Chemical characteristics and sources apportionment of volatile organic compounds in the primary urban area of Shijiazhuang, North China Plain.

VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources. Results indicated that the TVOCs (total VOCs) concentration was (96.7 ± 63.4 µg/m3), with alkanes exhibiting the highest concentration of (36.1 ± 26.4 µg/m3), followed by OVOCs (16.4 ± 14.4 µg/m3). The key active components were alkenes and aromatics, among which xylene, propylene, toluene, propionaldehyde, acetaldehyde, ethylene, and styrene played crucial roles as reactive species. The sources derived from PMF analysis encompassed vehicle emissions, solvent and coating sources, combustion sources, industrial emissions sources, as well as plant sources, the contribution of which were 37.80%, 27.93%, 16.57%, 15.24%, and 2.46%, respectively. Hence, reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.

Dissolved organic matter characteristics linked to bacterial community succession and nitrogen removal performance in woodchip bioreactors.

Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.

Strategies, techniques and applications for food authentication based on carbohydrates: A review.

The increasing complexity and ubiquity of food processing and the emergence of fraudulent practices have made effective and reliable methods to authenticate food products of utmost importance. Carbohydrates, with various nutritional functions, are abundant in foods and can serve as potential markers for food authentication. However, the complex and diverse structures and properties of carbohydrates, especially polysaccharides, pose challenges. Nonetheless, significant progress has been made in this area. This paper provides an overview of the utilization of carbohydrates in food authentication since 2000, focusing on strategies involving carbohydrate-based markers, carbohydrate profiles, and carbohydrate-protein interaction-based assays. The analytical techniques, applications, challenges and limitations of these strategies are reviewed and discussed. The findings demonstrate that these strategies offer origin verification, quality assessment, adulteration detection, process control, and food species identification. Notably, oligosaccharide analysis has proven effective in food authentication and remains a promising marker, especially for analyzing intricate matrices. The advances in chromatography separation and mass spectrometry identification of isomers and trace amounts of these compounds have facilitated the discovery of such markers. In conclusion, carbohydrate analysis can play a crucial role in food authentication. Future research and development will make the authentication of carbohydrate-rich foods ever more accurate and efficient.

Diterpene glycosides from Fructus Rubi ameliorates benign prostatic hyperplasia in rats through the androgen and TGF-ß/Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Rubi (FR), a food material with medicinal value, is used in traditional Chinese medicine (TCM) for treatment of various kidney-related problems, such as impotence, spermatorrhea, and frequent urination. It is also frequently used to produce diverse functional foods in China. AIM OF STUDY: The purpose of this research was to assess the therapeutic effects of FR diterpene glycosides on RWPE-1 epithelial cell (RWPE-1), a human normal prostatic epithelial cell, and benign prostate hyperplasia (BPH) rats, both of which had been exposed to dihydrotestosterone (DHT) and testosterone propionate (TP), respectively, and to investigate the mechanism of action. METHODS: Target proteins that could stably bind to certain diterpene glycosides were screened through drug affinity responsive target stability combined with mass spectrometry (DARTS/MS). DHT-induced RWPE-1 cells were used to detect drug activity. TP was subcutaneously injected to induce BPH in rats. The extract of diterpene glycosides from FR (FDS) was orally administered for 28 days. The DHT levels in the serum and prostate tissue of the rats were measured through enzyme-linked immunosorbent assay (ELISA), and to analyze cell proliferation and epithelial-mesenchymal transition (EMT), the protein expression of prostate-specific antigen (PSA), androgen receptor (AR), steroid 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen (PCNA), S100 calcium-binding protein A2 (S100A2), transforming growth factor-ß1 (TGF-ß1), E-cadherin, vimentin, and Smad4 was determined through western blotting (WB), immunohistochemistry (IHC), or immunofluorescence (IF). RESULTS: FDS reduced the proliferation of DHT-induced RWPE-1 cells. It also significantly inhibited rat prostate enlargement; decreased DHT levels in the serum and prostate tissue; inhibited the protein expression of AR, PSA, PCNA, S100A2, TGF-ß1, E-cadherin, and Smad4; and increased the protein expression of E-cadherin. CONCLUSION: The present study is the first to report that diterpene glycosides isolated from FR inhibited BPH at the cellular level, regulated the proliferation of prostate cells through the androgen signaling pathway, and prevented EMT in the prostate through the S100A2-mediated TGF-ß/Smad signaling pathway. These results indicate that FDS is a promising multitarget therapy for BPH.

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study.

BACKGROUND: Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. METHODS: Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. RESULTS: There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). CONCLUSIONS: The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

Deciphering the Formation of Fe(IV) in the Fe(II)/Peroxydisulfate Process: The Critical Role of Sulfate Radical.

This study delves into the formation of ferryl ions (Fe(IV)) within the Fe(II)/peroxydisulfate (PDS) process, a pivotal reaction in advanced oxidation processes (AOPs) aimed at organic pollutant removal. Our findings challenge the conventional view that Fe(IV) predominantly forms through oxygen transfer from PDS to Fe(II), revealing that sulfate radicals (SO4•-) play a crucial role in Fe(IV) generation. By employing competitive kinetics, the second-order rate constant for Fe(III) oxidation by SO4•- was quantified as 4.58 × 108 M-1 s-1. Factors such as the probe compound concentration, chloride presence, and iron species influence Fe(IV) generation, all of which were systematically evaluated. Additionally, the study explores Fe(IV) formation in various Fe(II)-activated AOPs, demonstrating that precursors like peroxymonosulfate and H2O2 can also directly oxidize Fe(II) to Fe(IV). Through experimental data, kinetic modeling, and oxygen-18 labeling experiments, this research offers a comprehensive understanding of the Fe(II)/PDS system, facilitating the optimization of AOPs for pollutant degradation. Finally, introducing HSO3- was proposed to shift the Fe(II)/PDS process from Fe(IV)-dominated to SO4•--dominated mechanisms, thereby enhancing pollutant removal efficiencies.

Compromised COPII vesicle trafficking leads to glycogenic hepatopathy in zebrafish.

Being a vital cellular process, COPII vesicle trafficking has been found plays a crucial role in liver metabolism. However, its functions and the underlying mechanisms in systemic metabolic homeostasis have not been fully understood. Here, with a newly identified gene trap zebrafish line (sec31anju221), we show that compromised COPII vesicle trafficking leads to biphasic abnormal hepatic metabolism. During the larval stage, deficiency of COPII-mediated trafficking leads to activation of unfolded protein reaction (UPR) and the development of hepatic steatosis. By using epistasis analysis, we found eIF2a/ATF4 branch serves as the primary effector for liver steatosis. In adult sec31anju221 fish, the hepatosteatosis was reversed and the phenotype swing to glycogenic hepatopathy. Proteomic profiling and biochemical assay indicate sec31anju221 fish are in a state of hypothyroidism. Moreover, our study showed thyroid hormone treatment alleviates the metabolic defects. This study provides insights into processes of liver diseases associated with vesicle trafficking impairments and has expanded our understanding of the pathological interplay between thyroid and liver.

Effect of Alleviating Preoperative Anxiety on Gastrointestinal Function Recovery After Laparoscopic High Ligation of the Hernia Sac in Children with Indirect Inguinal Hernia.

Purpose: Anxiety and depression can affect the physiology of the gastrointestinal tract through the brain-gut axis, causing gastrointestinal dysfunction, which is mainly manifested as indigestion, diarrhoea, constipation, or abdominal pain. Preoperative anxiety arises in children due to separation from parents, fear of unfamiliar surroundings and anaesthesia and surgical procedures.To discuss the effect of alleviating preoperative anxiety on postoperative recovery of gastrointestinal function in children with indirect inguinal hernia after laparoscopic high ligation of the hernia sac. Patients and Methods: 90 children with laparoscopic high ligation of the herniated sac in oblique inguinal hernia were randomly divided into control group (Group C) and experimental group (Group M). The Group M was given midazolam oral solution 0.5mg/kg (maximum dose 20mg), and The Group C was given 5% glucose solution with the same dose.Primary outcome was the time to first postoperative defecation and I-FEED scores.The secondary outcomes included mYPAS-SF scores; child sedation scores; child-parent separation scores; parental STAI scores;PHBQ scores;FLACC scores, operative time, and fluid input and surgeon job satisfaction. Results: Compared with Group C, there was a shorter time to first postoperative defecation (P < 0.05), and lower I-FEED scores on postoperative day 1 (P < 0.05). The mYPAS-SF scores, which were significantly different in Group M at T1, T2, and T3 (P < 0.05), parental STAI scores at S1, child sedation scores and child-parent separation scores in T1, and surgeon job satisfaction between the two groups were significantly different (P < 0.05). There were no statistically significant differences in I-FEED scores on days 2 and 3, PHBQ scores, FLACC scores, operative time, and fluid input between the two groups of children (P > 0.05). Conclusion: Preoperative application of midazolam oral solution to relieve preoperative anxiety helps to promote the recovery of postoperative gastrointestinal function in children with indirect inguinal hernia and increases the surgeon job satisfaction.

Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.

In addition to the cardinal motor symptoms, pain is a major non-motor symptom of Parkinson's disease (PD). Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD. But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized. In the present study, we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia. In these mice, both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated. These effects peaked 7 days after 6-OHDA injection. Meanwhile, striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials, enhanced voltage-gated potassium currents, and dysfunction in inwardly rectifying potassium channels and glutamate transporters. Systemic administration of minocycline, a microglia inhibitor, attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum (but not those specific to M2 microglia and A2 astrocytes), attenuated the damage in the nigrostriatal dopaminergic system, and alleviated the motor deficits and mechanical allodynia in parkinsonian mice. By contrast, local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia. This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD.

The ratio of PKM1/PKM2 is the key factor affecting the glucose metabolism and biological function of colorectal cancer cells.

Background: Despite evidence suggesting a significant role of pyruvate kinase muscle isozyme (PKM) in cancer development, its particular function in colorectal cancer (CRC) remains unclear. This study aimed to elucidate the specific role and mechanism of PKM and its isoforms, PKM1 and PKM2, in the progression of CRC. Methods: We analyzed PKM, PKM1, and PKM2 expression in CRC tissues and their correlation with clinicopathological features. Plasmids were constructed to modulate these isoforms' expression in CRC cells. Cellular behavior changes, including glucose metabolism alterations, were assessed using the Seahorse Energy Meter, and the Cell Counting Kit-8 (CCK8) assay to determine the inhibitory concentration of 5-fluorouracil (5-FU) on different CRC cell groups. Results: Our results showed significant PKM overexpression in CRC tissues, which was correlated with negative prognostic factors such as advanced T stages and lymph node metastasis. A lower PKM1/PKM2 ratio was associated with these adverse outcomes. Functionally, PKM1 overexpression decreased cell migration and invasion, increasing 5-FU sensitivity. Conversely, PKM2 overexpression promoted malignant traits and reduced 5-FU sensitivity. Intriguingly, the introduction of glycolysis inhibitors attenuated the impact of PKM on the biological functions of CRC cells, suggesting a glycolysis-dependent mechanism. Conclusions: This study establishes the PKM1/PKM2 ratio as crucial in CRC progression and 5-FU response. PKM1 overexpression reduces CRC malignancy and increases 5-FU sensitivity, while PKM2 does the opposite. Notably, glycolysis inhibitors lessen PKM's impact on CRC cells, highlighting a glycolysis-dependent mechanism. These insights suggest targeting PKM isoforms and glycolysis pathways as a promising CRC therapeutic strategy, potentially enhancing treatment efficacy.

Unveiling the Reaction Mystery Between Lithium Polysulfides and Lithium Metal Anode in Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are widely regarded as one of the most promising next-generation high-energy-density energy storage devices. However, soluble lithium polysulfides (LiPSs) corrode Li metal and deteriorate the cycling stability of Li-S batteries. Understanding the reaction mechanism between LiPSs and Li metal anode is imperative. Herein, the reaction rate and products of LiPSs with Li metal anode, the composition and structure of the as-generated solid electrolyte interphase (SEI), and the mechanism of lithium nitrate (LiNO3) additives for inhibiting the corrosion reactions are systematically unveiled. Concretely, LiPSs react with Li metal anode more rapidly than Li salt and generate a Li2S-rich SEI. The Li2S-rich SEI is highly reactive with LiPSs, which exacerbates the formation of dendritic Li and the continuous corrosion of active Li. LiNO3 functions dominantly by modulating the solvation structure of LiPSs and inherently reducing the reactivity of LiPSs, rather than the conventional understanding of LiNO3 participating in the formation of SEI. This work reveals the reaction mechanism between LiPSs and Li metal anode and inspires rational regulating of the solvation structure of LiPSs for stabilizing Li metal anode in Li-S batteries.

Meta-analysis of efficacy and safety of pembrolizumab for the treatment of advanced or recurrent cervical cancer.

BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.

Lactobacillus Firm-5-derived succinate prevents honeybees from having diabetes-like symptoms.

The gut microbiome plays an important role in honeybee hormonal regulation and growth, but the underlying mechanisms are poorly understood. Here, we showed that the depletion of gut bacteria resulted in reduced expression of insulin-like peptide gene (ilp) in the head, accompanied by metabolic syndromes resembling those of Type 1 diabetes in humans: hyperglycemia, impaired lipid storage, and decreased metabolism. These symptoms were alleviated by gut bacterial inoculation. Gut metabolite profiling revealed that succinate, produced by Lactobacillus Firm-5, played deterministic roles in activating ilp gene expression and in regulating metabolism in honeybees. Notably, we demonstrated that succinate modulates host ilp gene expression through stimulating gut gluconeogenesis, a mechanism resembling that of humans. This study presents evidence for the role of gut metabolite in modulating host metabolism and contributes to the understanding of the interactions between gut microbiome and bee hosts.

The STAT1-SLC31A1 axis: Potential regulation of cuproptosis in diabetic retinopathy.

BACKGROUND: By identifying molecular biological markers linked to cuproptosis in diabetic retinopathy (DR), new pathobiological pathways and more accessible diagnostic markers can be developed. METHODS: The datasets related to DR were acquired from the Gene Expression Omnibus database, while genes associated with cuproptosis were sourced from previously published compilations. Consensus clustering was conducted to delineate distinct DR subclasses. Feature genes were identified utilizing weighted correlation network analysis (WGCNA). Additionally, two machine-learning algorithms were employed to refine the selection of feature genes. Finally, we conducted preliminary validation experiments to ascertain the involvement of cuproptosis in DR development and the transcriptional regulation of critical genes using both the streptozotocin-induced diabetic mouse model and the high glucose-induced BV2 model. RESULTS: In the STZ-induced diabetic mouse retinas, a decrease in the expression of cuproptosis signature proteins (FDX1, DLAT, and NDUFS8) suggested the occurrence of cuproptosis in DR. Subsequently, the expression of eight cuproptosis differential genes was validated through the STZ-induced diabetes and oxygen-induced retinopathy (OIR) models, with the key gene SLC31A1 showing upregulation in both models and dataset species. Further analyses, including weighted gene co-expression network analysis, GSVA, and immune infiltration analysis, indicated a close correlation between cuproptosis and microglia function. Additionally, validation in an in vitro model of microglia indicated the occurrence of cuproptosis in microglia under high glucose conditions, alongside abnormal expression of STAT1 with SLC31A1. CONCLUSION: Our findings suggest that STAT1/SLC31A1 may pave the way for a deeper comprehension of the mechanistic basis of DR and offer potential therapeutic avenues.

Toxicity to the Male Reproductive System after Exposure to Polystyrene Nanoplastics: A Macrogenomic and Metabolomic Analysis.

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs.

Psychiatric Symptoms, Cognition, and Symptom Severity in Children.

Importance: Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms. Objective: To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children. Design, Setting, and Participants: A total of 5175 children with complete data at 2 time points assessed 2 years apart (aged 9 to 11 years at the first assessment) from the ongoing Adolescent Brain and Cognitive Development (ABCD) study were evaluated for a general cognition factor and mental health symptoms from September 2016 to August 2020 at 21 sites across the US. Polynomial and generalized additive models afforded derivation of continuous associations between cognition and psychiatric symptoms across different ranges of symptom severity. Data were analyzed from December 2022 to April 2024. Main Outcomes and Measures: Aggregate cognitive test scores (general cognition) were primarily evaluated in relation to total and subscale-specific symptoms reported from the Child Behavioral Checklist. Results: The sample included 5175 children (2713 male [52.4%] and 2462 female [47.6%]; mean [SD] age, 10.9 [1.18] years). Previously reported mixed findings regarding the association between general cognition and symptoms may consist of several underlying, opposed associations that depend on the class and severity of symptoms. Linear models recovered differing associations between general cognition and mental health symptoms, depending on the range of symptom severities queried. Nonlinear models confirm that internalizing symptoms were significantly positively associated with cognition at low symptom burdens higher cognition = more symptoms) and significantly negatively associated with cognition at high symptom burdens. Conclusions and Relevance: The association between mental health symptoms and general cognition in this study was nonlinear. Internalizing symptoms were both positively and negatively associated with general cognition at a significant level, depending on the range of symptom severities queried in the analysis sample. These results appear to reconcile mixed findings in prior studies, which implicitly assume that symptom severity tracks linearly with cognitive ability across the entire spectrum of mental health. As the association between cognition and symptoms may be opposite in low vs high symptom severity samples, these results reveal the necessity of clinical enrichment in studies of cognitive impairment.

Unraveling the impact of perfluorooctanoic acid on sulfur-based autotrophic denitrification process.

PFOA has garnered heightened scrutiny for its impact on denitrification, especially given its frequent detection in secondary effluent discharged from wastewater treatment plants. However, it is still unclear what potential risk PFOA release poses to a typical advanced treatment process, especially the sulfur-based autotrophic denitrification (SAD) process. In this study, different PFOA concentration were tested to explore their impact on denitrification kinetics and microbial dynamic responses of the SAD process. The results showed that an increase PFOA concentration from 0 to 1000 µg/L resulted in a decrease in nitrate removal rate from 9.52 to 7.73 mg-N/L·h. At the same time, it increased nitrite accumulation and N2O emission by 6.11 and 2.03 times, respectively. The inhibitory effect of PFOA on nitrate and nitrite reductase activity in the SAD process was linked to the observed fluctuations in nitrate and nitrite levels. It is noteworthy that nitrite reductase was more vulnerable to the influence of PFOA than nitrate reductase. Furthermore, PFOA showed a significant impact on gene expression and microbial community. Metabolic function prediction revealed a notable decrease in nitrogen metabolism and an increase in sulfur metabolism under PFOA exposure. This study highlights that PFOA has a considerable inhibitory effect on SAD performance.

circRNA18_46222157_46248185 inhibits melanogenesis by targeting miR-211/EP300 pathway in goat melanocytes.

Objective: This study investigated the effects of circRNA18_46222157_46248185 (named circRNA18) on goat melanogenesis, which differs significantly in goat skins isolated from white and brown coat-colored skins. Methods: Expression patterns of circRNA18 in goat skin and melanocytes were determined by qRT-PCR and In situ hybridization. The circRNA18 interference vector was designed and synthesized to transfect melanocytes and detect the effect of circRNA18 interference on melanin production. Bioinformatics software was used to predict the targeted adsorption miRNAs of circRNA18, verified by luciferase assay. miRNA expression vector was constructed and transfected into melanocytes to detect the effect of miRNA on melanin production, and the targeted regulatory genes were detected by luciferase assay. Target gene interference vector was constructed to detect the influence of target gene interference on melanin production. Results: qRT-PCR results unveiled distinct expression patterns of circRNA18 in diverse tissues of male and female goats, while in situ hybridization assays showed that circRNA18 is expressed in the cytoplasm of melanocytes. Functional analysis demonstrated that the downregulation of circRNA18 in melanocytes leads to a significant increase (P<0.01) in melanin production. Bioinformatics analysis identified a potential miR-211 binding site on circRNA18, and luciferase assay confirmed their interaction. Overexpression of miR-211 in melanocytes significantly augmented (P<0.01) melanin production. There were two potential miR-211 binding sites on adenoviral E1A-binding protein (EP300), and the overexpression of miR-211 in melanocytes significantly decreased (P<0.001) EP300 expression, with luciferase assay confirming their interaction. Downregulation of EP300 expression in melanocytes through siRNA-EP300 transfection results in a substantial increase (P<0.05) in melanin production. qRT-PCR results indicated that overexpression of mimics-circRNA18 in melanocytes markedly suppressed (P<0.0001) miR-211 expression, significantly elevated (P<0.01) EP300 expression, and significantly inhibited (P<0.001) melanin production. Conclusion: circRNA18_46222157_46248185 acted as a negative regulator of melanogenesis in goat melanocytes by targeting the miR-211/EP300 pathway, and guiding animal hair color breeding strategies.

Deciphering the predictive value of senescence-related signature in lung adenocarcinoma: Implications for antitumor immunity and immunotherapy efficacy.

Objective: The senescence process is pivotal in both the onset and advancement of lung adenocarcinoma (LUAD), influencing cell growth, immune evasion, the potential for metastasis, and resistance to treatments. Senescent cells' dual nature, both harmful and advantageous, adds complexity to understanding their expression patterns and clinical relevance in LUAD. In this study, we sought to evaluate the predictive value of the senescence-related signature in survival outcomes and immunotherapy efficacy in patients with LUAD. Materials and methods: We integrated data from 1449 LUAD cases sourced from different publicly accessible datasets and a clinical cohort of Chinese LUAD patients. The Cox regression analysis employing the least absolute shrinkage and selection operator (LASSO) was performed on 156 senescence-associated genes to develop the senescence-related signature. Kaplan-Meier analysis and time-dependent receiver operating characteristic curves were utilizaed to assess the prognostic significance of the senescence-related signature. Functional annotation, immune infiltration analysis, and gene set variation analysis were applied to investigate the association of the senescence-related signature with anti-tumor immunity in LUAD. Immunotherapy cohorts of non-small cell lung cancer, urothelial carcinoma, skin cutaneous melanoma, and glioblastoma patients were included to assess the senescence-related signature in predicting immunotherapy efficacy. Results: The senescence-related signature, which encompasses seven senescence-related genes, namely, FOXM1, VDAC1, PPP3CA, MAPK13, PIK3CD, RRAS, and CCND3, was identified to have predictive significance across multiple LUAD cohorts and demonstrated a negative association with antitumor immunity and tumor-infiltrating neutrophils. Patients exhibiting low expression levels of the senescence-related signature responded more favorably to immune checkpoint inhibitors in various solid tumors, including LUAD. Inhibiting FOXM1 pharmacologically with thiostrepton produced tumor-suppressive effects and improved immunotherapy responses in a Lewis lung carcinoma mouse model. Conclusions: The senescence-related signature demonstrates potential in predicting patient prognosis and immunotherapy efficacy in LUAD.