Attentional Bias in Older Adults with Non-Clinical Depression: An Eye-Tracking Study.

BACKGROUND: Cognitive models of depression assert that attentional biases play an important role in the maintenance of depression. However, few studies have explored attentional bias in depressed older adults, and no consistent conclusions have been reached. METHODS: In the current study, we investigated attentional bias in older adults with non-clinical depression. Older adults aged over 60 with non-clinical depression and without depression were instructed to perform a free viewing task while their eye movements were tracked. RESULTS: The results showed that, compared to older adults without depression, non-clinically depressed older adults had longer total fixation durations and a greater number of fixations on sad stimuli. Moreover, non-depressed older adults exhibited a preference for pleasant images, whereas this effect was not observed in older adults with non-clinical depression. CONCLUSION: This study suggested that non-clinically depressed older adults have attentional bias, which is manifested as increased attention to sad stimuli and decreased attention to pleasant stimuli.The current study has functional and potential functional implications.

Integrated serum proteomic and N-glycoproteomic characterization of dengue patients.

Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.

Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been reported as a novel predictor for atherosclerosis and cardiovascular outcomes. This study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion (CTO) patients. METHODS: A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up period. Patients were divided into tertiles according to their baseline NLR levels at admission: low (n = 223), intermediate (n = 223), and high (n = 224). The incidence of major adverse cardiac events (MACEs) during the follow-up period, including all-cause death, nonfatal myocardial infarction (MI), or ischemia-driven revascularization, were compared among the three groups. RESULTS: Major adverse cardiac events were observed in 27 patients (12.1%) in the low tertile, 40 (17.9%) in the intermediate tertile, and 61 (27.2%) in the high NLR tertile (P < 0.001). Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE, ischemia-driven coronary revascularization, non-fatal MI, and mortality in patients within the high tertile than those in the low and intermediate groups (all P < 0.001). Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE (hazard ratio [HR] = 2.21; 95% confidence interval [CI]: 1.21-4.03; P = 0.009), ischemia-driven coronary revascularization (HR = 3.19; 95% CI: 1.56-6.52; P = 0.001), MI (HR = 2.61; 95% CI: 1.35-5.03; P = 0.043) and mortality (HR = 3.78; 95% CI: 1.65-8.77; P = 0.001). CONCLUSION: Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently predict cardiovascular risk in patients with CTO.

A combination of risk stratification systems for thyroid nodules and cervical lymph nodes may improve the diagnosis and management of thyroid nodules.

Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.

Visible-light promoted radical cascade cyclization of 3-allyl-2-arylquinazolinones for the synthesis of phosphorylated dihydroisoquinolino[1,2-b]quinazolinones.

A novel visible-light promoted metal-free radical cascade cyclization reaction has been developed with 3-allyl-2-arylquinazolinones as a new class of radical acceptor. This photocatalytic protocol represents an efficient approach to construct phosphorylated dihydroisoquinolino[1,2-b]quinazolinones featuring mild conditions, broad substrate scope, and gram-scale synthesis.

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.

Multiple factors trigger the formation and resuscitation of the VBNC state in alcohol-producing Klebsiella pneumoniae.

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Benzo[a]pyrene exposure disrupts the organelle distribution and function of mouse oocytes.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

An axonemal intron splicing program sustains Plasmodium male development.

Differentiation of male gametocytes into flagellated fertile male gametes relies on the assembly of axoneme, a major component of male development for mosquito transmission of the malaria parasite. RNA-binding protein (RBP)-mediated post-transcriptional regulation of mRNA plays important roles in eukaryotic sexual development, including the development of female Plasmodium. However, the role of RBP in defining the Plasmodium male transcriptome and its function in male gametogenesis remains incompletely understood. Here, we performed genome-wide screening for gender-specific RBPs and identified an undescribed male-specific RBP gene Rbpm1 in the Plasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with the spliceosome E complex and regulates the splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal protein expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. The splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcriptional regulation essential for Plasmodium male development.

The dynamic molecular characteristics of neutrophils are associated with disease progression in dengue patients.

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly during the defervescence phase (65.79%) in clinical cohorts. Bioinformatics analyses corroborated a significant reduction in neutrophil immune infiltration in dengue patients. Receiver operating characteristic curve analysis demonstrated that dynamic changes in neutrophil infiltration levels could predict disease progression, especially during the defervescence phase, with the area under the curve of 0.96. Three neutrophil-associated biomarkers-DHRS12, Transforming growth factor alpha, and ZDHHC19-were identified as promising for diagnosing and predicting dengue progression. In addition, the activation of neutrophil extracellular traps was significantly enhanced and linked to FcγR-mediated signaling pathways and Toll-like receptor signaling pathways. Neutrophil activation and depletion play a critical role in dengue's immune response. The identified biomarkers and their associated pathways offer potential for improved diagnosis and understanding of dengue pathogenesis and progression.

Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Update on kidney injury caused by multiple myeloma.

Multiple myeloma (MM) is a form of clonal plasma cell malignancy that associates with clinical manifestations such as anemia, hypercalcemia, bone pain, and renal impairment. Approximately 20-50% of MM patients at initial diagnosis experience renal injury, a vital complication that significantly influences prognosis and quality of life. This review seeks to clarify the multifaceted mechanisms of renal injury in MM, scrutinizing the pathogenic role of monoclonal proteins, the impact of hypercalcemia, and direct renal infiltration by plasma cells. Furthermore, it evaluates current diagnostic approaches, reviews management strategies, and highlights potential avenues for future research. By incorporating the latest scientific evidence and insights, this article aims to provide a comprehensive understanding of MM-associated renal impairment, offering a valuable resource for researchers and clinicians in handling this complex complication.

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

Identification and Characterization of Three Novel Solemo-like Viruses in the White-Backed Planthopper, Sogatella furcifera.

Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; Sogatella furcifera, Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family Solemoviridae and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.

Clinical features and viral load variations of Mpox: a retrospective study in Chongqing, China.

PURPOSE: Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. METHOD: We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. RESULTS: As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. CONCLUSION: In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Efficient Biodegradation of the Neonicotinoid Insecticide Flonicamid by Pseudaminobacter salicylatoxidans CGMCC 1.17248: Kinetics, Pathways, and Enzyme Properties.

Nitrile-containing insecticides can be converted into their amide derivatives by Pseudaminobacter salicylatoxidans. N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) is converted to 4-(trifluoromethyl) nicotinoyl glycine (TFNG) using nitrile hydratase/amidase. However, the amidase that catalyzes this bioconversion has not yet been fully elucidated. In this study, it was discovered that flonicamid (FLO) is degraded by P. salicylatoxidans into the acid metabolite TFNG via the intermediate TFNG-AM. A half-life of 18.7 h was observed for P. salicylatoxidans resting cells, which transformed 82.8% of the available FLO in 48 h. The resulting amide metabolite, TFNG-AM, was almost all converted to TFNG within 19 d. A novel amidase-encoding gene was cloned and overexpressed in Escherichia coli. The enzyme, PmsiA, hydrolyzed TFNG-AM to TFNG. Despite being categorized as a member of the amidase signature enzyme superfamily, PsmiA only shares 20-30% identity with the 14 previously identified members of this family, indicating that PsmiA represents a novel class of enzyme. Homology structural modeling and molecular docking analyses suggested that key residues Glu247 and Met242 may significantly impact the catalytic activity of PsmiA. This study contributes to our understanding of the biodegradation process of nitrile-containing insecticides and the relationship between the structure and function of metabolic enzymes.

The placental blood perfusion and LINC00473-mediated promotion of trophoblast apoptosis in fetal growth restriction.

This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VIMV), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VIMV, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.

Unveiling shared biomarkers and therapeutic targets between systemic lupus erythematosus and heart failure through bioinformatics analysis.

Background: Systemic lupus erythematosus (SLE) is frequently accompanied by various complications, with cardiovascular diseases being particularly concerning due to their high mortality rate. Although there is clinical evidence suggesting a potential correlation between SLE and heart failure (HF), the underlying shared mechanism is not fully understood. Therefore, it is imperative to explore the potential mechanisms and shared therapeutic targets between SLE and HF. Methods: The SLE and HF datasets were downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) in both SLE and HF were performed using "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) analyses were conducted to analyze the enriched functions and pathways of DEGs in both SLE and HF datasets. Protein-Protein Interaction network (PPI) and the molecular complex detection (MCODE) plugins in the Cytoscape software were performed to identify the shared hub genes between SLE and HF datasets. R package "limma" was utilized to validate the expression of hub genes based on SLE (GSE122459) and HF (GSE196656) datasets. CIBERSORT algorithm was utilized to analyze the immune cell infiltration of SLE and HF samples based on SLE (GSE112087) and HF (GSE116250) datasets. A weighted gene co-expression network analysis (WGCNA) network was established to further validate the hub genes based on HF dataset (GSE116250). Molecular biology techniques were conducted to validate the hub genes. Results: 999 shared DGEs were identified between SLE and HF datasets, which were mainly enriched in pathways related to Th17 cell differentiation. 5 shared hub genes among the common DGEs between SLE and HF datasets were screened and validated, including HSP90AB1, NEDD8, RPLP0, UBB, and UBC. Additionally, 5 hub genes were identified in the central part of the MEbrown module, showing the strongest correlation with dilated cardiomyopathy. HSP90AB1 and UBC were upregulated in failing hearts compared to non-failing hearts, while UBB, NEDD8, and RPLP0 did not show significant changes. Conclusion: HSP90AB1 and UBC are closely related to the co-pathogenesis of SLE and HF mediated by immune cell infiltration. They serve as promising molecular markers and potential therapeutic targets for the treatment of SLE combined with HF.