Methods: After searching PubMed, Embase, Cochrane Library, CNKI, CBM, VIP, and WanFang Data databases, and finally included SRs of probiotics in the prevention and treatment of AAD in children, which were published before 1 October 2022. The reporting, methodological, and evidence quality of the included SRs were assessed by PRISMA 2020 statement, AMSTAR 2 tool, and GRADE system.Results: A total of 20 SRs were included, and the results of PRISMA 2020 showed that 4 out of 20 SRs with relatively complete reporting, and the others within some reporting deficiencies, with scores ranging from 17 points to 26.5 points; the results of AMSTAR 2 showed that 3 SRs belonged to moderate quality level, 10 SRs belonged to low-quality level and 7 SRs being extremely low-quality level; the results of the GRADE system showed that a total of 47 outcomes were reported for the included SRs, three were high-level evidence quality, 16 were medium-level evidence quality, 24 were low-level evidence quality, and four were extremely low-level evidence quality; the results of the Meta-analysis showed that high doses (5–40 billion CFUs per day) of probiotics had a significant effect in the prevention of AAD, but it is too early to conclude the effectiveness and safety of other probiotic drugs for AAD in children, except for Lacticaseibacillus rhamnosus and Saccharomyces boulardii.Conclusion: Current evidence shows that probiotics effectively prevent and treat AAD in children, and the effect of probiotics on pediatric AAD may be a potential dose-response effect. However, the conclusion should be treated with caution due to deficiencies in the methodological, reporting, and evidence quality of the included SRs. Therefore, the methodological, reporting, and evidence quality of relevant SRs still need further improvement.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022362328

Correct usage and maintenance of the enteral nutrition feeding pump system is always a challenge in nutrition support for patients with colorectal cancer (CRC). However, there are few studies on the sustained accuracy improvement of the enteral nutrition feeding system in discharged CRC patients. Here, we established a seven-month quality control circle (QCC) activity with the theme of improving the performance of home enteral feeding pumps (EFP) and examined the effect of QCC activity on the nutritional state and quality of life in discharged CRC patients. We enrolled 100 discharged CRC patients treated with home enteral nutrition from Zhejiang Cancer Hospital between March 2020 and December 2021. The patients were randomly split into two research groups: one participated in the QCC activity (n = 50) and the other did not (n = 50). QCC analysis indicated that the top 3 causes of EFP inaccurate usage are the simple and boring contents of training, various types of pumps, no examination rules, and lack of management. Furthermore, both intra- and inter-group comparisons showed that QCC significantly improved the patients’ pass rate of nutrition pump operation from 52 to 70% after 1-month of activity, which gradually improved and got the highest (90%) after 3 months (p

RationaleA family of short synthetic, triphosphorylated stem-loop RNAs (SLRs) have been designed to activate the retinoic-acid-inducible gene I (RIG-I) pathway and induce a potent interferon (IFN) response, which may have therapeutic potential. We investigated immune response modulation by SLR10. We addressed whether RIG-I pathway activation with SLR10 leads to protection of nonsmoking (NS) and cigarette smoke (CS)-exposed mice after influenza A virus (IAV) infection.MethodsMice were given 25 µg of SLR10 1 day before IAV infection. We compared the survival rates and host immune responses of NS and CS-exposed mice following challenge with IAV.ResultsSLR10 significantly decreased weight loss and increased survival rates in both NS and CS-exposed mice during IAV infection. SLR10 administration repaired the impaired proinflammatory response in CS-exposed mice without causing more lung injury in NS mice as assessed by physiologic measurements. Although histopathologic study revealed that SLR10 administration was likely to result in higher pathological scores than untreated groups in both NS and CS mice, this change was not enough to increase lung injury evaluated by lung-to-body weight ratio. Both qRT-PCR on lung tissues and multiplex immunoassay on bronchoalveolar lavage fluids (BALFs) showed that most IFNs and proinflammatory cytokines were expressed at lower levels in SLR10-treated NS mice than control-treaded NS mice at day 5 post infection (p.i.). Remarkably, proinflammatory cytokines IL-6, IL-12, and GM-CSF were increased in CS-exposed mice by SLR10 at day 5 p.i. Significantly, SLR10 elevated the ratio of the two chemokines (CXCL9 and CCL17) in BALFs, suggesting macrophages were polarized to classically activated (M1) status. In vitro testing also found that SLR10 not only stimulated human alveolar macrophage polarization to an M1 phenotype, but also reversed cigarette smoke extract (CSE)-induced M2 to M1 polarization.ConclusionsOur data show that SLR10 administration in mice is protective for both NS and CS-exposed IAV-infected mice. Mechanistically, SLR10 treatment promoted M1 macrophage polarization in the lung during influenza infection. The protective effects by SLR10 may be a promising intervention for therapy for infections with viruses, particularly those with CS-enhanced susceptibility to adverse outcomes.

Marigold can protect crops against soil-borne diseases. However, the effects of intercropping with marigold on apple rhizosphere soils are not known. In this study, we investigated the metabolite profiles and bacterial community structures in rhizosphere soils of the apple-marigold intercropping system by high-throughput sequencing and soil metabolomics. The results show that intercropping marigold could significantly enhance soil moisture, nitrogen, and enzyme activities compared with clean tillage. The soil metabolite profiles and the soil bacterial community structures in the rhizosphere soils were different between the inter-and mono-cropping systems. Among nine metabolites, carbohydrates were more increased in the intercropping system than in the monocropping system. Pathway enrichment analysis revealed that the greatest differential, in terms of metabolic pathway, was starch and sucrose metabolism. Moreover, intercropping marigold significantly increased the relative abundance of plant growth promoting bacteria in rhizosphere soils, such as Rhizobiales, Pseudomonadales, and Bacillales. These results indicate that marigold intercropping positively affected the apple orchard’s soil quality and may provide a new intercropping technique to improve soil fertility in orchards and promote plant growth.

Background and aimsMitogen-activated protein kinases (MAPKs) have been reported to respond to various stimuli including heat stress. This research aimed to investigate whether StMAPK1 is implicated in the transduction of the heat stress signal to adapt heat stress as a thermos-tolerant gene.Materials and methodsPotato plants were cultivated under mild (30°C) and acute (35°C) heat stress conditions to analyze mRNA expression of StMAPKs and physiological indicators. StMAPK1 was up-regulated and down-regulated by transfection. Subcellular localization of StMAPK1 protein was observed by fluorescence microscope. The transgenic potato plants were assayed for physiological indexes, photosynthesis, cellular membrane integrity, and heat stress response gene expression.ResultsHeat stress altered the expression prolife of StMAPKs. StMAPK1 overexpression changed the physiological characteristics and phenotypes of potato plants under heat stresses. StMAPK1 mediates photosynthesis and maintains membrane integrity of potato plants in response to heat stress. Stress response genes (StP5CS, StCAT, StSOD, and StPOD) in potato plants were altered by StMAPK1 dysregulation. mRNA expression of heat stress genes (StHSP90, StHSP70, StHSP20, and StHSFA3) was affected by StMAPK1.ConclusionsStMAPK1 overexpression increases the heat-tolerant capacity of potato plants at the morphological, physiological, molecular, and genetic levels.

IntroductionThe lack of systematic investigations of arbuscular mycorrhizal fungi (AMF) community composition is an obstacle to AMF biotechnological applications in antimony (Sb)- and arsenic (As)-polluted soil.MethodsMorphological and molecular identification were applied to study the AMF community composition in Sb- and As-contaminated areas, and the main influencing factors of AMF community composition in Sb- and As-contaminated areas were explored.Results(1) A total of 513,546 sequences were obtained, and the majority belonged to Glomeraceae [88.27%, 193 operational taxonomic units (OTUs)], followed by Diversisporaceae, Paraglomeraceae, Acaulosporaceae, Gigasporaceae, and Archaeosporaceae; (2) the affinity between AMF and plants was mainly related to plant species (F = 3.488, p = 0.022 < 0.050), which was not significantly correlated with the total Sb (TSb) and total As (TAs) in soil; (3) the AMF spore density was mainly related to the available nitrogen, available potassium, and total organic carbon; (4) The effect of soil nutrients on AMF community composition (total explanation: 15.36%) was greater than that of soil Sb and As content (total explanation: 5.80%); (5) the effect of TAs on AMF community composition (λ = −0.96) was more drastic than that of TSb (λ = −0.21), and the effect of As on AMF community composition was exacerbated by the interaction between As and phosphorus in the soil; and (6) Diversisporaceae was positively correlated with the TSb and TAs.DiscussionThe potential impact of As on the effective application of mycorrhizal technology should be further considered when applied to the ecological restoration of Sb- and As-contaminated areas.

BackgroundRecent developments in MIBC treatment suggest good efficacy of bladder sparing treatment combined with immune checkpoint inhibitor. However, there is no standard treatment mode. A retrospective analysis was conducted to reveal the efficacy and safety of PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy.MethodsWe retrospectively analyzed 25 patients with MIBC T2-T3N0M0 disease who were unfit or unwilling to undergo RC. These patients underwent the maximum TURBT followed by PD-1 inhibitor (Tislelizumab or Toripalimab) in combination with radiotherapy or chemoradiotherapy (gemcitabine plus cisplatin) between April 2020 and May 2022. The primary outcome was clinical complete response (cCR) rate. The secondary outcomes were disease free survival (DFS) and overall survival (OS).ResultsRevised: Of 25 patients, 22 were T2 (88%), while 3 were T3 (12%). The median age is 65 years (51–80). Twenty-one patients had programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or more, and 4 patients had CPS

BackgroundPatients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated.MethodsSerum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12).ResultsPWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16+ monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16+ monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16+ monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11–q13 might be responsible for elevated levels of inflammation in the peripheral immune system.ConclusionThe study highlights that CD16+ monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.

IntroductionNon-alcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of triglycerides within the liver. However, whether the circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol, remnant-C) are related to the occurrence of NAFLD has not yet been studied. This study aims to assess the association of triglycerides and remnant-C with NAFLD in a Chinese cohort of middle aged and elderly individuals.MethodsAll subjects in the current study are from the 13,876 individuals who recruited in the Shandong cohort of the REACTION study. We included 6,634 participants who had more than one visit during the study period with an average follow-up time of 43.34 months. The association between lipid concentrations and incident NAFLD were evaluated by unadjusted and adjusted Cox proportional hazard models. The potential confounders were adjusted in the models including age, sex, hip circumference (HC), body mass index (BMI), systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), diabetes status and cardiovascular disease (CVD) status.ResultsIn multivariable-adjusted Cox proportional hazard model analyses, triglycerides (hazard ratio[HR], 95% confidence interval [CI]:1.080,1.047-1.113;p1.69 mmol/L, HDL-C

Pregnancy exposure of valproic acid (VPA) is widely adopted as a model of environmental factor induced autism spectrum disorder (ASD). Increase of excitatory/inhibitory synaptic transmission ratio has been proposed as the mechanism of VPA induced ASD. How this happened, particularly at the level of excitatory neuron differentiation in human neural progenitor cells (NPCs) remains largely unclear. Here, we report that VPA exposure remarkably inhibited human NPC proliferation and induced excitatory neuronal differentiation without affecting inhibitory neurons. Following VPA treatment, mitochondrial dysfunction was observed before neuronal differentiation, as showed by ultrastructural changes, respiratory complex activity, mitochondrial membrane potential and oxidation levels. Meanwhile, extracellular acidification assay revealed an elevation of glycolysis by VPA stimulation. Interestingly, inhibiting glycolysis by 2-deoxy-d-glucose-6-phosphate (2-DG) efficiently blocked the excitatory neuronal differentiation of human NPCs induced by VPA. Furthermore, 2-DG treatment significantly compromised the VPA-induced expression of H3ac and H3K9ac, and the VPA-induced binding of H3K9ac on the promoter of Ngn2 and Mash1, two key transcription factors of excitatory neuron fate determination. These data, for the first time, demonstrated that VPA biased excitatory neuron differentiation by glycolysis-mediated histone acetylation of neuron specific transcription factors.

ObjectiveBile acids have underlying protective effects on bones structure. Long-term diabetes also causes skeletal disorders including osteoporosis, Charcot arthropathy and renal osteodystrophy. Nevertheless, few studies have reported whether bile acid is associated with bone metabolism in diabetics. This study aimed to explore the relationship between total bile acid (TBA) and bone mineral density (BMD) among patients with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively included 1,701 T2DM patients who were hospitalized in Taian City Central Hospital (TCCH), Shandong Province, China between January 2017 to December 2019. The participants were classified into the osteopenia (n = 573), osteoporosis (n= 331) and control groups (n= 797) according to BMD in the lumbar spine and femoral. The clinical parameters, including TBA, bilirubin, vitamin D, calcium, phosphorus and alkaline phosphatase were compared between groups. Multiple linear regression was used to analyze the relationship between TBA and BMD in lumbar spine, femoral, trochiter, ward’s triangle region. A logistic regression was conducted to develop a TBA-based diagnostic model for differentiating abnormal bone metabolism from those with normal BMD. We evaluated the performance of model using ROC curves.ResultsThe TBA level was significantly higher in patients with osteoporosis (Median[M]= 3.300 μmol/L, interquartile range [IQR] = 1.725 to 5.250 μmol/L) compared to the osteopenia group (M = 3.200 μmol/L, IQR = 2.100 to 5.400 μmol/L) and control group (M = 2.750 μmol/L, IQR = 1.800 to 4.600 μmol/L) (P

Sertoli cell -only syndrome (SCOS) is a type of testicular pathological failure that causes male infertility and no effective treatment strategy, is available for this condition. Moreover, the molecular mechanism underlying its development remains unknown. We identified DExD/H-Box helicase 58 (DDX58) as a key gene in SCOS based on four datasets of testicular tissue samples obtained from the Gene Expression Synthesis database. DDX58 was significantly upregulated in SCOS testicular Sertoli cells. Moreover, high expression of DDX58 was positively correlated with the expression of several testicular inflammatory factors, such as IL -1β, IL-18, and IL-6. Interestingly, DDX58 could be induced in the D-galactose (D-gal)-stimulated TM4 cell injury model. Whereas silencing of DDX58 inhibited D-gal -mediated p65 expression, inflammatory cytokine release, and growth arrest. Mechanistically, we found that DDX58 acts as an RNA-binding protein, which enhances p65 expression by promoting mRNA stability. Furthermore, p65 gene silencing decreased the expression of inflammatory cytokines and inhibition of cell growth in D-gal-induced cells. In conclusion, our findings demonstrate that DDX58 promotes inflammatory responses and growth arrest in SCOS Sertoli cells by stabilizing p65 mRNA. Accordingly, the DDX58/p65 regulatory axis might be a therapeutic target for SCOS.

Escherichia coli is the main cause of postweaning diarrhea in pigs, leading to economic loss. As a probiotic, Lactobacillus reuteri has been used to inhibit E. coli in clinical applications; however, its integrative interactions with hosts remain unclear, especially in pigs. Here, we found that L. reuteri effectively inhibited E. coli F18ac adhering to porcine IPEC-J2 cells, and explored the genome-wide transcription and chromatin accessibility landscapes of IPEC-J2 cells by RNA-seq and ATAC-seq. The results showed that some key signal transduction pathways, such as PI3K-AKT and MAPK signaling pathways, were enriched in the differentially expressed genes (DEGs) between E. coli F18ac treatment with and without L. reuteri groups. However, we found less overlap between RNA-seq and ATAC-seq datasets; we speculated that this might be caused by histones modification through ChIP-qPCR detection. Furthermore, we identified the regulation of the actin cytoskeleton pathway and a number of candidate genes (ARHGEF12, EGFR, and DIAPH3) that might be associated with the inhibition of E. coli F18ac adherence to IPEC-J2 cells by L. reuteri. In conclusion, we provide a valuable dataset that can be used to seek potential porcine molecular markers of E. coli F18ac pathogenesis and L. reuteri antibacterial activity, and to guide the antibacterial application of L. reuteri.

αvβ3 is overexpressed in various tumor cells and plays a key role in tumor genesis, invasion, and metastasis. Therefore, it is of great significance to precisely detect the αvβ3 level in cells via a simple method. For this purpose, we have constructed a peptide-coated platinum (Pt) cluster. Due to its bright fluorescence, well-defined Pt atom numbers, and peroxidase-like catalytic activity, this cluster can be used to evaluate αvβ3 levels in cells by fluorescence imaging, inductively coupled plasma mass spectrometry (ICP-MS), and catalytic amplification of visual dyes, respectively. In this report, the expression level of αvβ3 in living cells is well-detected by the naked eye under an ordinary light microscope when the Pt cluster binds to αvβ3 in cells and catalyzes non-color 3,3′-diaminobenzidine (DAB) into brown-colored molecules in situ. Moreover, SiHa, HeLa, and 16HBE cell lines with different αvβ3 expression levels can be visually distinguished by the peroxidase-like Pt clusters. This research will provide a reliable method for the simple detection of αvβ3 levels in cells.

IntroductionThe pear pulp is formed by the development of the ovary wall, which is the somatic cell of the female parent, and its genetic traits are identical to those of the female parent, so that its phenotypic traits should also be identical to those of the female parent. However, the pulp quality of most pears, especially the stone cell clusters (SCCs) number and degree of polymerization (DP), were significantly affected by the paternal type. Stone cells are formed by the deposition of lignin in parenchymal cell (PC) walls. Studies on the effect of pollination on lignin deposition and stone cell formation in pear fruit have not been reported. Methods: In this study, 'Dangshan Su' (P. bretschneideri Rehd.) was selected as the mother tree, while 'Yali' (P. bretschneideri Rehd.) and 'Wonhwang' (P. pyrifolia Nakai.) were used as the father trees to perform cross-pollination. We investigated the effects of different parents on SCCs number and DP, and lignin deposition by microscopic and ultramicroscopic observation.Results and DiscussionThe results showed that the formation of SCCs proceeds was consistent in DY and DW, but the SCC number and DP in DY were higher than that in DW. Ultramicroscopy revealed that the lignification process of DY and DW were all from corner to rest regions of the compound middle lamella and the secondary wall, with lignin particles deposited along the cellulose microfibrils. They were alternatively arranged until they filled up the whole cell cavity to culminate in the formation of stone cells. However, the compactness of the wall layer of cell wall was significantly higher in DY than in DW. We also found that the pit of stone cell was predominantly single pit pair, they transported degraded material from the PCs that were beginning to lignify out of the cells. Stone cell formation and lignin deposition in pollinated pear fruit from different parents were consistent, but the DP of SCCs and the compactness of the wall layer were higher in DY than that in DW. Therefore, DY SCC had a higher ability to resist the expansion pressure of PC.

Primary familial brain calcification (PFBC) is a rare neurodegenerative and neuropsychiatric disorder characterized by bilateral symmetric intracranial calcification along the microvessels or inside neuronal cells in the basal ganglia, thalamus, and cerebellum. Slc20a2 homozygous (HO) knockout mice are the most commonly used model to simulate the brain calcification phenotype observed in human patients. However, the cellular and molecular mechanisms related to brain calcification, particularly at the early stage much prior to the emergence of brain calcification, remain largely unknown. In this study, we quantified the central nervous system (CNS)-infiltrating T-cells of different age groups of Slc20a2-HO and matched wild type mice and found CD45+CD3+ T-cells to be significantly increased in the brain parenchyma, even in the pre-calcification stage of 1-month-old -HO mice. The accumulation of the CD3+ T-cells appeared to be associated with the severity of brain calcification. Further immunophenotyping revealed that the two main subtypes that had increased in the brain were CD3+ CD4− CD8– and CD3+ CD4+ T-cells. The expression of endothelial cell (EC) adhesion molecules increased, while that of tight and adherents junction proteins decreased, providing the molecular precondition for T-cell recruitment to ECs and paracellular migration into the brain. The fusion of lymphocytes and EC membranes and transcellular migration of CD3-related gold particles were captured, suggesting enhancement of transcytosis in the brain ECs. Exogenous fluorescent tracers and endogenous IgG and albumin leakage also revealed an impairment of transcellular pathway in the ECs. FTY720 significantly alleviated brain calcification, probably by reducing T-cell infiltration, modulating neuroinflammation and ossification process, and enhancing the autophagy and phagocytosis of CNS-resident immune cells. This study clearly demonstrated CNS-infiltrating T-cells to be associated with the progression of brain calcification. Impairment of blood–brain barrier (BBB) permeability, which was closely related to T-cell invasion into the CNS, could be explained by the BBB alterations of an increase in the paracellular and transcellular pathways of brain ECs. FTY720 was found to be a potential drug to protect patients from PFBC-related lesions in the future.

BackgroundAcute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion.MethodsWe retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated.ResultsAmong the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0–2 (48.8 vs. 52.3%, p = 0.76).ConclusionsRescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.

PurposeChordoma is a rare and locally invasive neoplasm, and the prognostic factors are limited. Deregulation of Histone 3 lysine 27 (H3K27) trimethylation (H3K27me3) is considered to be related with poor prognosis in some tumors. The purpose of this study was to detect the expression of H3K27me3 in chordomas and analyze the correlation with clinicopathological features and explore the roles as potential prognostic markers and therapeutic targets.Material and methodSpecimens of 162 chordoma patients (consisting of 156 conventional chordoma, 4 dedifferentiated chordoma and 2 poorly differentiated chordoma) were enrolled in a tissue microarray (TMA) in order to assess the immunohistochemical staining by H3K27me3 antibodies. Correlations between H3K27me3 expression and clinicopathological features were analyzed. Clinical data of the patients were correlated and survival analysis was performed. Kaplan-Meier survival curves and log-rank test were used to analyze the recurrence-free survival (RFS) and overall survival (OS). Multivariate Cox regression analyses were used to identify potential prognostic factors.ResultsThe expression of H3K27me3 was lower in 37 chordoma patients (37/162, 22.8%), and higher in 125 patients (125/162, 77.2%). H3K27me3-low expression significantly correlated with spine location (P < 0.001), conventional histological subtype (P < 0.001), and recurrence (P < 0.001). Log-rank test showed that H3K27me3-low expression was associated with poor RFS (P =0.027) and OS (P =0.009) in conventional chordoma patients. Cox multivariate analysis revealed that low expression of H3K27me3 was an independent predictor of poor OS (P =0.007) and RFS (P =0.025) in conventional chordoma patients.ConclusionsOur study indicates that low expression of H3K27me3 might be considered as a predictor for poor prognosis and recurrence, and it may provide a potential therapeutic target for conventional chordoma patients.

IntroductionIt is well-documented that systemic lupus erythematosus (SLE) is associated with dementia. However, the genetic causality of this association remains unclear. Mendelian randomization (MR) was used to investigate the potential causal relationship between SLE and dementia risk in the current study.MethodsWe selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from publicly available genome-wide association studies (GWAS). Summary level statistics were obtained from the dementia GWAS database. MR estimates were performed using the inverse variance weighted (IVW) method, MR-Egger method and weighted median (WM) method. Cochran’s Q test, the intercept of MR-Egger, MR-Pleiotropy Residual Sum and Outlier method, leave-one-out analysis and funnel plot were applied for sensitivity analyses.ResultsNo significant causal association was found between SLE and any type of dementia, including Alzheimer’s disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. These findings were robust across several sensitivity analyses.ConclusionOverall, our findings do not support a causal association between SLE and dementia risk.

BackgroundNumerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR).MethodsFourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR–Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses.ResultsIn MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701–1.089, p = 0.230], MR–Egger (OR: 0.944, 95% CI: 0.692–1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678–1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999–1.001, p = 0.683).ConclusionOur findings reveal no significant causal association between circulating ADPN and AD risk.

Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC.Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions.Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs.Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC.

Oxidative stress is caused by an imbalance between prooxidants and antioxidants, which is the cause of various chronic human diseases. Lactic acid bacteria (LAB) have been considered as an effective antioxidant to alleviate oxidative stress in the host. To obtain bacterium resources with good antioxidant properties, in the present study, 113 LAB strains were isolated from 24 spontaneously fermented chili samples and screened by tolerance to hydrogen peroxide (H2O2). Among them, Lactobacillus plantarum GXL94 showed the best antioxidant characteristics and the in vitro antioxidant activities of this strain was evaluated extensively. The results showed that L. plantarum GXL94 can tolerate hydrogen peroxide up to 22 mM, and it could normally grow in MRS with 5 mM H2O2. Its fermentate (fermented supernatant, intact cell and cell-free extract) also had strong reducing capacities and various free radical scavenging capacities. Meanwhile, eight antioxidant-related genes were found to up-regulate with varying degrees under H2O2 challenge. Furthermore, we evaluated the probiotic properties by using in vitro assessment. It was showed that GXL94 could maintain a high survival rate at pH 2.5% or 2% bile salt or 8.0% NaCl, live through simulated gastrointestinal tract (GIT) to colonizing the GIT of host, and also show higher abilities of auto-aggregation and hydrophobicity. Additionally, the usual antibiotic susceptible profile and non-hemolytic activity indicated the safety of the strain. In conclusion, this study demonstrated that L. plantarum GXL94 could be a potential probiotic candidate for producing functional foods with antioxidant properties.

Green economy development has become a mainstream value orientation in social and global economic development to protect and improve the ecological environment. Multiple stakeholders are needed to address complex issues, such as climate change and its impact on the ecological environment and public health. This study investigates the impact of energy policy and green finance on green economic recovery via the controlling role of social capital and public health. An entropy approach was used to measure the green economic index in addition to an econometric approximation for interpreting the longitudinal dataset for the scenarios for E7 countries between 2010 and 2020. The findings show that the development of green finance significantly improves green productivity. Higher levels of economic and social conditions, a lower level of public involvement in environmental protection, and a higher level of pollution amplify this positive effect. On the other hand, energy policy can enhance the impact of green finance development. The findings suggest that the empirical findings benefit green finance planning and energy policy.

Meishan pigs are a famous local pig breed in China, with high fertility and early sexual maturity, and stronger immunity compared to other breeds. The spleen is the largest lymphoid organ in pigs and performs essential functions, such as those relating to immunity and haematopoiesis. The invasion of many pathogenic microorganisms in pigs is associated with spleen damage. Long non-coding RNAs participate in a broad range of biological processes and have been demonstrated to be associated with splenic immune regulation. However, the expression network of mRNAs and lncRNAs in the spleen of Meishan pigs remains unclear. This study collected spleen tissues from Meishan piglets at three different ages as a model, and mRNA and lncRNA transcripts were profiled for each sample. Additionally, 1,806 differential mRNAs and 319 differential lncRNAs were identified. A complicated interaction between mRNAs and lncRNAs was identified via WGCNA, demonstrating that lncRNAs are a crucial regulatory component in mRNA. The results show that the modules black and red have similar mRNA and lncRNA transcription patterns and are mainly involved in the process of the immune defense response. The core genes (DHX58 and IFIT1) and key lncRNAs (TCONS-00002102 and TCONS-00012474) of piglet spleen tissue were screened using the ceRNA network. The expression of these genes is related to the immune response of pigs. Our research may contribute to a further understanding of mRNA and lncRNA expression in the spleen of piglets, and provide new ideas to improve the disease resistance of piglets.

Purpose: To establish an effective prognostic model for patients with clear cell renal cell carcinoma (ccRCC).Methods: We identified four hub differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) database and verified them in the Cancer Gene Atlas (TCGA), STRING, UALCAN, TIMER, and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then used TCGA and International Cancer Genome Consortium (ICGC) to identify tumor pathway molecules highly correlated with hub DEGs. And by further LASSO and Cox regression analysis, we successfully identified five genes as prognostic factors.Results: We successfully identified a risk prediction model consisting of five genes: IGF2BP3, CDKN1A, GSDMB, FABP5, RBMX. We next distributed patients into low-risk and high-risk groups using the median as a cutoff. The low-risk group obviously had better survival than those in the predicted high-risk group. The results showed discrepancies in tumor-associated immune cell infiltration between risk groups. We also combined the risk model with clinical variables to create a nomogram.Conclusion: Our model has a satisfactory predictive effect on the prognosis of ccRCC patients and may provide new ideas for future immune therapy.

The gut microbiota and related metabolites are positively regulated by soluble dietary fiber (SDF). In this study, we explored the effects of SDF from pear pomace (PP) on the regulation of gut microbiota and metabolism in high-fat-diet-fed (HFD-fed) C57BL/6J male mice. The results showed that PP-SDF was able to maintain the HFD disrupted gut microbiota diversity with a significant increase in Lachnospiraceae_UCG-006, Akkermansia, and Bifidobacterium spp. The negative effects of high-fat diet were ameliorated by PP-SDF by regulating lipid metabolisms with a significant increase in metabolites like isobutyryl carnitine and dioscoretine. Correlation analysis revealed that gut microbiota, such as Akkermansia and Lachnospiraceae_UCG-006 in the PP-SDF intervention groups had strong positive correlations with isobutyryl carnitine and dioscoretin. These findings demonstrated that PP-SDF interfered with the host's gut microbiota and related metabolites to reduce the negative effects caused by a high-fat diet.

Mariner-like elements (MLEs) are promising tools for gene cloning, gene expression, and gene tagging. We have characterized two MLE transposons from moso bamboo, Ppmar1 and Ppmar2. Ppmar2, is smaller in size and has higher natural activities, thus making it a more potential genomic tool compared to Ppmar1. Using a two-component system consisting of a transposase expression cassette and a non-autonomous transposon cotransformed in yeast, we investigated the transposition activity of Ppmar2 and created hyperactive transposases. Five out of 19 amino acid mutations in Ppmar2 outperformed the wild-type in terms of catalytic activities, especially with the S347R mutant having 6.7-fold higher transposition activity. Moreover, 36 yeast mutants with single-gene deletion were chosen to screen the effects of the host factors on Ppmar2NA transposition. Compared to the control strain (his3Δ), the mobility of Ppmar2 was greatly increased in 9 mutants and dramatically decreased in 7 mutants. The transposition ability in the efm1Δ mutant was 15-fold higher than in the control, while it was lowered to 1/66 in the rtt10Δ mutant. Transcriptomic analysis exhibited that EFM1 defection led to the significantly impaired DDR2, HSP70 expression and dramatically boosted JEN1 expression, whereas RTT10 defection resulted in significantly suppressed expression of UTP20, RPA190 and RRP5. Protein methylation, chromatin and RNA transcription may affect the Ppmar2NA transposition efficiency in yeast. Overall, the findings provided evidence for transposition regulation and offered an alternative genomic tool for moso bamboo and other plants.

Benthivorous fish disturbance and nitrogen loading are two important factors that influence the community structure of submersed macrophytes, but their interactive effect is not well elucidated. We conducted an outdoor mesocosm experiment to examine the individual and combined effects of these two factors on the growth of two submersed macrophytes of different growth forms, i.e., the rosette-forming Vallisneria natans and the canopy-forming Myriophyllum spicatum. The treatments involved two levels of fish (Carassius auratus) disturbance crossed with two levels (0 and 12 g NH4Cl per month) of ammonium (NH4+-N) loading. For M. spicatum, we found that maximum height (MH) was reduced by 30.7%, 26.4%, and 51.0% in fish addition alone (F) and nitrogen addition treatments (N, F + N), respectively, compared with the control (C) treatment. The density of M. spicatum declined by 20%, 62% and 68.8% in the F, N and F + N treatment. The above-ground biomass (AGB) of M. spicatum respectively reduced by 56.7%, 94%, and 96.5% in the F, N and F + N treatments, and the roots/shoots ratio (R/S) increased by 114%, and 176% in N and N + F treatments, respectively. Regarding V. natans, only the MH in the N treatment was reduced (71.9%), and the density exhibited a reduction of 59.1% and 64.5% in the N and F + N treatments, respectively. The AGB of V. natans was significantly lower in the N (90.3%) and N + F (78.4%) treatments compared with the C treatment, while increased by 60.3% in F treatment. The R/S of V. natans increased by 227%, and 74.4% in the N and F + N treatments compared with the C treatment. The interactive effect of fish disturbance and high N on MH and AGB of V. natans and density of M. spicatum were antagonistic. However, the interactive effect on density and BGB of V. natans and AGB of M. spicatum were negatively synergistic. Moreover, fish activity significantly increased the concentration of total suspended solids (TSS) in the water, while total nitrogen (TN), ammonium, total phosphorus (TP), light, pH and salinity were unaffected. When fish and nitrogen were combined, TN, TP, TSS and salinity increased significantly, while pH decreased. Our study reveals that the interactive effects of fish disturbance and high N are synergistic and/or antagonistic, suggesting that the same stressor interaction may vary from synergistic to antagonistic depending on the response variables and growth forms of the macrophytes examined. Our study contributes to the understanding of how different factors can interact with each other and affect submersed macrophytes in aquatic ecosystems. This is timely and relevant knowledge, considering the range of multiple stressors involved in the decline of aquatic ecosystems worldwide at present.

BackgroundBladder cancer patients have a high recurrence and poor survival rates worldwide. Early diagnosis and intervention are the cornerstones for favorable prognosis. However, commonly used predictive tools cannot meet clinical needs because of their insufficient accuracy.MethodsWe have developed an enhancer RNA (eRNA)-based signature to improve the prediction for bladder cancer prognosis. First, we analyzed differentially expressed eRNAs in gene expression profiles and clinical data for bladder cancer from The Cancer Genome Atlas database. Then, we constructed a risk model for prognosis of bladder cancer patients, and analyzed the correlation between this model and tumor microenvironment (TME). Finally, regulatory network of downstream genes of eRNA in the model was constructed by WGCNA and enrichment analysis, then Real-time quantitative PCR verified the differentiation of related genes between tumor and adjacent tissue.ResultsWe first constructed a risk model composed of eight eRNAs, and found the risk model could be an independent risk factor to predict the prognosis of bladder cancer. Then, the log-rank test and time-dependent ROC curve analysis shown the model has a favorable ability to predict prognosis. The eight risk eRNAs may participate in disease progression by regulating cell adhesion and invasion, and up-regulating immune checkpoints to suppress the immunity in TME. mRNA level change in related genes further validated regulatory roles of eRNAs in bladder cancer. In summary, we constructed an eRNA-based risk model and confirmed that the model could predict the prognosis of bladder cancer patients.

MDM2 and MDM4 proteins are key negative regulators of tumor suppressor p53. MDM2 and MDM4 interact via their RING domains and form a heterodimer polyubiquitin E3 ligase essential for p53 degradation. MDM4 also forms heterodimer E3 ligases with MDM2 isoforms that lack p53-binding domains, which regulate p53 and MDM4 stability. We are working to identify small-molecule inhibitors targeting the RING domain of MDM2-MDM4 (MMRi) that can inactivate the total oncogenic activity of MDM2-MDM4 heterodimers. Here, we describe the identification and characterization of MMRi62 as an MDM4-degrader and apoptosis inducer in leukemia cells. Biochemically, in our experiments, MMRi62 bound to preformed RING domain heterodimers altered the substrate preference toward MDM4 ubiquitination and promoted MDM2-dependent MDM4 degradation in cells. This MDM4-degrader activity of MMRi62 was found to be associated with potent apoptosis induction in leukemia cells. Interestingly, MMRi62 effectively induced apoptosis in p53 mutant, multidrug-resistant leukemia cells and patient samples in addition to p53 wild-type cells. In contrast, MMRi67 as a RING heterodimer disruptor and an enzymatic inhibitor of the MDM2-MDM4 E3 complex lacked MDM4-degrader activity and failed to induce apoptosis in these cells. In summary, this study identifies MMRi62 as a novel MDM2-MDM4-targeting agent and suggests that small molecules capable of promoting MDM4 degradation may be a viable new approach to killing leukemia cells bearing non-functional p53 by apoptosis.

In order to cope with global climate change, an electric vehicle (EV) and new energy building are constantly being innovated and improved. With the popularity and application of big data and Internet of Things, the new energy building with available charging piles may also become a charging station, which can solve the problem of difficult charging of EVs and promote the local energy consumption of the building. Therefore, this study proposes a shared charging concept for buildings, that is, shared photovoltaic, charging, and energy storage building (sPCEB). First, based on the analysis results of big data in cities or settlements of people, a locating method of the sPCEB system is introduced, and further proposes an optimal operating strategy that maximizes the combined benefit of the building. The efficiency and effectiveness of the proposed methods are verified by simulation.

Root rot has been a major problem for cultivated populations of Coptis chinensis var. chinensis in recent years. C. chinensis var. brevisepala, the closest wild relative of C. chinensis var. chinensis, has a scattered distribution across southwestern China and is an important wild resource. Genetic diversity is associated with greater evolutionary potential and resilience of species or populations and is important for the breeding and conservation of species. Here, we conducted multiplexed massively parallel sequencing of the plastomes of 227 accessions of wild and cultivated C. chinensis using 111 marker pairs to study patterns of genetic diversity, population structure, and phylogeography among wild and cultivated C. chinensis populations. Wild and cultivated resources diverged approximately 2.83 Mya. The cultivated resources experienced a severe genetic bottleneck and possess highly mixed germplasm. However, high genetic diversity has been retained in the wild resources, and subpopulations in different locations differed in genotype composition. The significant divergence in the genetic diversity of wild and cultivated resources indicates that they require different conservation strategies. Wild resources require in situ conservation strategies aiming to expand population sizes while maintaining levels of genetic diversity; by contrast, germplasm resource nurseries with genotypes of cultivated resources and planned distribution measures are needed for the conservation of cultivated resources to prevent cultivated populations from undergoing severe genetic bottlenecks. The results of this study provide comprehensive insights into the genetic diversity, population structure, and phylogeography of C. chinensis and will facilitate future breeding and conservation efforts.

Ammonium (NH4-N) produces a paradoxical effect on submersed macrophytes because it is not only the preferred nitrogen source for the growth of plants but also threatens the growth of plants at high concentration. Whether short-term and small-scale physiological toxicity experiments at an individual level can reflect the effects of high ammonium on populations of submersed macrophytes in natural conditions is still unclear. In this study, an 18-month experiment was conducted in six 600 m2 ponds subjected to different levels of ammonium loading. The effects of high ammonium on populations of canopy-forming Myriophyllum spicatum and rosette-forming Vallisneria natans were explored. The results showed that M. spicatum and V. natans populations can develop high cover and height at high ammonium concentration (7 mg/L) at short-term exposures, and V. natans may be tolerant to 18 mg/L ammonium concentration. However, the cover of M. spicatum and the height of both species were inhibited at 2.4 mg/L at long-term exposures. The height of M. spicatum was two to six times higher than that of V. natans across all treatments and control by the end of the experiment, and the cover of M. spicatum was 7–11 times higher than that of V. natans in most NH4-N loading treatments, except the cover of M. spicatum in the highest NH4-N loading treatment with 18 mg/L NH4-N. The rosette-forming V. natans resists ammonium stress by slow growth (shoot elongation) to reduce consumption, while canopy-forming species resist ammonium stress by shoot elongation and canopy development to capture light. Although increasing ammonium concentration may induce severe stress on M. spicatum, the morphological characteristics of this species may, to some extent, release the plants from this stress. Our present study indicates that the negative effects of ammonium stress on the development of populations increased with exposure duration, and the submersed macrophyte community with stronger ability for light capture and dispersal may resist high ammonium stress. Nevertheless, in strongly ammonium-enriched systems, competition and succession cannot be neglected.

BackgroundType I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis.ObjectiveThis study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia.MethodsWe conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium.ResultsProband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 ± 9.46% (p