Sialylation status in placentas from anti-Ro/SSA- and anti-La/SSB-positive pregnant women.

Women affected by different autoimmune diseases and displaying positivity for anti-Ro/SSA and anti-La/SSB autoantibodies are at high risk of adverse pregnancies in which placental dysfunction seems to play a determinant role. Sialylation is known to have important implications in the maintenance of the normal morpho-functional features of the placenta. Hence, the present study aimed to investigate possible changes in the distribution and content of sialic acids (Sias) with different glycosidic linkages (i.e., α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias, and polysialic acid) in placentas from anti-Ro/SSA- and anti-La/SSB-positive pregnant women with autoimmune diseases by using lectin histochemistry and polysialic acid immunohistochemistry. Our findings revealed lower levels of α2,3-linked Sias in the trophoblast and basement membrane and/or basal plasma membrane of the pathological cases respect to control placentas. Some vessels of the pathological cases displayed α2,3-linked Sias. α2,6-linked Sias positivity was detected in the trophoblast and in some vessels of the pathological cases, while in control samples it was present only in the vessels. Lower levels of polysialic acid were observed in the trophoblast of pathological cases compared to controls. Collectively, our findings suggest that multiple changes in the sialylation status of placenta might affect placental morpho-functional features in anti-Ro/SSA- and anti-La/SSB-positive pregnancies.

Seamless knockins in Drosophila via CRISPR-triggered single-strand annealing.

CRISPR-Cas greatly facilitated the integration of exogenous sequences into specific loci. However, knockin generation in multicellular animals remains challenging, partially due to the complexity of insertion screening. Here, we describe SEED/Harvest, a method to generate knockins in Drosophila, based on CRISPR-Cas and the single-strand annealing (SSA) repair pathway. In SEED (from "scarless editing by element deletion"), a switchable cassette is first integrated into the target locus. In a subsequent CRISPR-triggered repair event, resolved by SSA, the cassette is seamlessly removed. Germline excision of SEED cassettes allows for fast and robust knockin generation of both fluorescent proteins and short protein tags in tandem. Tissue-specific expression of Cas9 results in somatic cassette excision, conferring spatiotemporal control of protein labeling and the conditional rescue of mutants. Finally, to achieve conditional protein labeling and manipulation of short tag knockins, we developed a genetic toolbox by functionalizing the ALFA nanobody.

Gestational Diabetes Mellitus Risk Factors in Pregnant Women Attending Public Health Institutions in Ethiopia's Sidama Region: An Unmatched Case-Control Study.

Background: Gestational diabetes mellitus (GDM), a chronic condition leading to glucose intolerance during pregnancy, is common in low- and middle-income countries, posing health risks to both the mother and fetus. Limited studies have been done in Ethiopia, especially using WHO's 2013 universal screening criteria. Therefore, this study aimed to evaluate the risk factors linked to GDM in women attending antenatal (ANC) clinics in Hawassa town public health institutions, located in the Sidama regional state of Ethiopia. Methods: An Unmatched case-control study was carried out in Ethiopia's Sidama Region from April 1st to June 10th, 2023, involving 510 pregnant women. The Oral Glucose Tolerance Test (OGTT) was utilized for universal screening and diagnosing GDM based on the updated 2013 WHO diagnostic criteria. Data analysis included descriptive and analytical statistics, with variables having p-values below 0.1 deemed suitable for bivariate analysis. Statistical significance was assessed using the adjusted odds ratio (AOR) with a 95% confidence interval and a p-value < 0.05. Results: The study involved 633 participants (255 cases and 378 controls), resulting in a 100% response rate, with women having an average age of 29.03 years.Variables such as: age at first conception (AOR=0.97, P=0.01, 95% CI (0.95,0.99)), urban residency (AOR=1.66, P<0.01, 95% CI(01.14,2.40)), widowed marital status (AOR=0.30, P=0.02, 95% CI (0.30,0.90)), parity (AOR=1.10, P<0.01, 95% CI (1.03,1.17)), history of stillbirth (AOR=1.15, P=0.03, 95% CI(1.04,2.30)), and previous cesarean section (AOR=1.86, P=0.01, 95% CI (1.13,2.66)) were identified as independent factors associated with GDM. Conclusion: The study concluded that factors like age at first conception, place of residence, marital status, parity, history of Caesarian section, and stillbirth were independently associated with GDM. Surprisingly, upper arm circumference (MUAC), a proxy for pre-gestational BMI, was not identified as a risk factor for GDM. It is recommended that healthcare providers conduct comprehensive GDM risk assessments in pregnant women to identify and address risk factors, and propose specific screening and intervention strategies.

Psychosocial interventions for depression among young people in Sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Depression among young people is a global health problem due to its rising prevalence and negative physical and social outcomes. The prevalence of depression and the treatment gap among young people in Sub-Saharan Africa (SSA) is higher than global estimates. Most psychosocial interventions for adolescent and youth depression were developed in high-income countries and less is known about their effectiveness in SSA. Due to contextual differences, findings from High-Income Countries (HICs) are less applicable to SSA. Yet, no systematic review of psychosocial interventions for depression among young people in SSA has been conducted. METHODS: A systematic literature search of four databases (Medline, Web of Science, PsycInfo, and Cochrane library) was conducted. Experimental studies published before May 2024 that evaluated the effect of psychosocial interventions on depressive symptoms among young people (aged 10-24 years) in SSA were included in the systematic review. Effect sizes (Hedge's g (g)) indicating differences between intervention and control groups were calculated using a random effects model. RESULTS: Twenty-two eligible studies were identified for the systematic review, of which eighteen randomized control trials (RCTs) involving 2338 participants were included in the meta-analysis. The findings revealed that psychosocial interventions significantly reduced depressive symptoms (g = -1.55, 95% CI -2.48, -0.63), although heterogeneity was high (I2 = 98.8%). Subgroup analysis revealed that efficacy differed significantly by intervention type, with Cognitive Behavioural Therapy (9 studies) showing the strongest effect (g = -2.84, 95% CI -4.29; -1.38). While Wise Interventions (a form of positive psychology interventions; 2 studies) had a moderate effect (g = -0.46, 95% C.I -0.53, -0.39), Interpersonal Psychotherapy (2 studies; g = -0.08, 95% CI -1.05, 0.88) and Creative Psychological Interventions (3 studies; g = -0.29, 95% CI -1.38, 0.79) showed smaller, non-significant effects. Sensitivity analysis excluding studies at high risk of bias strengthened the effect size. Few studies assessed factors affecting intervention efficacy and showed mixed effects of age, gender, and adherence levels. CONCLUSION: Psychosocial interventions, particularly CBT, significantly reduced depressive symptoms among young people in SSA. However, it is crucial to acknowledge the high heterogeneity which likely stems from variations in study populations and intervention delivery modalities. This highlights the need for further research to identify the specific intervention components and delivery methods that work best for distinct subpopulations. Future research should also explore how long intervention effects are maintained and factors affecting efficacy.

Diagnosis and Management of Fetal Arrhythmias in the Current Era.

Diagnosis and management of fetal arrhythmias have changed over the past 40-50 years since propranolol was first used to treat fetal tachycardia in 1975 and when first attempts were made at in utero pacing for complete heart block in 1986. Ongoing clinical trials, including the FAST therapy trial for fetal tachycardia and the STOP-BLOQ trial for anti-Ro-mediated fetal heart block, are working to improve diagnosis and management of fetal arrhythmias for both mother and fetus. We are also learning more about how "silent arrhythmias", like long QT syndrome and other inherited channelopathies, may be identified by recognizing "subtle" abnormalities in fetal heart rate, and while echocardiography yet remains the primary tool for diagnosing fetal arrhythmias, research efforts continue to advance the clinical envelope for fetal electrocardiography and fetal magnetocardiography. Pharmacologic management of fetal arrhythmias remains one of the most successful achievements of fetal intervention. Patience, vigilance, and multidisciplinary collaboration are key to successful diagnosis and treatment.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.

Comparative assessment of differently randomized accelerated particle swarm optimization and squirrel search algorithms for selective harmonics elimination problem.

A random initialization of the search particles is a strong argument in favor of the deployment of nature-inspired metaheuristic algorithms when the knowledge of a good initial guess is lacked. This article analyses the impact of the type of randomization on the working of algorithms and the acquired solutions. In this study, five different types of randomizations are applied to the Accelerated Particle Swarm Optimization (APSO) and Squirrel Search Algorithm (SSA) during the initializations and proceedings of the search particles for selective harmonics elimination (SHE). The types of randomizations include exponential, normal, Rayleigh, uniform, and Weibull characteristics. The statistical analysis shows that the type of randomization does impact the working of optimization algorithms and the fittest value of the objective function.

Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study.

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

Only 9% of mothers have eight and more ANC visit in 14 sub-saharan African countries; evidence from the most recent DHS 2018-2023: a multilevel analysis.

BACKGROUND: The world health organization's global health observatory defines maternal mortality as annual number of female deaths, regardless of the period or location of the pregnancy, from any cause related to or caused by pregnancy or its management (aside from accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy and an estimated 287 000 women worldwide passed away from maternal causes between 2016 and 2020, that works out to be about 800 deaths per day or about one every two minutes. METHOD: The most recent 2018-2023 DHS data set of 14 SSA countries was used a total of 89,489 weighted mothers who gave at list one live birth 3 years preceding the survey were included, a multilevel analysis was conducted. In the bi-variable analysis variables with p-value ≤ 0.20 were included in the multivariable analysis, and in the multivariable analysis, variables with p-value less than ≤ 0.05 were considered to be significant factors associated with having eight and more ANC visits. RESULT: The magnitude of having eight and more ANC visits in 14 sub-Saharan African countries was 8.9% (95% CI: 8.76-9.13) ranging from 3.66% (95% CI: 3.54-3.79) in Gabon to 18.92% (95% CI: 18.67-19.17) in Nigeria. The multilevel analysis shows that maternal age (40-44, AOR;2.09, 95%CI: 1.75-2.53), maternal occupational status (AOR;1.14, 95%CI; 1.07-1.22), maternal educational level (secondary and above, AOR;1.26, 95%CI; 1.16-1.38), wealth status(AOR;1.65, 95%CI; 1.50-1.82), media exposure (AOR;1.20, 95%CI; 1.11-1.31), pregnancy intention (AOR;1.12, 95%CI; 1.05-1.20), ever had terminated pregnancy (AOR;1.16 95%CI; 1.07-1.25), timely initiation of first ANC visit (AOR;4.79, 95%CI; 4.49-5.10), empowerment on respondents health care (AOR;1.43, 95%CI; 1.30-1.56), urban place of residence (AOR;1.33, 95%CI; 1.22-1.44) were factors highly influencing the utilization of AN. On the other hand higher birth order (AOR;0.54, 95%CI; 0.53-0.66), not using contraceptive (AOR;0.80, 95%CI; 0.75-0.86) and survey year (AOR;0.47, 95%CI; 0.34-0.65) were factors negatively associated with having eight and more ANC visits. CONCLUSION: In the 14 SSA included in this study, there is low adherence to WHO guidelines of eight and more ANC visits. Being educated, having jobs, getting access to media being from rural residence and rich wealth group contribute to having eight and more ANC visits, so we highly recommend policy implementers to advocate this practices.

Association between anti-SSA autoantibodies and conduction disturbances in heart failure.

BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear. OBJECTIVE: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF. METHODS: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required.

Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity.

Proteostasis, the maintenance of cellular protein balance, is essential for cell viability and is highly conserved across all organisms. Newly synthesized proteins, or "clients," undergo sequential processing by Hsp40, Hsp70, and Hsp90 chaperones to achieve proper folding and functionality. Despite extensive characterization of post-translational modifications (PTMs) on Hsp70 and Hsp90, the modifications on Hsp40 remain less understood. This study aims to elucidate the role of lysine acetylation on the yeast Hsp40, Ydj1. By mutating acetylation sites on Ydj1's J-domain to either abolish or mimic constitutive acetylation, we observed that preventing acetylation had no noticeable phenotypic impact, whereas acetyl-mimic mutants exhibited various defects indicative of impaired Ydj1 function. Proteomic analysis revealed several Ydj1 interactions affected by J-domain acetylation, notably with proteins involved in translation. Further investigation uncovered a novel role for Ydj1 acetylation in stabilizing ribosomal subunits and ensuring translational fidelity. Our data suggest that acetylation may facilitate the transfer of Ydj1 between Ssa1 and Hsp82. Collectively, this work highlights the critical role of Ydj1 acetylation in proteostasis and translational fidelity.

Towards the development of cost-effective point-of-care diagnostic tools for poverty-related infectious diseases in sub-Saharan Africa.

In this review, we examine the current landscape of point-of-care testing (POCT) diagnostic tools designed for poverty-related infectious diseases (PRIDs) in sub-Saharan Africa (sSA) while delineating key avenues for future advancements. Our analysis encompasses both established and emerging diagnostic methods for PRIDs, addressing the persistent challenges in POCT tool development and deployment, such as cost, accessibility, and reliability. We emphasize recent advancements in POCT diagnostic tools as well as platforms poised to enhance diagnostic testing in sSA. Recognizing the urgency for affordable and widely accessible POCT diagnostic tools to detect PRIDs in sSA, we advocate for a multidisciplinary approach. This approach integrates current and emerging diagnostic methods, explicitly addressing challenges hindering point-of-care (POC) tool development. Furthermore, it recognizes the profound impact of misdiagnosis on public and global health, emphasizing the need for effective tools. To facilitate the successful development and implementation of POCT diagnostic tools in sSA, we propose strategies including the creation of multi-analyte detection POCT tools, the implementation of education and training programs, community engagement initiatives, fostering public-private collaborations, and the establishment of reliable supply chains. Through these concerted efforts, we aim to accelerate the development of POCT in the sSA region, ensuring its effectiveness and accessibility in addressing the diagnostic challenges associated with PRIDs.

A Case of Superficial Siderosis with Elevated Anti-Ro/SSA Antibody.

Superficial siderosis (SS) of the central nervous system is a rare disorder that is caused by chronic or recurrent hemorrhage in the subarachnoid space via a dural defect at the spinal level. The most common clinical features of SS include slow-progressive sensorineural deafness, cerebellar symptoms, and pyramidal tract signs. Considering that SS can present with broad clinical manifestations, for precise diagnosis, this disease must be understood. Anti-Ro/SSA antibodies are commonly detected in patients with Sjögren's syndrome and are utilized as markers for autoimmune diseases. In this report, we present a unique pathological condition in which SS coincided with a positive anti-Ro/SSA antibody test result. During the diagnosis of gait disturbance, an elevation in anti-Ro/SSA antibody was detected, and steroid pulse therapy was initiated as the initial treatment for autoimmune diseases. Head magnetic resonance imaging (MRI) revealed extensive hypointensity as a dark band that surrounded the intracranial basal structures and cerebellar hemispheres. Spinal MRI indicated ventral longitudinal intraspinal fluid collection extending from C7 to T5 as well as a defect in the ventral T2-3 dura mater. Intraoperative visualization revealed that the intradural venous plexus was the source of bleeding that caused the SS. To our knowledge, this report is the first to discuss the presence of anti-Ro/SSA antibodies in patients with SS. The role of anti-Ro/SSA antibodies in the pathophysiology of SS remains unclear; therefore, to confirm a possible association, further research and accumulation of cases are required.

The level of wasting and associated factors among children aged 6-59 months in sub-Saharan African countries: multilevel ordinal logistic regression analysis.

Background: Despite various interventions to combat child malnutrition in sub-Saharan Africa, wasting remains a critical public health concern for children aged 6-59 months. Wasting is a significant predictor of child survival and development, with a heightened risk of mortality among children. However, there is a lack of recent comprehensive data on the prevalence, severity level, and factors contributing to wasting in this age group. Objective: To identify the severity levels of wasting and its individual and community-level factors contributing to wasting among children aged 6-59 months in Sub-Saharan African countries. Methods: This research utilized Demographic and Health Survey data from 34 Sub-Saharan African countries, spanning the period from 2007 to 2022. The study included a weighted sample of 180,317 6-59-month-old children. We employed a multilevel proportional odds model to identify factors predicting the severity of wasting. Adjusted odds ratios and 95% confidence intervals were reported to demonstrate significant relationships (p < 0.05) in the final model. Results: In Sub-Saharan Africa, 7.09% of children aged 6-59 months experience wasting (95% CI: 6.97, 7.20%). Among these children, the prevalence of moderate wasting is 4.97% (95% CI: 4.90, 5.10%), while severe wasting affects 2.12% (95% CI: 2.0, 2.20%). Factors such as term/post-term babies, wealth, frequency of feeding, improved toilet facilities, water sources, employed and educated mothers, rural residence, high community maternal education, and community media exposure are strongly associated with a lower chance of experiencing severe form of wasting. Conversely, birth order, family size, breastfeeding, diarrhea, cough, and fever, high community poverty, female household heads, and all Sub-Saharan Africa regions are linked to higher levels of wasting. Conclusion: The study findings underscore the persistent challenge of wasting among Sub-Saharan Africa's children, with 7.09% affected, of which 4.97% experience moderate wasting and 2.12% severe wasting. The identified predictors of wasting highlight the complex interplay of socio-economic, environmental, and health-related determinants. To address this issue improve access to healthcare and nutrition services, enhance sanitation infrastructure, promote women's empowerment, and implement community-based education programs. Additionally, prioritize early detection through routine screening and strengthen health systems' capacity to provide timely interventions.

[A recombinant adeno-associated virus expressing secretory TGF-ß type â ¡ receptor inhibits triple-negative murine breast cancer 4T1 cell proliferation and lung metastasis in mice].

OBJECTIVE: To investigate the effects of an adeno-associated virus (AAV2) vector expressing secretory transforming growth factor-ß (TGF-ß) type Ⅱ receptor (sTßRⅡ) extracellular domain-IgG2a Fc fusion protein (sTßRⅡ-Fc) on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice. METHODS: The pAAV-sTßRⅡ-Fc vector expressing sTßRⅡ-Fc fusion protein constructed by molecular cloning, the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTßRⅡ virus, which was purified by density gradient centrifugation with iodixanol. Western blotting was used to examine the effects of AAV-sTßRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin, vimentin and p-Smad2/3 in 4T1 cell xenografts in mice. BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTßRⅡ virus, AAV-GFP virus or PBS (n=6) through the tail vein, and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging. Ki67 expression in the tumor tissues and sTßRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining, and tumor metastases in the vital organs were examined with HE staining. RESULTS: The recombinant pAAV-sTßRⅡ-Fc vector successfully expressed sTßRⅡ in HEK 293T cells. Infection with AAV2-sTßRⅡ virus significantly reduced TGF-ß1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice (P<0.05). In the tumor-bearing mice, intravenous injection of AAV-sTßRⅡ virus significantly increased E-cadherin expression, reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues (P<0.05 or 0.01), and induced liver-specific sTßRⅡ expression without causing body weight loss or heart, liver, spleen or kidney pathologies. CONCLUSION: The recombinant AVV2 vector encoding sTßRⅡ extracellular domain is capable of blocking the TGF-ß signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

Prediction of total volatile basic nitrogen (TVB-N) in fish meal using a metal-oxide semiconductor electronic nose based on the VMD-SSA-LSTM algorithm.

BACKGROUND: The total volatile basic nitrogen (TVB-N) is the main indicator for evaluating the freshness of fish meal, and accurate detection and monitoring of TVB-N is of great significance for the health of animals and humans. Here, to realize fast and accurate identification of TVB-N, in this article, a self-developed electronic nose (e-nose) was used, and the mapping relationship between the gas sensor response characteristic information and TVB-N value was established to complete the freshness detection. RESULTS: The TVB-N variation curve was decomposed into seven subsequences with different frequency scales by means of variational mode decomposition (VMD). Each subsequence was modelled using different long short-term memory (LSTM) models, and finally, the final TVB-N prediction result was obtained by adding the prediction results based on different frequency components. To improve the performance of the LSTM, the sparrow search algorithm (SSA) was used to optimize the number of hidden units, learning rate and regularization coefficient of LSTM. The prediction results indicated that the high accuracy was obtained by the VMD-LSTM model optimized by SSA in predicting TVB-N. The coefficient of determination (R2), the root-mean-squared error (RMSE) and relative standard deviation (RSD) between the predicted value and the actual value of TVBN were 0.91, 0.115 and 6.39%, respectively. CONCLUSIONS: This method improves the performance of e-nose in detecting the freshness of fish meal and provides a reference for the quality detection of e-nose in other materials. © 2024 Society of Chemical Industry.

Thermotolerance in S. cerevisiae as a model to study extracellular vesicle biology.

The budding yeast Saccharomyces cerevisiae is a proven model organism for elucidating conserved eukaryotic biology, but to date its extracellular vesicle (EV) biology is understudied. Here, we show yeast transmit information through the extracellular medium that increases survival when confronted with heat stress and demonstrate the EV-enriched samples mediate this thermotolerance transfer. These samples contain vesicle-like particles that are exosome-sized and disrupting exosome biogenesis by targeting endosomal sorting complexes required for transport (ESCRT) machinery inhibits thermotolerance transfer. We find that Bro1, the yeast ortholog of the human exosome biomarker ALIX, is present in EV samples, and use Bro1 tagged with green fluorescent protein (GFP) to track EV release and uptake by endocytosis. Proteomics analysis reveals that heat shock protein 70 (HSP70) family proteins are enriched in EV samples that provide thermotolerance. We confirm the presence of the HSP70 ortholog stress-seventy subunit A2 (Ssa2) in EV samples and find that mutant yeast cells lacking SSA2 produce EVs but they fail to transfer thermotolerance. We conclude that Ssa2 within exosomes shared between yeast cells contributes to thermotolerance. Through this work, we advance Saccharomyces cerevisiae as an emerging model organism for elucidating molecular details of eukaryotic EV biology and establish a role for exosomes in heat stress and proteostasis that seems to be evolutionarily conserved.

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome.

Primary Sjögren's Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Association of Anti-Ro/SSA and Anti-La/SSB Autoantibodies With Pregnancy Outcome in the General Population.

Background: Autoimmune diseases encompass a diverse array of disorders that disturb the optimal functioning of the immune system, which is to eliminate the 'foreign or/and dangerous' to mistakenly target the body's own tissues. Objective: The aim of this research is to evaluate the most effective approach to managing autoimmune diseases within the framework of pregnancy. Methods: The exact causes and etiologies of these diseases are multifactorial and mostly still unclear. Ro/SSA autoantibodies and La/SSB, could be found in Sjögren's disease (SJ), systemic lupus (SLE) and other autoimmune disorders. Smoking, stress, UV exposure, vitamin D deficiency, and other genetic and environmental factors have been identified as risk factors for rheumatic diseases. Results: Over the years, an ever-increasing incidence of these diseases has been observed in the general population, with the female sex being at increased risk for their occurrence. This fact raises the question of what should be the management of these pathological entities during pregnancy. Taking into account the very significant impact on the quality of paitients'daily life and the seemingly augmented prevalence of autoimmune diseases, as well as their preference in the female population, the reasonable question arises as to what should be the optimal management of these diseases in the context of pregnancy. Conclusion: Given the limited data of the global medical community regarding the etiological factors and mechanisms that trigger the onset of rheumatic diseases, the management of pregnant women is a complex conundrum that health professionals are challenged to face and solve.

Helicopter Planet Gear Rim Crack Diagnosis and Trending Using Cepstrum Editing Enhanced with Deconvolution.

Detecting gear rim fatigue cracks using vibration signal analysis is often a challenging task, which typically requires a series of signal processing steps to detect and enhance fault features. This task becomes even harder in helicopter planetary gearboxes due to the complex interactions between different gear sets and the presence of vibration from sources other than the planetary gear set. In this paper, we propose an effectual processing algorithm to isolate and enhance rim crack features and to trend crack growth in planet gears. The algorithm is based on using cepstrum editing (or liftering) of the hunting-tooth synchronous averaged signals (angular domain) to extract harmonics and sidebands of the planet gears and low-pass filtering and minimum entropy deconvolution (MED) to enhance extracted fault features. The algorithm has been successfully applied to a vibration dataset collected from a planet gear rim crack propagation test undertaken in the Helicopter Transmission Test Facility (HTTF) at DSTG Melbourne. In this test, a seeded notch generated by an electric discharge machine (EDM) was used to initiate a fatigue crack that propagated through the gear rim body over 94 load cycles. The proposed algorithm demonstrated a successful isolation of incipient fault features and provided a reliable trending capability to monitor crack progression. Results of a comparative analysis showed that the proposed algorithm outperformed the traditional signal processing approach.