Association of sleep quality with cognitive dysfunction in middle-aged and elderly adults: a cross-sectional study in China.

Objectives: Sleep is an indispensable part of human health, which can help us to restore physical strength, enhance immunity and maintain nervous system stability. The relationship between sleep quality and cognitive dysfunction is unclear, especially at the community population level. This study aims to explore the association between sleep quality and cognitive dysfunction. Methods: A total of 5,224 community residents were enrolled in this cross-sectional study. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Sleep quality was assessed by the multidimensional sleep questionnaire. Multivariate logistic regression was used to analyze the association between sleep quality and cognitive dysfunction. The adjusted models took into account relevant demographic, clinical, and sleep variables. Results: A total of 3,106 participants were enrolled in this study, of whom 463 (15%) had cognitive dysfunction. Total sleep duration, staying up, sleep latency, number of awakenings, and history of sleep medications were associated with cognitive dysfunction in unadjusted models, and these effects were consistent after adjustment. First, those who slept 6-7.9 h per day (OR = 0.57, 95% CI 0.40 to 0.80, p = 0.001) had a lower risk for cognitive dysfunction compared to those who slept less than 6 h per day. Second, participants who stayed up more than 10 times over the 3 months (OR = 1.90, 95% CI 1.20 to 3.00, p = 0.006) were more likely to suffer cognitive dysfunction than those who never stayed up. Third, we also found that participants with sleep latencies of 16-30 min were less likely to experience cognitive dysfunction than those with sleep latencies of less than 16 min after adjusting confounders (OR = 0.33, 95% CI 0.23 to 0.47, p < 0.001). Fourth, participants who woke up once (OR = 1.65, 95% CI 1.19 to 2.30, p = 0.003) and three or more times (OR = 2.34, 95% CI 1.25 to 4.36, p = 0.008) after falling asleep had a higher risk than those who did not wake up at night. Last, participants taking sleep medication (OR = 2.97, 95% CI 1.19 to 7.45, p = 0.020) were more vulnerable to cognitive dysfunction, relative to participants without taking any medications. Conclusion: Our results suggest that after adjustment for potential confounding variables, poor sleep quality is associated with cognitive dysfunction.

Periampullary duodenal neuroendocrine tumor in a patient with neurofibromatosis-1: A case report.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are exposed to a higher risk of developing neuroendocrine tumors (NETs). Periampullary neuroendocrine neoplasms (NENs) in NF1 patients primarily affect the duodenum and periampullary region. CASE SUMMARY: A 50-year-old male patient was admitted to our hospital due to progressive skin and scleral yellowing for over 6 months. An abdominal contrast-enhanced computed tomography scan revealed a tumor in the periampullary region, which measured 1.2 cm × 1.4 cm in size and showed a progressive enhancement. Magnetic resonance cholangiopancreatography indicated the dilation of intrahepatic and extrahepatic bile ducts. The patient was diagnosed with an ampullary tumor with the possibility of malignancy. A Whipple procedure was performed. Microscopically, the duodenum tumor was found to invade the mucosa, sphincter, and muscular layer of the duodenal papilla. Histologic hematoxylin and eosin staining confirmed the presence of duodenal G1 NET. Subsequently, a bibliometric analysis was performed to evaluate the state of NEN research. Publications about periampullary NENs showed an annual increase, with most of them focusing on the treatment and diagnosis of NENs. CONCLUSION: This article reported a case of periampullary duodenal NET in a patient with NF1, and a bibliometric analysis was conducted.

The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with statins in patients with hypercholesterolemia: a network meta-analysis.

Background: In recent years, the position of PCSK9 inhibitors as adjuvant therapy to statins in guidelines has further improved. However, there remained a dearth of direct comparative studies among different PCSK9 inhibitors. Therefore, this study aimed to conduct a network meta-analysis to evaluate the efficacy and safety of different PCSK9 inhibitors combined with statins. Methods: A comprehensive literature search was conducted from the study's inception to 12 November 2023, encompassing multiple online databases including PubMed, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov to obtain relevant randomized controlled trials. Frequentist network meta-analysis was employed to compare the efficacy and safety of different PCSK9 inhibitors. The efficacy endpoints were low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)). The safety endpoints were any adverse events (AE), severe adverse events (SAE), AE leading to treatment discontinuation, and injection-site reaction. Results: Compared with placebo and ezetimibe, all PCSK9 inhibitors demonstrated significant reductions in LDL-C levels. Notably, evolocumab exhibited the most pronounced effect with a treatment difference of -63.67% (-68.47% to -58.87%) compared with placebo. Regarding dosage selection for evolocumab, the regimen of 140 mg Q2W (-69.13%, -74.55% to -63.72%) was superior to 420 mg QM (-61.51%, -65.97% to -57.05%). Based on rankings and P-scores analysis, tafolecimab 150 mg Q2W demonstrated superior efficacy in reducing ApoB levels (-61.70%, -84.38% to -39.02%) and Lp(a) levels (-43%, 30%, -68%, 81% to -17%, 79%). Furthermore, the safety profile of PCSK9 inhibitors was favorable with no increase in the incidence of AE, SAE, or AE leading to treatment discontinuation; however, alirocumab, inclisiran, and tafolecimab may potentially entail a potential risk associated with injection-site reactions. Conclusion: Compared with placebo and ezetimibe, PCSK9 inhibitors can significantly reduce LDL-C, ApoB, and Lp(a) when combined with statins to treat hypercholesterolemia. Furthermore, PCSK9 inhibitors and ezetimibe exhibit similar safety profiles. Systematic Review Registration: [PROSPERO], identifier [CRD42023490506].

Corrigendum: Study on the effects of intestinal flora on gouty arthritis.

[This corrects the article DOI: 10.3389/fcimb.2024.1341953.].

Sonication-Assisted Electrochemical Synthesis of Silver Nanoparticles.

In this work, we propose a method for synthesizing silver nanoparticles (Ag NPs) utilizing a sonication-assisted electrochemical approach with a common ultrasonic cleaner. Silver nitrate is employed as the precursor and polyvinylpyrrolidone functions as the ligand. The incorporation of sonication is identified as crucial for achieving several benefits such as enhanced mass transfer, improved dispersion of reactants, and the prevention of electrode fouling. Optimized sonication and electrochemical conditions synergistically contribute to a higher yield of well-dispersed Ag NPs, which are characterized by an average size of 10 nm. Furthermore, the electrode's suitability for the continuous synthesis of Ag NPs over an extended period is highlighted owing to effective electrode surface cleaning facilitated by sonication. This cleaning process proves to be essential in maintaining the electrochemical activity of the electrode, ensuring consistency in the synthesis process. The proposed sonication-assisted electrochemical synthesis method not only addresses challenges associated with electrode fouling but also significantly enhances the dispersity and yield of the resulting particles, making it valuable for scalability and practical applications in various fields, including sensors, catalysis, and nanotechnology.

Salidroside sensitizes Triple-negative breast cancer to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy.

INTRODUCTION: Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. OBJECTIVE: This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. METHODS: Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. RESULTS: The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. CONCLUSIONS: Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.

PAIP1 binds to pre-mRNA and regulates alternative splicing of cancer pathway genes including VEGFA.

BACKGROUND: Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the mechanisms of the PAIP1 regulation in tumor cells remain poorly understood. RESULTS: Here, we used a recently developed UV cross-linking and RNA immunoprecipitation method (iRIP-seq) to map the direct and indirect interaction sites between PAIP1 and RNA on a transcriptome-wide level in HeLa cells. We found that PAIP1 not only binds to 3'UTRs, but also to pre-mRNAs/mRNAs with a strong bias towards the coding region and intron. PAIP1 binding sites are enriched in splicing enhancer consensus GA-rich motifs. RNA-seq analysis revealed that PAIP1 selectively modulates the alternative splicing of genes in some cancer hallmarks including cell migration, the mTOR signaling pathway and the HIF-1 signaling pathway. PAIP1-regulated alternative splicing events were strongly associated with PAIP1 binding, demonstrating that the binding may promote selection of the nearby splice sites. Deletion of a PAIP1 binding site containing seven repeats of GA motif reduced the PAIP1-mediated suppression of the exon 6 inclusion in a VEGFA mRNA isoform. Proteomic analysis of the PAIP1-interacted proteins revealed the enrichment of the spliceosome components and splicing factors. CONCLUSIONS: These findings suggest that PAIP1 is both a polyadenylation and alternative splicing regulator, that may play a large role in RNA processing via its role in alternative splicing regulation.

Purification Resistance Index: A new water quality assessment method toward drinking water production.

Water quality assessment plays a significant role in ensuring the availability of clean and safe water. The Water Quality Index (WQI) model method has been developed to provide a basis for assessing water quality by integrating various water quality parameters. However, existing WQIs do not "actively" consider the difficulty of water treatment from raw water to specific water use scenarios. This study proposes a novel model framework, named as Purification Resistance Index (PRI), quantitatively evaluating not only the exceedance of pollutants but also how difficult they can be removed in the water treatment process. The framework is built based on the conventional drinking water treatment processes, with sub-indices for coagulation-sedimentation (rc), filtration (rf), disinfection (rd), and advanced treatment (ra). The model considers appropriate weights assigned to each sub-index to calculate the purification resistance, resulting in a comprehensive index for water quality evaluation. Case studies on nationwide and citywide water source reservoirs demonstrated the applicability of PRI approach. PRI breakthrough the traditional water quality risk assessment paradigm and extents to engineering region and provide useful tools for water source supervision, drinking water treatment plant planning and updating, operation control, and other purposes. Water authority, water utility and municipal design institute will all benefit. It is open for more localized practices validation and discussion.

Principle and Logic of Vertical Reduction Repair Double-Ring Breast Reduction.

BACKGROUND: Secondary reduction mammaplasty poses challenges. OBJECTIVES: This article delves into the reasons and complaints regarding secondary repair following double-ring method and outlines the principle and logic of utilizing vertical incision for repair. METHODS: A retrospective analysis of patients who underwent secondary reduction mammaplasty in our hospital was conducted. The analysis included baseline demographic data, reasons for consultation, surgical records, and postoperative outcomes. RESULTS: Thirty-five patients (70 breasts) underwent secondary reduction mammaplasty. The mean time between the primary reduction mammaplasty and second procedure was 2.99 years (range, 0.5-15years). The mean weights were 210.49g (range, 42-558g) and 207.91g (range, 6-560g) for left and right mastectomies, respectively. Reasons for secondary reduction mammaplasty include poor shape (flat breasts and pseudoptosis), widened incision scar, persistent macromastia, and bilateral asymmetry. CONCLUSIONS: The superior and superomedial vertical techniques are safe, effective, and satisfactory in secondary reduction mammaplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

[Separation/Conversion Disorders in Functional Coma With Pseudocataplexy: Report of One Case and Literature Review].

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.

Computed tomography-based intermuscular adipose tissue analysis and its predicting role in post-kidney transplantation diabetes mellitus.

BACKGROUND: While body mass index (BMI) is the most widely used indicator as a measure of obesity factors in post-transplantation diabetes mellitus (PTDM), body composition is a more accurate measure of obesity. This study aims to investigate the effects of Computed tomography (CT)--based morphemic factors on PTDM and establish a prediction model for PTDM after kidney transplantation. METHODS: The pre-transplant data and glycemic levels of kidney transplant recipients (June 2021 to July 2023) were retrospectively and prospectively collected. Univariate and multivariate analyses were conducted to analyze the relationship between morphemic factors and PTDM at one month, six months, and one year after hospital discharge. Subsequently, a one-year risk prediction model based on morphemic factors was developed. RESULTS: The study consisted of 131 participants in the one-month group, where Hemoglobin A1c (HbA1c) (p = 0.02) was identified as the risk factor for PTDM. In the six-month group, 129 participants were included, and the intermuscular adipose tissue (IMAT) area (p = 0.02) was identified as the risk factor for PTDM. The one-year group had 128 participants, and the risk factors for PTDM were identified as body mass index (BMI) (p = 0.02), HbA1c (p = 0.01), and IMAT area (p = 0.007). HbA1c (%) and IMAT area were included in the risk prediction Model for PTDM in the one-year group with AUC = 0.716 (95 % CI 0.591-0.841, p = 0.001). CONCLUSIONS: Compared to BMI and other morphemic factors, this study demonstrated that the IMAT area was the most potential predictor of PTDM. CLINICAL TRIAL NOTATION: Chictr.org (ChiCTR2300078639).

NLRP3 Inflammasome Inhibition After Pilocarpine-Induced Status Epilepticus Attenuates Chronic Inflammation in Epileptic Mice.

Objective: To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE). Methods: Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE. Results: Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses. Conclusion: Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain.

Combinatorial accumulation, stress response, detoxification and synaptic transmission effects of cadmium and selenium in clams Ruditapes philippinarum.

This study investigated the toxicological effects and mechanisms of cadmium (Cd) (5 and 50 µg/L) and selenium (Se) (3 and 30 µg/L) at environmentally relevant concentrations on the gills and digestive glands of clams Ruditapes philippinarum. Results indicated that Cd and Se could tissue-specifically impact osmoregulation, energy metabolism, and synaptic transmission in the gills and digestive glands of clams. After exposure to 50 µg/L Cd, the digestive glands of clams up-regulated the expression of methionine-gamma-lyase and metallothionein for detoxification. Clam digestive glands exposed to 3 µg/L Se up-regulated the expression of catalase and glutathione peroxidase to alleviate oxidative stress, and down-regulated the expression of selenide-water dikinase to reduce the conversion of inorganic Se. Additionally, the interaction mode between Cd and Se largely depended on their molar ratio, with a ratio of 11.71 (50 µg/L Cd + 3 µg/L Se) demonstrated to be particularly harmful, as manifested by significantly more lesions, oxidative stress, and detoxification demand in clams than those exposed to Cd or Se alone. Collectively, this study revealed the complex interaction patterns and mechanisms of Cd and Se on clams, providing a reference for exploring their single and combined toxicity.

Identification of ribosome biogenesis genes and subgroups in ischaemic stroke.

Background: Ischaemic stroke is a leading cause of death and severe disability worldwide. Given the importance of protein synthesis in the inflammatory response and neuronal repair and regeneration after stroke, and that proteins are acquired by ribosomal translation of mRNA, it has been theorised that ribosome biogenesis may have an impact on promoting and facilitating recovery after stroke. However, the relationship between stroke and ribosome biogenesis has not been investigated. Methods: In the present study, a ribosome biogenesis gene signature (RSG) was developed using Cox and least absolute shrinkage and selection operator (LASSO) analysis. We classified ischaemic stroke patients into high-risk and low-risk groups using the obtained relevant genes, and further elucidated the immune infiltration of the disease using ssGSEA, which clarified the close relationship between ischaemic stroke and immune subgroups. The concentration of related proteins in the serum of stroke patients was determined by ELISA, and the patients were divided into groups to evaluate the effect of the ribosome biogenesis gene on patients. Through bioinformatics analysis, we identified potential IS-RSGs and explored future therapeutic targets, thereby facilitating the development of more effective therapeutic strategies and novel drugs against potential therapeutic targets in ischaemic stroke. Results: We obtained a set of 12 ribosome biogenesis-related genes (EXOSC5, MRPS11, MRPS7, RNASEL, RPF1, RPS28, C1QBP, GAR1, GRWD1, PELP1, UTP, ERI3), which play a key role in assessing the prognostic risk of ischaemic stroke. Importantly, risk grouping using ribosome biogenesis-related genes was also closely associated with important signaling pathways in stroke. ELISA detected the expression of C1QBP, RPS28 and RNASEL proteins in stroke patients, and the proportion of neutrophils was significantly increased in the high-risk group. Conclusions: The present study demonstrates the involvement of ribosomal biogenesis genes in the pathogenesis of ischaemic stroke, providing novel insights into the underlying pathogenic mechanisms and potential therapeutic strategies for ischaemic stroke.

Modeling the impact of pesticide drift deposition on off-field non-target receptors.

Pesticide application can result in residue drift deposition in off-field areas, which can be harmful to non-target organisms inhabiting adjacent off-field environments. In order to comprehend the impact of pesticide drift deposition on off-field non-target organisms, an integrated modeling approach was incorporated into the life cycle analysis perspective for the assessment of their exposure to pesticide residues and the characterization of their human toxicity and ecotoxicity potentials. The modeling assumption comprises four modeling scenarios: children & cattle & sensitive crops (tomatoes) based on exposure assessment, and the continent-scale human health toxicity & ecotoxicity under a life cycle analysis perspective. The simulation results for the nearby off-field exposure scenario revealed that pesticide dissipation kinetics in environments and drift deposition type were two important factors influencing non-target organisms' exposure to pesticide residues deposited in off-field environments. The continental scenario simulated via USEtox revealed that considering off-field drift deposition resulted in lower simulated human toxicity potentials of pesticides when compared to simulation results that did not consider drift deposition, given that pesticide residues remaining within the treated field contributed the most to overall human exposure. Taking drift deposition into account, on the other hand, could result in higher or lower simulated ecotoxicity potentials of pesticides than not taking drift deposition in off-field areas into account, depending on the physicochemical properties of pesticides. The proposed modeling approach, which is adaptable to drift deposition types and chemical species, can aid in investigating the off-field impacts of pesticide residues. Future research will incorporate spatiotemporal factors to characterize region-specific drift deposition functions and pesticide fate in off-field environments to conduct site-specific impact assessments.

Machine learning phenotyping and GWAS reveal genetic basis of Cd tolerance and absorption in jute.

Cadmium (Cd) is a dangerous environmental contaminant. Jute (Corchorus sp.) is an important natural fiber crop with strong absorption and excellent adaptability to metal-stressed environments, used in the phytoextraction of heavy metals. Understanding the genetic and molecular mechanisms underlying Cd tolerance and accumulation in plants is essential for efficient phytoremediation strategies and breeding novel Cd-tolerant cultivars. Here, machine learning (ML) and hyperspectral imaging (HSI) combining genome-wide association studies (GWAS) and RNA-seq reveal the genetic basis of Cd resistance and absorption in jute. ML needs a small number of plant phenotypes for training and can complete the plant phenotyping of large-scale populations with efficiency and accuracy greater than 90%. In particular, a candidate gene for Cd resistance (COS02g_02406) and a candidate gene (COS06g_03984) associated with Cd absorption are identified in isoflavonoid biosynthesis and ethylene response signaling pathways. COS02g_02406 may enable plants to cope with metal stress by regulating isoflavonoid biosynthesis involved in antioxidant defense and metal chelation. COS06g_03984 promotes the binding of Cd2+ to ETR/ERS, resulting in Cd absorption and tolerance. The results confirm the feasibility of high-throughput phenotyping for studying plant Cd tolerance by combining HSI and ML approaches, facilitating future molecular breeding.

A genetic investigation in five Chinese families with keratoconus.

Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.

The latest research progress: Active components of Traditional Chinese medicine as promising candidates for ovarian cancer therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ovarian cancer ranks the first in the mortality of gynecological tumors. Because there are no obvious symptoms in the early stage of ovarian cancer, most patients are in the advanced stage of the disease at the time of diagnosis. The incidence of ovarian cancer is increasing year by year, and the incidence of ovarian cancer has a trend of younger age. In recent years. Traditional Chinese medicine (TCM) has a significant impact on improving the quality of life of cancer patients, reducing drug toxicity, preventing metastasis and recurrence, enhancing the efficacy of radiotherapy and chemotherapy, and prolonging survival time, so patients have benefited a lot. AIM OF THE STUDY: This review summarizes the mechanisms and molecular pathways through which active ingredients of TCM act in ovarian cancer. It explores the advantages of TCM in treating ovarian cancer. This review provides theoretical support for the use of TCM in the treatment of ovarian cancer, offering new perspectives for its clinical prevention and treatment. MATERIALS AND METHODS: This review conducted a literature search on PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) for relevant studies on TCM active ingredients in preventing ovarian cancer. The search terms included "ovarian cancer" combined with "Chinese herbal medicine," "Herbal medicine," "Traditional Chinese medicine," and "Active ingredients of Chinese medicine". Based on existing experimental and clinical research, the paper systematically summarized and analyzed the mechanisms of TCM in treating ovarian cancer. RESULTS: Active ingredients of TCM inhibit the occurrence and development of ovarian cancer through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, suppressing tumor cell migration and invasion, inducing tumor cell autophagy, promoting epithelial-mesenchymal transition, and enhancing the efficacy of radiotherapy and chemotherapy drugs. Chinese medicine provides a comprehensive treatment option for ovarian cancer patients, synergizing with radiotherapy and chemotherapy drugs to enhance treatment effectiveness and introduce new hope and possibilities in clinical therapy. CONCLUSIONS: Active ingredients of TCM can inhibit the occurrence and development of ovarian cancer, but further clinical research is needed to support their application.