Development and application of a comprehensive evaluation index system for groundwater quality evolution patterns.

In recent years, driven by rapid socio-economic development and intensified human activities, the groundwater quality has exhibited a concerning trend of degradation. The challenge lies in integrating the impacts of both natural and anthropogenic factors to establish a scientific evaluation framework for the evolution of groundwater quality. This study adopts the model of driving forces - pressures - state - impacts - responses (DPSIR) proposed by the European Environment Agency, in conjunction with the Analytic Hierarchy Process (AHP) and Information Entropy Theory (IET), and the Water Quality Index (WQI) evaluation methods, to construct an evaluation index system for groundwater quality evolution that encompasses driving forces, state, and response systems. Initially, twelve indicators relevant to groundwater quality are quantified by screening across three systems, and a functional relationship between the categorization and scoring of each indicator is established. Subsequently, the weights for each system and indicator are obtained through the AHP, and the objective weights of the indicators are determined using the IET. The scores of each indicator are then comprehensively calculated. Finally, based on the defined types of groundwater quality evolution patterns, an integrated assessment of the evolution of groundwater quality over various time periods is conducted. Taking the Shijiazhuang region as a case study and analyzing the hydrochemical data of groundwater from 1985 to 2015, the results indicate a shift in the groundwater quality evolution pattern from one dominated by natural factors to one primarily influenced by human activities (The comprehensive score of the evaluation index system has increased from 1.84 to 3.25). Among these, the application of fertilizers emerges as the most important driving factors affecting groundwater quality. Particularly, nitrate and total hardness (TH) have emerged as the most salient indicators of quality degradation, with a significant escalation in their composite scores. At the outset, nitrate registered a score of 0.408, while TH scored 0.326; yet, these values have sharply ascended to 0.716 and 0.467, respectively, by the advanced stage. The study concludes with a discussion on the accuracy, strengths, limitations, and applicability of the evaluation index system. The establishment of this evaluation framework provides a scientific basis for the management and protection of groundwater resources and serves as a reference for identifying groundwater quality evolution patterns in other regions.

Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation.

OBJECTIVE: Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA. METHODS: The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination. RESULTS: CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27-altered patients was 14.37 (95% CI 2.84-25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940-4.642, p = 0.070). Following dissemination, H3 K27-altered patients had a median postdissemination survival of 8.83 (95% CI 7.13-10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98-34.26) months in those with H3 K27 wildtype (p = 0.008). CONCLUSIONS: Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

Cost-effectiveness of first-line enfortumab vedotin in addition to pembrolizumab for metastatic urothelial carcinoma in the United States.

Background and objective: The EV-302 trial found that the combination of enfortumab vedotin (EV) with pembrolizumab significantly improved survival for patients with metastatic urothelial carcinoma (mUC). However, given the high cost of the drugs, there is a need to assess its value by considering both efficacy and cost. This study assessed the cost-effectiveness of EV plus pembrolizumab as a first-line treatment for patients with mUC from the perspective of U.S. payers. Methods: A Markov model was developed to compare the lifetime costs and effectiveness of EV in combination with pembrolizumab with chemotherapy in the treatment of mUC patients from U.S. payer perspective. Life-years (LYs), quality-adjusted LYs (QALYs), and lifetime costs were estimated. One-way, two-way and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Additionally, subgroup analyses were performed. Results: Compared to chemotherapy, the combination of EV and pembrolizumab provided an additional 2.10 LYs and 1.72 QALYs, at an incremental cost of $962,240.8 per patient. The incremental cost-effectiveness ratio (ICER) is $558,973 per QALY. Subgroup analysis indicated that patients ineligible for cisplatin treatment had a lower ICER compared to those who were eligible for cisplatin. Conclusions: From the perspective of US payers, at a willingness-to-pay threshold of $150,000 per QALY, the combination of EV and pembrolizumab is estimated to not be cost-effective compared to traditional chemotherapy in the first-line treatment of mUC patients.

Trajectory of associative memory impairment during electroconvulsive therapy in depression.

Memory impairment is a serious cognitive side effect of electroconvulsive therapy (ECT) in the treatment of major depressive episodes (MDEs) and has garnered widespread attention in clinical practice, but its underlying evolution pattern during the course of ECT remains rarely understood in detail. Associative memory (AM) is a core indicator that reflects memory impairment in ECT. This study aimed to identify the dynamic trajectory of AM impairment and explore associated predictive factors. 405 intensive longitudinal AM data from 81 patients with MDE were collected at the baseline, after the first, third, fifth, and eighth ECT using five sets of face-cued word memory paradigms. Changes in AM score over time were analyzed using a linear mixed effects model. Trajectory subgroups and predictive factors were investigated using growth mixture model and logistic regression. AM score during ECT were significantly lower than at baseline, with the lowest scores observed after the eighth ECT session. Two trajectories of rapid (N = 56, 69.14%) and slow (N = 25, 30.86%) AM impairment were differentiated. Older female with lower education level were significant predictors contributing to more rapid memory impairment for ECT. The evolving pattern of associative memory impairment during ECT appears to occur early and worsen with subsequent treatment. This study may provide the important evidence understanding of the number effect of ECT sessions on memory impairment and suggest individual factors for predicting ECT memory outcome.

Dynamics of epitranscriptomes uncover translational reprogramming directed by ac4C in rice during pathogen infection.

Messenger RNA modifications play pivotal roles in RNA biology, but comprehensive landscape changes of epitranscriptomes remain largely unknown in plant immune response. Here we report translational reprogramming directed by ac4C mRNA modification upon pathogen challenge. We first investigate the dynamics of translatomes and epitranscriptomes and uncover that the change in ac4C at single-base resolution promotes translational reprogramming upon Magnaporthe oryzae infection. Then by characterizing the specific distributions of m1A, 2'O-Nm, ac4C, m5C, m6A and m7G, we find that ac4Cs, unlike other modifications, are enriched at the 3rd position of codons, which stabilizes the Watson-Crick base pairing. Importantly, we demonstrate that upon pathogen infection, the increased expression of the ac4C writer OsNAT10/OsACYR (N-ACETYLTRANSFERASE FOR CYTIDINE IN RNA) promotes translation to facilitate rapid activation of immune responses, including the enhancement of jasmonic acid biosynthesis. Our study provides an atlas of mRNA modifications and insights into ac4C function in plant immunity.

Sex difference and socioeconomic inequity in hypertension: a national survey study of 98,658 adults from 162 study sites.

BACKGROUND: Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences of hypertension remains unclear. OBJECTIVE: We aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. METHODS: A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs. men) and BP characteristics stratified by individual or combined SES indicators. RESULTS: Systolic and diastolic BP levels and prevalence of hypertension were higher in men than women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared with men. For combined SES, a 9% (prevalence ratio (PR)=0.91, 95% confidence interval (CI)=0.83, 0.98) and a 30% lower probability (PR=0.70, 95% CI=0.63, 0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively compare with low SES while no significant reduction was found in men. CONCLUSIONS: There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

LOX-mediated ECM mechanical stress induces Piezo1 activation in hypoxic-ischemic brain damage and identification of novel inhibitor of LOX.

Hypoxic-ischemic encephalopathy (HIE) poses a significant challenge in neonatal medicine, often resulting in profound and lasting neurological deficits. Current therapeutic strategies for hypoxia-ischemia brain damage (HIBD) remain limited. Ferroptosis has been reported to play a crucial role in HIE and serves as a potential therapeutic target. However, the mechanisms underlying ferroptosis in HIBD remain largely unclear. In this study, we found that elevated lysyl oxidase (LOX) expression correlates closely with the severity of HIE, suggesting LOX as a potential biomarker for HIE. LOX expression levels and enzymatic activity were significantly increased in HI-induced neuronal models both in vitro and in vivo. Notably, we discovered that HI-induced brain tissue injury results in increased stiffness and observed a selective upregulation of the mechanosensitive ion channel Piezo1 in both brain tissue of HIBD and primary cortex neurons. Mechanistically, LOX increases its catalytic substrates, the Collagen I/III components, promoting extracellular matrix (ECM) remodeling and possibly mediating ECM cross-linking, which leads to increased stiffness at the site of injury and subsequent activation of the Piezo1 channel. Piezo1 senses these stiffness stimuli and then induces neuronal ferroptosis in a GPX4-dependent manner. Pharmacological inhibition of LOX or Piezo1 ameliorated brain neuronal ferroptosis and improved learning and memory impairments. Furthermore, we identified traumatic acid (TA) as a novel LOX inhibitor that effectively suppresses LOX enzymatic activity, mitigating neuronal ferroptosis and promoting synaptic plasticity. In conclusion, our findings elucidate a critical role for LOX-mediated ECM mechanical stress-induced Piezo1 activation in regulating ferroptotic cell death in HIBD. This mechanistic insight provides a basis for developing targeted therapies aimed at ameliorating neurological outcomes in neonates affected by HIBD.

Correlation study of multiple inflammatory indices and vertebral compression fracture: A cross-sectional study.

Background: Vertebral compression fractures (VCFs) are prevalent in patients with osteoporosis and pose significant health risks. Although chronic low-grade inflammation plays a crucial role in the pathogenesis of osteoporosis, the relationship between various inflammatory indices and the occurrence of fractures remains unclear. Objective: This study aims to evaluate the correlation between multiple inflammatory indices, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), and VCFs, to explore the significance of these indices in clinical application. Methods: Clinical data of 310 patients diagnosed with osteoporosis from November 2020 to June 2023 in the hospital were collected. The general conditions between fracture and non-fracture groups were described. Spearman analysis and binary logistic regression analysis were used to assess the relationship between inflammatory indices and VCFs. Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of these inflammatory indices for VCFs. Results: VCFs were diagnosed in 43.55 % of patients with osteoporosis. NLR(ρ = 0.169, P=0.003), MLR(ρ = 0.293, P<0.001), SII(ρ = 0.126, P=0.027), and SIRI(ρ = 0.273, P<0.001) were positively correlated with the occurrence of VCFs. NLR(OR=1.480, 95 %CI 1.114 âˆ¼ 1.966, P=0.007), MLR(multiplied by 100, OR=1.048, 95 %CI 1.011 âˆ¼ 1.087, P=0.011), and SIRI(OR=3.327, 95 %CI 1.510 âˆ¼ 7.330, P=0.003) were independent risk factors for VCFs, hip bone mineral density (BMD) (OR=0.011, 95 %CI 0.001 âˆ¼ 0.151, P=0.001) was an independent protective factor for VCFs. MLR(AUC 0.671, 95 % CI=0.610 âˆ¼ 0.732, P <0.001) had relatively high clinical diagnostic efficacy. Conclusion: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI) are independent risk factors for vertebral compression fractures.

Comparative transcriptome analysis reveals molecular mechanisms of the effects of light intensity and photoperiod on ovarian development in Procambarus clarkii (Girard, 1852).

Procambarus clarkii (Girard, 1852) has important economic value in China and internationally. In this research, the comparative transcriptome analysis was used to reveal molecular mechanisms of influences of photoperiod and light intensity on ovarian development in P. clarkii for the first time. Some genes (such as laminin, collagen, integrin beta, catenin) and pathways (including TGF-beta signaling pathway, focal adhesion, ECM-receptor interaction) associated with ovarian development and oocyte maturation were significantly upregulated. Some genes related to circadian clock (such as CLK, PER) were identified in this research. The results indicated that when light intensity or photoperiod increased, P. clarkii could up-regulate the expression levels of the laminin and collagen, thereby synthesizing related proteins, promoting meiosis of the oocytes, thus increasing the number of oocytes in the ovary. At the same time, P. clarkii could up-regulate the expression levels of integrin beta, integrin alpha 6, and diacylglycerol to synthesize related proteins, thereby promoting the formation of proteins and fats such as triglycerides, these proteins and fats can provide material basis for maturation and development of oocytes, resulting in oocyte maturation and ovarian development. P. clarkii could synthesize related proteins by upregulating expression levels of genes (such as catenin), these proteins or hormones can adhere to other actins (such as integrins), thereby stabilizing the morphology of the oocytes and ensuring normal development. Meantime, the increase in light intensity or photoperiod could cause release GSH and VTG, resulting in oocytes development and maturation. The data in this research can reveal molecular mechanisms of impacts of photoperiod and light intensity on oocyte maturation and ovarian development in P. clarkii, can offer crucial genomic data for studying developmental mechanisms of ovary and oocyte in crustacean.

Comparison of the short-term efficacy of MIS-TLIF and Endo-LIF for the treatment of two-segment lumbar degenerative disease.

BACKGROUND: This study retrospectively compared short-term clinical outcomes and complications of minimally invasive surgery transforaminal lumbar interbody fusion(MIS-TLIF)and endoscopic lumbar interbody fusion(Endo-LIF))for two-segmental lumbar degenerative disease, aiming to guide spine surgeons in selecting surgical approaches. METHODS: From January 2019 to December 2023, 30 patients were enrolled,15 in the MIS-TLIF group and 15 in the Endo-LIF group. All patients were followed up for more than 3 months after surgery and the following information was recorded: (1)surgery time, difference in hemoglobin between preoperative and postoperative, surgical costs, first time out of bed after operation, postoperative hospitalization time, postoperative complication; (2) ODI score (The Oswestry Disability Index), leg and back VAS score (Visual Analogue Scale), and lumbar vertebra JOA score (Japanese Orthopaedic Association Scores); (3) MacNab score at final follow-up to assess clinical outcome, CT to evaluate lumbar fusion. RESULTS: There were significant differences between the two groups regarding operation time and cost, with the MIS-TLIF group performing significantly better. Intraoperative bleeding was considerably less in the Endo-LIF group compared to the MIS-TLIF group. However, there were no significant differences in the time of the first postoperative ambulation, postoperative hospitalization time, and postoperative complications. There was no significant difference in preoperative VAS, ODI, and JOA between the two surgical groups There were no significant differences in VAS(leg), ODI, and JOA scores between the two groups before and at 1 day,7 days, 1 month, 3 months and final follow-up. However, at 1 day postoperatively, the VAS( back)score in the Endo-LIF group was lower than that in the MIS-TLIF group, and the difference was statistically significant. At the final follow-up, all patients achieved grade III and above according to the Bridwell criteria, and there was no significant difference between the two surgical groups compared to each other. According to the MacNab score at the final follow-up, the excellent rate was 80.00% in the Endo-LIF group and 73.33% in the MIS-TLIF group, with no significant difference between the two groups. CONCLUSION: There was no significant difference in short-term efficacy and safety between Endo-LIF and MIS-TLIF for two-segment degenerative lumbar diseases. MIS-TLIF has a shorter operative time and lower costs, while Endo-LIF causes less tissue damage, blood loss, and early postoperative pain, aiding long-term recovery. Both MIS-TLIF and Endo-LIF are promising for treating two-segment lumbar degenerative disease. The choice of a surgical procedure depends on the patient's financial situation, their ability to tolerate surgery, and the surgeon's expertise.

Fine-tuning of IPA1 transactivation activity by E3 ligase IPI7-mediated non-proteolytic K29-ubiquitination during Magnaporthe oryzae infection.

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Endoscopic transnasal prelacrimal recess approach via the orbital floor to the infraorbital region: an anatomical study.

PURPOSE: The aim of this study is to describe the maximum exposure of the infraorbital region via the orbital floor using the transnasal prelacrimal recess approach (PLRA), and to provide an anatomical basis for treating lesions in the infraorbital region. METHODS: Ten freshly injected frozen heads were dissected using the PLRA. The orbital floor was removed along the border of the medial infraorbital quadrangle, and the periorbita was opened to expose the infraorbital region. The areas of the medial infraorbital quadrangles were measured and analyzed. The PLRA was applied separately on the left and right sides of each cadaver head, resulting in a total of 20 prelacrimal recess approaches. RESULTS: The PLRA enabled visualization of the optic nerve and the central retinal artery through the orbital floor. By integrating both medial and lateral approaches in relation to the inferior rectus muscle, all crucial anatomical structures within the infraorbital region could be clearly identified. The area of the medial infraorbital quadrangle was 420.65 ± 24.03 mm2. CONCLUSION: The PLRA provides access through the orbital floor to the maximum boundary of the infraorbital region, including the lateral orbital wall at the outermost level, the superior rectus muscle at the topmost level, and the medial orbital wall at the innermost level.

A machine learning based EMA-DCPM algorithm for production scheduling.

Some special manufacturing fields such as aerospace may encounter mixed production of multiple research and development projects and multiple batch production projects. Under these special production conditions resource conflicts are more severe, resulting in uncertain operating times that are difficult to predict. In addition, a single project may have tens of thousands of supporting products, making it difficult to effectively control the total construction process. To address these challenges this paper proposes new methods. A model, EMA-DCPM (dynamic critical path method) incorporating attention mechanisms in Enterprise Resource Planning and Mechanical Engineering Society) has been proposed. This model predicts product job time through machine learning methods and discovers the predictive advantage of the attention mechanism through data comparison. The CPM control algorithm was improved to enhance its robustness and an efficient modeling method, "5+X" was proposed. This new method is suitable for mixed line planning management in sophisticated manufacturing projects and has value for practical applications.

Phosphorous accumulation associated with mitochondrial PHT3-mediated enhanced arsenate tolerance in Chlamydomonas reinhardtii.

Arsenate is a highly toxic element and excessive accumulation of arsenic in the aquatic environment easily triggers a problem threatening the ecological health. Phytoremediation has been widely explored as a method to alleviate As contamination. Here, the green algae, Chlamydomonas reinhardtii was investigated by profiling the accumulation of arsenate and phosphorus, which share the same uptake pathway, in response to arsenic stress. Both C. reinhardtii wild type C30 and the Crpht3 mutant were cultured under arsenic stress, and demonstrated a similar growth phenotype under limited phosphate supply. Sufficient phosphate obviously increased the uptake of polyphosphate and intercellular phosphate in the Crpht3 mutant, which increased the arsenic tolerance of the Crpht3 mutant under stress from 500 µmol L-1 As(V). Upregulation of the PHT3 gene in the Crpht3 mutant increased accumulation of phosphate in the cytoplasm under arsenate stress, which triggered a regulatory role for the differentially expressed genes that mediated improvement of the glutathione redox cycle, antioxidant activity and detoxification. While the wild type C30 showed weak arsenate tolerance because of little phosphate accumulation. These results suggest that the enhanced arsenic tolerance of the Crpht3 mutant is regulated by the PHT3 gene mediation. This study provides insight onto the responsive mechanisms of the PHT3 gene-mediated in alleviating arsenic toxicity in plants.

[Effect of Peitu Yifei Granules on autophagy mechanism in rats with idiopathic pulmonary fibrosis based on PI3K/Akt/mTOR signaling pathway].

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

Cadmium Minimization in Grains of Maize and Wheat Grown on Smelting-Impacted Land Ameliorated by Limestone.

Cadmium (Cd) contamination in agricultural soils has emerged as a significant concern, particularly due to its potential impact on plant-based food. Soil pH reductions can exacerbate Cd mobility, leading to excessive accumulation in crops. While liming has been demonstrated as an effective method to mitigate Cd accumulation in rice grains in acid soils of southern China, its efficacy in remediating acid soils in northern China remains unclear. In this study, a multi-year field experiment was conducted on farmland impacted by zinc ore smelting at coordinates of 33.92° N 112.46° E to investigate the use of limestone for controlling Cd accumulation in wheat and maize grains. The results indicated that applying 7.5 t ha-1 of limestone significantly raised the soil pH from 4.5 to 6.8 as anticipated. Different rates of limestone application (2.25, 4.45, and 7.50 t ha-1) reduced Cd bioavailability in the soil by 20-54%, and Cd accumulation in wheat grains by 5-38% and maize grains by 21-63%, without yield penalty. The remediation effects were sustained for at least 27 months, highlighting limestone as a promising ameliorant for smelting-affected farmland in northern China.

Networked dynamic systems with higher-order interactions: stability versus complexity.

The stability of complex systems is profoundly affected by underlying structures, which are often modeled as networks where nodes indicate system components and edges indicate pairwise interactions between nodes. However, such networks cannot encode the overall complexity of networked systems with higher-order interactions among more than two nodes. Set structures provide a natural description of pairwise and higher-order interactions where nodes are grouped into multiple sets based on their shared traits. Here we derive the stability criteria for networked systems with higher-order interactions by employing set structures. In particular, we provide a simple rule showing that the higher-order interactions play a double-sided role in community stability-networked systems with set structures are stabilized if the expected number of common sets for any two nodes is less than one. Moreover, although previous knowledge suggests that more interactions (i.e. complexity) destabilize networked systems, we report that, with higher-order interactions, networked systems can be stabilized by forming more local sets. Our findings are robust with respect to degree heterogeneous structures, diverse equilibrium states and interaction types.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

The OsGAPC1-OsSGL module negatively regulates salt tolerance by mediating abscisic acid biosynthesis in rice.

Plants frequently encounter adverse conditions and stress during their lives. Abscisic acid (ABA) plays a crucial role in response to salt stress, and dynamic regulation of ABA levels is essential for plant growth and stress resistance. In this study, we identified a transcription factor, OsSGL (Oryza sativa Stress tolerance and Grain Length), which acts as a negative regulator in salt stress, controlling ABA synthesis. OsSGL-overexpressing and mutant materials exhibited sensitivity and tolerance to salt stress, respectively. Notably, under salt treatment, several ABA-related genes, including the ABA synthesis enzyme OsNCED3 and the ABA response gene OsRAB21, were bound by OsSGL, leading to the inhibition of their transcription. Additionally, we found that a key enzyme involved in glycolysis, OsGAPC1, interacted with OsSGL and enhanced the inhibitory effect of OsSGL on OsNCED3. Upon salt stress, OsGAPC1 underwent acetylation and then translocated from the nucleus to the cytoplasm, partially alleviating the inhibitory effect of OsSGL on OsNCED3. Identification of the OsGAPC1-OsSGL module revealed a negative regulatory mechanism involved in the response of rice to salt stress. This discovery provides insight into the dynamic regulation of ABA synthesis in plants under salt stress conditions, highlighting the delicate balance between stress resistance and growth regulation.

Identification of Active Molecules against Thrombocytopenia through Machine Learning.

Thrombocytopenia, which is associated with thrombopoietin (TPO) deficiency, presents very limited treatment options and can lead to life-threatening complications. Discovering new therapeutic agents against thrombocytopenia has proven to be a challenging task using traditional screening approaches. Fortunately, machine learning (ML) techniques offer a rapid avenue for exploring chemical space, thereby increasing the likelihood of uncovering new drug candidates. In this study, we focused on computational modeling for drug-induced megakaryocyte differentiation and platelet production using ML methods, aiming to gain insights into the structural characteristics of hematopoietic activity. We developed 112 different classifiers by combining eight ML algorithms with 14 molecule features. The top-performing model achieved good results on both 5-fold cross-validation (with an accuracy of 81.6% and MCC value of 0.589) and external validation (with an accuracy of 83.1% and MCC value of 0.642). Additionally, by leveraging the Shapley additive explanations method, the best model provided quantitative assessments of molecular properties and structures that significantly contributed to the predictions. Furthermore, we employed an ensemble strategy to integrate predictions from multiple models and performed in silico predictions for new molecules with potential activity against thrombocytopenia, sourced from traditional Chinese medicine and the Drug Repurposing Hub. The findings of this study could offer valuable insights into the structural characteristics and computational prediction of thrombopoiesis inducers.