On-demand bactericidal and self-adaptive antifouling hydrogels for self-healing and lubricant coatings of catheters.

Catheter-related infections are one of the most common nosocomial infections with increasing morbidity and mortality, and robust antibacterial or antifouling catheter coatings remain great challenges for long-term implantation. Herein, multifunctional hydrogel coatings were developed to provide persistent and self-adaptive antifouling and antibacterial effects with self-healing and lubricant capabilities. Polyvinyl alcohol (PVA) with ß-cyclodextrin (ß-CD) grafts (PVA-Cd) and 4-arm polyethylene glycol (PEG) with adamantane and quaternary ammonium compound (QAC) terminals (QA-PEG-Ad) were crosslinked through host-guest recognitions between adamantane and ß-CD moieties to acquire PVEQ coatings. In response to bacterial infections, QACs exhibit reversible transformation between zwitterions (pH 7.4) and cationic lactones (pH 5.5) to generate on-demand bactericidal effect. Highly hydrophilic PEG/PVA backbones and zwitterionic QACs build a lubricate surface and decrease the friction coefficient 10 times compared with that of bare catheters. The antifouling hydrated layer significantly inhibits blood protein adsorption and platelet activation and reveals negligible hemolysis and cytotoxicity. The dynamic host-guest crosslinking achieves full self-healing of cracks in PVEQ hydrogels, and the mechanical profiles were recovered to over 90 % after rejuvenating the broken hydrogels, exhibiting a long-term stability after mechanical stretching, twisting, knotting and compression. After subcutaneous implantation and local bacterial infection, the retrieved PVEQ-coated catheters display no tissue adhesion and 3 log folds lower bacterial number than that of bare catheters. PVEQ coatings effectively prevent the repeated bacterial infections and there are few inflammatory reactions in the surrounding tissue, while substantial lymphoid infiltration and inflammatory cell aggregation occur in muscle tissues around the bare catheter. Thus, this study demonstrates a catheter coating strategy by on-demand bactericidal, self-adaptive antifouling, self-healing and lubricant hydrogels to address medical devices-related infections. STATEMENT OF SIGNIFICANCE: It is estimated over two billion peripheral intravenous catheters are annually used in hospitals around the world, and catheter-associated infection has become a great clinical challenge with rapidly rising morbidity and mortality. Surface coating is considered a promising approach, but substantial challenges remain in the development of coatings that simultaneously satisfy both anti-fouling and antibacterial attributes. Even more, few attempts have been made to design mechanically robust coatings and reversible antibacterial or antifouling capabilities, which are critical for long-term medical implants. To address these challenges, we propose a concise strategy to develop hydrogel coatings from commercially available poly(ethylene glycol) and polyvinyl alcohol. In addition to self-healing and lubricant capabilities, the reversible conversion between zwitterionic and cationic lactones of quaternary ammonium compounds enables on-demand bactericidal and self-adaptive antifouling effects.

Case report: safety and efficacy of lidocaine infusion for the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients.

Introduction: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients. Case series presentation: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported. Conclusion: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.

Shrub encroachment leads to accumulation of C, N, and P in grassland soils and alters C:N:P stoichiometry: A meta-analysis.

Soil stoichiometry of carbon (C), nitrogen (N), and phosphorus (P) are indicators for nutrient balance. Shrub encroachment into grasslands could change nutrient concentrations and stoichiometry in soils, but the general patterns remain unclear. With a meta-analysis of a global dataset covering 344 observations from 68 studies, we examined the responses of grassland soil C:N:P stoichiometry to shrub encroachment under various environmental conditions. Our results show that: 1) Shrub encroachment significantly increased the concentrations of soil C (+29 %), N (+25 %), P (+20 %), C:N (+5 %), C:P (+12 %), and N:P (+6 %). The magnitude of such effects varied with climate, soil texture, and soil layer. 2) Increases in SOC and TN concentrations mainly occurred in Mediterranean and very humid climate zones. Soil C:P and N:P decreased in semi-humid climate zone after shrub encroachment. 3) The increases in SOC and TN concentrations and in the C:N, C:P, and N:P ratios after shrub encroachment were greater in the topsoil than in deeper soil layers. 4) Both finest-textured soil (clay) and coarsest-textured soil (sand) are beneficial for increase of soil nutrient concentrations following shrub encroachment. 5) The magnitude of the change in soil C:N was negatively correlated with the duration of shrub encroachment, due to greater increases in soil TN than in SOC concentrations with longer durations of encroachment. Our results indicate that soil stoichiometric shifts in shrub-encroached grasslands are relatively sensitive to environmental factors, including soil texture, soil pH, and climate. These findings help us to better understand the effects of shrub encroachment on biogeochemical cycling, functioning, and services in grasslands across a broad range of spatio-temporal scales.

Decomposition of air conditioning electricity consumption based on effective duration.

As the share of air conditioning electricity consumption within total grid electricity consumption grows, the decomposition of such consumption becomes increasingly crucial for assessing electricity usage patterns, devising consumption scheduling strategies, and maintaining the stability of the power grid. Although there is a strong correlation between apparent temperature and air conditioning electricity consumption, the literature currently available seldom explores the impact of apparent temperature on this consumption. Moreover, there is a scarcity of effective assessment indices to evaluate the efficacy of air conditioning electricity consumption breakdown. This study introduces a method for decomposing electricity consumption from air conditioning units, utilizing effective duration as a basis to tackle these issues. By employing an apparent temperature model as a constraint, this approach identifies the effective operating time of air conditioning and constructs a constrained convex optimization problem to estimate air conditioning power usage. Additionally, a novel evaluation index for the effectiveness of air conditioning electricity consumption decomposition is proposed, which includes penalties for negative decomposed consumption, alongside the traditional consistency index. Comparative experiments are conducted using real electricity consumption data from Fujian Province. Empirical results indicate that the methodology for air conditioning electricity consumption decomposition presented in this paper aligns more closely with actual conditions. Furthermore, the evaluation metrics introduced for the decomposition of air conditioning electricity consumption are adept at precisely gauging the quality of the air conditioning electricity consumption data.

Genome-wide identified VvOFP genes family and VvOFP4 functional characterization provide insight into fruit shape in grape.

Ovate Family Proteins (OFPs) are emerging as novel transcriptional regulators of fruit shape. Despite their established role in various species, their involvement in regulating grape fruit shape remains understudied. This study encompassed a comprehensive evaluation of 16 grape OFP genes in total at the whole genome level. Phylogenetic and synteny analyses established a close relationship between grape VvOFP genes and their tomato counterparts. Expression profiling post-treatment with gibberellic acid (GA3) and thidiazuron (TDZ) revealed that certain OFP genes responded to these regulators, with VvOFP4 showing peak expression three days post-anthesis. Functional assays via overexpression of VvOFP4 in tobacco and tomato altered the morphology of both vegetative and reproductive organs, including leaves, stamens, and fruits/pods. Paraffin sections of transgenic tobacco stems and tomato fruits demonstrated that VvOFP4 overexpression modifies cell dimensions, leading to changes in organ morphology. Additionally, treatments with GA3 and TDZ similarly influenced the shape of grape pulp cells and thereby the overall fruit morphology. These findings suggest that the VvOFP4 gene plays a crucial role in fruit shape determination by modulating cell shape and presents a potential target for future grape breeding programs aimed at diversifying fruit shapes.

Species Composition of a Small Mammal Community and Prevalence of Echinococcus spp. in the Alpine Pastoral Area of the Eastern Tibetan Plateau.

We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014-2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools.

Relief effect of biochar on continuous cropping of tobacco through the reduction of p-hydroxybenzoic acid in soil.

Biochar application to soil has proven to be an excellent approach for decreasing the concentration of auto-toxic compounds and promoting plant growth in continuous-cropping fields. However, the mechanisms underlying the action pathway among biochars, auto-toxic compounds and tobacco remain unknown. In this study, we conducted an experiment tracking the incidence rate of black rot and auto-toxic compounds for a 3-year continuous-cropping tobacco pot trial in response to biochar treatment intensity compared with that of non-biochar treatment. Biochar inhibited the incidence of black rot. Using ultra-high-performance liquid chromatography-mass spectrometry (UPLC‒MS/MS), we revealed that biochar can effectively decrease the concentration of p-hydroxybenzoic acid (PHA), which is associated with the incidence rate of black rot (R2 = 0.890, p < 0.05). The sorption kinetics and isotherm of PHA sorption on biochar indicate that the coexistence of heterogeneous and monolayer sorption plays an important role in the adsorption process. Using Molecular dynamics (MD), Density functional theory (DFT) and Independent gradient model (IGM) analyses, we provide evidence that van der Waals force (vdW), π-π bonds and H-bonds between biochar and PHAs are the dominant factors that affect adsorption capacity. Moreover, the molecular adsorption rate (Nbiochar: NPHAs = 1:4) was theoretically calculated. In contrast, biochar dramatically increased nutrient retention capacity and improved soil properties, further enhancing tobacco quality, including its agronomic and physiological traits. Therefore, we considered that biochar not only relieved continuous cropping but also improved soil properties suitable for tobacco growth. Together, we demonstrate that the action of biochar in continuously cropped soil improves soil traits and alleviates auto-toxic compound toxicity. These data contribute to the direction of modified biochar application to improve continuous-cropping soil.

QingChang-XiaoPi decoction ameliorates intestinal inflammation of ulcerative colitis by regulating the pathogenicity of Th17 cells.

BACKGROUND: QingChang-XiaoPi Decoction (QCXPY), a Chinese herbal prescription, has been employed in the treatment of ulcerative colitis (UC) in China. However, its molecular mechanism of action in UC remains unclear. PURPOSE: To elucidate the therapeutic effects of QCXPY against UC and reveal its mechanism of action. STUDY DESIGN: We conducted a single-arm observation to evaluate the clinical efficacy of QCXPY in patients with mild-to-moderate UC. Inclusion and exclusion criteria were established to ensure the eligibility of participants, with a focus on excluding patients with specific conditions or complications that could confound the results. METHODS: The expression of inflammatory factors in patients' serum was detected using a Luminex assay. The main components of QCXPY were identified using UHPLC-Q-TOF-MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. The efficacy of QCXPY was evaluated using a dextran sulfate sodium (DSS)-induced mouse model. Disease activity index (DAI), histopathological score, cytokine detection by ELISA, T-helper 17 (Th17) cell proportion by flow cytometry, expression of the IL-23/IL-17 axis, and changes in the levels of its downstream effectors were detected by immunohistochemistry, immunofluorescence, and western blotting. RESULTS: QCXPY could alleviate the symptoms of diarrhea, abdominal pain, abdominal distension, and purulent stool in patients with mild-to-moderate UC. Moreover, it reduced the expression of IL-6, IL-17, and IL-23 in serum; alleviated DSS-induced experimental colitis in mice; reduced DAI, pathological scores, and the expressions of IL-6, IL-17, and IL-23 in colon tissue; and decreased the proportion of pathogenic Th17 cells and the expression of STAT3 and phospho-STAT3. CONCLUSION: This study confirmed for the first time that QCXPY could alleviate intestinal symptoms, reduce the levels of serum inflammatory factors, and improve the quality of life of patients with mild-to-moderate UC. Its mechanism of action may involve reducing the secretion of inflammatory cytokines, moderating the pathogenicity of Th17 cells, and inhibiting STAT3 phosphorylation, thereby alleviating intestinal inflammation in UC.

Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy.

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

Promoter replication of grape MYB transcription factor is associated with a new red flesh phenotype.

KEY MESSAGE: In our study, we discovered a fragment duplication autoregulation mechanism in 'ZS-HY', which may be the reason for the phenotype of red foliage and red flesh in grapes. In grapes, MYBA1 and MYBA2 are the main genetic factors responsible for skin coloration which are located at the color loci on chromosome 2, but the exact genes responsible for color have not been identified in the flesh. We used a new teinturier grape germplasm 'ZhongShan-HongYu' (ZS-HY) which accumulate anthocyanin both in skin and flesh as experimental materials. All tissues of 'ZS-HY' contained cyanidin 3-O-(6″-p-coumaroyl glucoside), and pelargonidins were detected in skin, flesh, and tendril. Through gene expression analysis at different stage of flesh, significant differences in the expression levels of VvMYBA1 were found. Gene amplification analysis showed that the VvMYBA1 promoter is composed of two alleles, VvMYBA1a and 'VvMYBA1c-like'. An insertion of a 408 bp repetitive fragment was detected in the allele 'VvMYBA1c-like'. In this process, we found the 408 bp repetitive fragment was co-segregated with red flesh and foliage phenotype. Our results revealed that the 408 bp fragment replication insertion in promoter of 'VvMYBA1c-like' was the target of its protein, and the number of repeat fragments was related to the increase of trans-activation of VvMYBA1 protein. The activation of promoter by VvMYBA1 was enhanced by the addition of VvMYC1. In addition, VvMYBA1 interacted with VvMYC1 to promote the expression of VvGT1 and VvGST4 genes in 'ZS-HY'. The discovery of this mutation event provides new insights into the regulation of VvMYBA1 on anthocyanin accumulation in red-fleshed grape, which is of great significance for molecular breeding of red-fleshed table grapes.

Association of anti-Müllerian hormone and insulin resistance in adolescent girls with polycystic ovary syndrome.

INTRODUCTION: Insulin resistance (IR) is confirmed as an important feature among polycystic ovary syndrome (PCOS) patients. Anti-Müllerian hormone (AMH), a vital marker of ovarian dysfunction, is proposed for inclusion in the diagnosis of PCOS in adolescents. We sought to investigate the relationship between the AMH level and IR in Chinese girls with PCOS. MATERIAL AND METHODS: 92 girls with PCOS aged 14-18 years were enrolled and divided into 2 subgroups: PCOS with IR group (n = 25) and PCOS without IR group (n = 67). A homeostasis model assessment-insulin resistance (HOMA-IR) value ≥ 2.5 was defined as IR. Clinical data and biochemical indexes were compared between the 2 groups. Multivariate logistic regression analysis and multivariate linear regression analysis were performed to determine which clinical variables were independently associated with IR and AMH level, respectively. RESULTS: PCOS girls with IR had higher levels of AMH than those of PCOS girls without IR (p < 0.01). Moreover, body mass index, triglyceride, and AMH values were shown to be independent risk factors for HOMA-IR after multivariate analysis. Meanwhile, age, insulin, and follicle-stimulating hormone levels were significantly related to AMH levels in those girls. CONCLUSIONS: Our findings show that AMH is an independent determinant of IR in PCOS adolescents, and the fasting insulin level is closely associated with the AMH level, which indicates that the AMH pathway might play a role in the development of IR in PCOS adolescents. The interaction between AMH and IR in PCOS girls warrants further large-scale evaluation.

Adjustable ultraviolet and white light dual emission phosphor Y2Sr(Ga1-yAly)4SiO12:xPr3+ for health lighting.

Mid-ultraviolet light (290-320 nm) can promote human vitamin D synthesis, which helps in the prevention and treatment of rickets and cartilage disease. For people who lack sufficient ultraviolet radiation all year round, it is significant to supplement the ultraviolet component in daily lighting sources. However, there are few luminous materials showing a combination of mid-ultraviolet light and white light emission on the market. Here, we designed a new material, Y2Sr(Ga1-yAly)4SiO12:xPr3+ (YSGAS:xPr3+), which achieves dual emission of 320 nm ultraviolet and white light from a single substrate with a single doped phosphor. Without Al3+ ions, the emission intensity of the Y2SrGa4SiO12:xPr3+ phosphor shows a contribution-dependent relationship, and concentration quenching due to exchange interaction. The crystal field environment was regulated by partially replacing Ga3+ ions with Al3+ ions. After introducing Al3+, YSGAS:xPr3+ phosphors exhibit dual ultraviolet emission (320 nm) and visible light emission. The emission color of YSGAS:xPr3+ can be adjusted by changing the Al3+ concentration, and Y2Sr(Ga0.6Al0.4)4SiO12:1%Pr3+ emits both ultraviolet light and white light. The LED device prepared by using the YSGAS:Pr3+ phosphor and chips shows a color temperature of 4858 K and appropriate CIE coordinates of (0.3474, 0.3390), indicating wide application prospects in the field of "health lighting" for particular populations.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.

Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D. IMPORTANCE: Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.

Integrated Transcriptomic and Proteomic Analysis Identifies Novel Regulatory Genes Associated with Plant Growth Regulator-Induced Astringency in Grape Berries.

Astringency influences the sensory characteristics and flavor quality of table grapes. We tested the astringency sensory attributes of berries and investigated the concentration of flavan-3-ols/proanthocyanidins (PAs) in skins after the application of the plant growth regulators CPPU and GA3 to the flowers and young berries of the "Summer Black" grape. Our results showed that CPPU and GA3 applications increase sensory astringency perception scores and flavan-3-ol/proanthocyanidin concentrations. Using integrated transcriptomic and proteomic analysis, differentially expressed transcripts and proteins associated with growth regulator treatment were identified, including those for flavonoid biosynthesis that contribute to the changes in sensory astringency levels. Transient overexpression of candidate astringency-related regulatory genes in grape leaves revealed that VvWRKY71, in combination with VvMYBPA1 and VvMYC1, could promote the biosynthesis of proanthocyanidins, while overexpression of VvNAC83 reduced the accumulation of proanthocyanidins. However, in transient promoter studies in Nicotiana benthamiana, VvWRKY71 repressed the promoter of VvMYBPA2, while VvNAC83 had no significant effect on the promoter activity of four PA-related genes, and VvMYBPA1 was shown to activate its own promoter. This study provides new insights into the molecular mechanisms of sensory astringency formation induced by plant growth regulators in grape berries.

Biomarkers prediction and immune landscape in ulcerative colitis: Findings based on bioinformatics and machine learning.

BACKGROUND: Ulcerative colitis (UC) presents diagnostic and therapeutic difficulties. The primary objective of this study is to identify efficacious biomarkers for diagnosis and treatment, as well as acquire a deeper understanding of the immuneological characteristics associated with the disease. METHODS: Datasets relating to UC were obtained from GEO database. Among these, three datasets were merged to create a metadata for bioinformatics analysis and machine learning. Additionally, one dataset specifically utilized for external validation. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) were employed to screen signature genes. The artificial neural network (ANN) model and receiver operating characteristic (ROC) curve were used to assess the diagnostic performance of signature genes. The single sample gene set enrichment analysis (ssGSEA) was applied to reveal the immune landscape. Finally, the relationship between the signature genes, immune infiltration, and clinical characteristics was investigated through correlation analysis. RESULT: By intersecting the result of LASSO, RF and WGCNA, 8 signature genes were identified, including S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14. The biological progress of this gene mostly encompasses acute inflammatory response, aggregation and chemotaxis of leukocyte, and response to lipopolysaccharide by mediating IL-17 signaling pathway, NF-kappa B signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway. Immune infiltration analysis shows 25 immune cells are significantly elevated in UC samples. Moreover, these signature genes exhibit a strong correlation with various immune cells and a mild to moderate correlation with the Mayo score. CONCLUSION: S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14 have been identified as credible potential biomarkers for the diagnosis and therapy of UC. The immune response mediated by these signature biomarkers plays a crucial role in the occurrence and advancement of UC by means of the reciprocal interaction between the signature biomarkers and immune-infiltrated cells.

Excitatory neurons in the lateral parabrachial nucleus mediate the interruptive effect of inflammatory pain on a sustained attention task.

BACKGROUND: Attentional deficits are among the most common pain-induced cognitive disorders. Pain disrupts attention and may excessively occupy attentional resources in pathological states, leading to daily function impairment and increased disability. However, the neural circuit mechanisms by which pain disrupts attention are incompletely understood. METHODS: We used a three-choice serial reaction time task (3CSRTT) to construct a sustained-attention task model in male C57BL/6J mice. Formalin or complete Freund's adjuvant was injected into a paw to establish an inflammatory pain model. We measured changes in 3CSRTT performance in the two inflammatory pain models, and investigated the neural circuit mechanisms of pain-induced attentional deficits. RESULTS: Acute inflammatory pain impaired 3CSRTT performance, while chronic inflammatory pain had no effect. Either inhibition of the ascending pain pathway by blockade of the conduction of nociceptive signals in the sciatic nerve using the local anesthetic lidocaine or chemogenetic inhibition of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) neurons in the lateral parabrachial nucleus (LPBN) attenuated the acute inflammatory pain-induced impairment of 3CSRTT performance, while chemogenetic activation of CaMKIIα neurons in the LPBN disrupted the 3CSRTT. Furthermore, the activity of CaMKIIα neurons in the LPBN was significantly lower on Day 2 after complete Freund's adjuvant injection than on the day of injection, which correlated with the recovery of 3CSRTT performance during chronic inflammatory pain. CONCLUSIONS: Activation of excitatory neurons in the LPBN is a mechanism by which acute inflammatory pain disrupts sustained attention. This finding has implications for the treatment of pain and its cognitive comorbidities.

Speed behaviour and mental workload of small-spacing expressway interchanges based on field driving test.

Many small-spacing interchanges (SSI) appear with the improvement of the expressway network. To investigate the speed and mental workload characteristics in the SSI and acquire the mechanism of the influence of speed on the drivers' workload, 37 participants were recruited to perform a field driving test. Each driver performed four driving conditions (i.e. ramp-mainline, mainline-ramp, mainline driving, and auxiliary lane driving). The speed and drivers' electrocardiogram (ECG) data were collected using SpeedBox speed acquisition equipment and PhysioLAB physiological instrument. The heart rate increase (HRI) index was used to analyse the drivers' mental workload regularity. The relationship model between speed and HRI was developed to examine the impact of speed on HRI. The results show that the speed variation in the SSI displayed two patterns: 'decrease - increase and continuous decrease.' The drivers' HRI variation presented four patterns: 'convex curve, continuously increasing, continuously decreasing and concave curve'. SSI's influenced area length is given based on the speed and HRI variation regularity. HRI is significantly higher when driving in the ramp-mainline condition in the SSI than when driving in other conditions, indicating that drivers are more nervous when merging with the mainline traffic. HRI increases significantly in the first 50% of the weaving area in four driving conditions, indicating that vehicle weaving greatly influences the drivers' mental workload. A positive correlation exists between vehicle speed and drivers' HRI without interference from other vehicles and road alignment.

The shorter spacing of the interchange will result in a more difficult driving task for the drivers. This study shows that drivers have the highest mental workload in ramp-mainline driving condition at small-spacing interchanges. The first half of the weaving area is the area where drivers' mental workload increases significantly, and is a high-risk section for small-spacing interchanges. This study can provide a reference for the revision of the allowable minimum interchange spacing in the corresponding specification, and the calibration of the simulation test parameters for similar scenarios.