Evaluation of the effect of Torulaspora delbrueckii on important volatile compounds in navel orange original brandy using E-nose combined with HS-SPME-GC-MS.

Simultaneous inoculation of non-Saccharomyces cerevisiae during the alcoholic fermentation process has been found to be an effective strategy for enhancing wine flavor. This study aimed to investigate the effect of Torulaspora delbrueckii NCUF305.2 on the flavor of navel orange original brandy (NOOB) using E-nose combined with HS-SPME-GC-MS. The results showed a significant increase (p < 0.05) in the sensitivity of NOOB to W5C, W3C, W1S, and W3S sensors by mixed fermentation (MF). Esters in NOOB increased by 4.13%, while higher alcohols increased by 21.93% (p < 0.001), terpenes and others increased by 52.07% and 40.99% (p < 0.01), respectively. Notably, several important volatile compounds with relative odor activity values above 10 showed an increase. Sensory analysis revealed that a more pronounced citrus-like flavor and higher overall appearance scores were found in MF than in pure fermentation (PF). These findings offer valuable theoretical guidance for enhancing the quality of fruit brandies.

Construction and regulation of high active sites in montmorillonite composite catalyst for the removal of ofloxacin via persulfate activation.

In this study, ionic liquids (ILs) were used as organic modifiers by introducing montmorillonite nanolayers containing potential C and N active sites between the montmorillonite nanolayers. Organically modified montmorillonite (ILs-Mt-p) was further prepared by high-temperature pyrolysis under N2 and used for the removal of ofloxacin (OFL) by activated peroxymonosulfate (PMS). Combined with XPS and other characterization analyses, it was found that the catalyst materials prepared from different organic modifiers had similar surface functional groups and graphitized structures, but contained differences in the types and numbers of C and N active sites. The catalyst (3CPC-Mt-p) obtained after pyrolysis of montmorillonite modified with cetylpyridinium chloride (CPC) had optimal catalytic performance, in which graphitic C, graphitic N, and carbonyl group (C[bond, double bond]O) could synergistically promote the activation of PMS by electron transfer, and 77.3 % of OFL could be removed within 60 min. The effects of OFL concentration, initial pH, and anions on the effects of OFL removal by the 3CPC-Mt-p/PMS system were further investigated. Satisfactory degradation results were obtained over a wide pH range. Cl- promoted the system to degrade OFL, while the presence of SO42-, H2PO4- and HA showed some inhibition, but overall the 3CPC-Mt-p catalysts had a strong anti-interference ability, showing good application prospects. The quenching experiments and EPR tests showed that O2-- and 1O2 in the 3CPC-Mt-p/PMS system were the main reactive oxygen species for the degradation of OFL, and •OH was also involved in the reaction. This study provides ideas for the construction and modulation of active sites in mineral materials such as montmorillonite and broadens the application of montmorillonite composite catalysts in advanced oxidation processes for the treatment of antibiotic wastewater.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective treatment options, highlighting the need for developing new therapeutic interventions. Here, we assessed the response to pharmacologic inhibition of KRAS, the central oncogenic driver of PDAC. In a panel of PDAC cell lines, inhibition of KRASG12D with MRTX1133 yielded variable efficacy in suppressing cell growth and downstream gene expression programs in 2D cultures. On the basis of CRISPR-Cas9 loss-of-function screens, ITGB1 was identified as a target to enhance the therapeutic response to MRTX1133 by regulating mechanotransduction signaling and YAP/TAZ expression, which was confirmed by gene-specific knockdown and combinatorial drug synergy. Interestingly, MRTX1133 was considerably more efficacious in 3D cell cultures. Moreover, MRTX1133 elicited a pronounced cytostatic effect in vivo and controlled tumor growth in PDAC patient-derived xenografts. In syngeneic models, KRASG12D inhibition led to tumor regression that did not occur in immune-deficient hosts. Digital spatial profiling on tumor tissues indicated that MRTX1133-mediated KRAS inhibition enhanced IFNγ signaling and induced antigen presentation that modulated the tumor microenvironment. Further investigation of the immunologic response using single-cell sequencing and multispectral imaging revealed that tumor regression was associated with suppression of neutrophils and influx of effector CD8+ T cells. Together, these findings demonstrate that both tumor cell-intrinsic and -extrinsic events contribute to response to MRTX1133 and credential KRASG12D inhibition as a promising therapeutic strategy for a large percentage of patients with PDAC. SIGNIFICANCE: Pharmacologic inhibition of KRAS elicits varied responses in pancreatic cancer 2D cell lines, 3D organoid cultures, and xenografts, underscoring the importance of mechanotransduction and the tumor microenvironment in regulating therapeutic responses.

Evaluation of bevacizumab biosimilar on wound healing complications in patients with colorectal cancer undergoing endoscopic mucosal resection: A systematic review and meta-analysis in anorectal medicine.

Complications related to wound healing pose substantial obstacle in the management of colorectal cancer (CRC), specifically in the field of anorectal medicine. Biosimilars of bevacizumab have emerged as crucial therapeutic agents in the management of these complications. With the particular emphasis on effects of Bevacizumab Biosimilar Plus on wound healing among patients diagnosed with CRC, this review underscores the potential of this anorectal medication to improve patient outcomes and was aimed to assess the safety and efficacy of Bevacizumab Biosimilar Plus in relation to complications associated with wound healing in patients with CRC. The assessment centers on its therapeutic potential and safety profile within the domain of anorectal medicine. In accordance with the PRISMA guidelines, a comprehensive literature search was performed, resulting in the identification of 19 pertinent studies out of an initial 918. Priority was given to assessing the safety and adverse effects of Bevacizumab Biosimilar Plus in conjunction with its effectiveness in wound healing. The extracted data comprised the following: study design, patient demographics, comprehensive treatment regimens, wound healing-specific outcomes and adverse effects. The evaluation of study quality was conducted utilizing the instruments provided by the Cochrane Collaboration and the Newcastle-Ottawa Scale (NOS). Bevacizumab Biosimilar Plus demonstrates efficacy in the management of wound healing complications among patients with CRC, with a safety and efficacy profile similar to that of the original Bevacizumab, according to the analysis. Notably, several studies reported improved rates of wound healing in relation to the biosimilar. The safety profiles exhibited similarities to the anticipated anti-VEGF agent effects. In wound management, the biosimilar also demonstrated advantages in terms of prolonged efficacy. In addition, analyses of cost-effectiveness suggested that the use of biosimilars could result in cost reductions. Bevacizumab Biosimilar Plus exhibited potential as an anorectal medication for the effective management of wound healing complications in patients with CRC. This has substantial ramifications for improving the quality of patient care, encompassing the affordability and effectiveness of treatments.

Extraocular muscle enlargement and proptosis in carotid cavernous fistulas.

PURPOSE: To evaluate the prevalence and pattern of extraocular muscle enlargement and proptosis in patients with carotid cavernous fistulas (CCF). METHODS: We conducted a retrospective study on patients with digital subtraction angiography (DSA) confirmed CCFs with neuroimaging (computed tomography or magnetic resonance imaging) performed prior to the DSA. The maximum extraocular muscle diameters were recorded. Extraocular muscles were considered enlarged if they were greater than two standard deviations above the normal muscle diameters. Proptosis was defined as the distance between the interzygomatic line to the anterior globe of ≥2 mm compared to the contralateral orbit or ≥21 mm. RESULTS: Forty orbits from 20 patients were included. The mean age of participants was 65 ± 15 years and 13 (65%) were female. Thirteen (65%) fistulas were indirect and seven (35%) were direct. There was enlargement of at least one muscle in 11 (27.5%) orbits, and this was not correlated with the type of fistula (direct/indirect). The inferior rectus was most commonly enlarged in seven orbits (17.5%), followed by the medial rectus in five orbits (12.5%). Proptosis was found in 17 (43%) orbits and was more common ipsilateral to the fistula (58% ipsilateral group vs 19% contralateral group, p < .01). CONCLUSION: Extraocular muscle enlargement was observed in over one-fourth of CCFs. When enlarged, the inferior and medial rectus muscles are most commonly involved. These findings may help clinicians and radiologists when evaluating the CT or MRI scans of patients with suspected CCFs.

Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.

OBJECTIVES: To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. MATERIALS AND METHODS: The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. RESULTS: Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). CONCLUSION: T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. CLINICAL RELEVANCE STATEMENT: Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. KEY POINTS: • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.

Polystyrene nanobeads exacerbate chronic colitis in mice involving in oxidative stress and hepatic lipid metabolism.

BACKGROUND: Nanoplastics (NPs) are omnipresent in our lives as a new type of pollution with a tiny size. It can enter organisms from the environment, accumulate in the body, and be passed down the food chain. Inflammatory bowel disease (IBD) is a nonspecific intestinal inflammatory disease that is recurrent and prevalent in the population. Given that the intestinal features of colitis may affect the behavior and toxicity of NPs, it is imperative to clarify the risk and toxicity mechanisms of NPs in colitis models. METHODS AND RESULTS: In this study, mice were subjected to three cycles of 5-day dextran sulfate sodium (DSS) exposures, with a break of 7 to 11 days between each cycle. After the first cycle of DSS exposure, the mice were fed gavagely with water containing 100 nm polystyrene nanobeads (PS-NPs, at concentrations of 1 mg/kg·BW, 5 mg/kg·BW and 25 mg/kg·BW, respectively) for 28 consecutive days. The results demonstrated that cyclic administration of DSS induced chronic inflammation in mice, while the standard drug "5-aminosalicylic acid (5-ASA)" treatment partially improved colitis manifestations. PS-NPs exacerbated intestinal inflammation in mice with chronic colitis by activating the MAPK signaling pathway. Furthermore, PS-NPs aggravated inflammation, oxidative stress, as well as hepatic lipid metabolism disturbance in the liver of mice with chronic colitis. CONCLUSION: PS-NPs exacerbate intestinal inflammation and injury in mice with chronic colitis. This finding highlights chronically ill populations' susceptibility to environmental hazards, which urgent more research and risk assessment studies.

Selection on Visual Opsin Genes in Diurnal Neotropical Frogs and Loss of the SWS2 Opsin in Poison Frogs.

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here, we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae: Atelopus), and pumpkin toadlets (Brachycephalidae: Brachycephalus). We found evidence of positive selection on 44 amino acid sites in LWS, SWS1, SWS2, and RH1 opsin genes, of which one in LWS and two in RH1 have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence that SWS2, normally expressed in rod cells in frogs and some salamanders, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their behavior. Our analyses show that assessments of opsin diversification in across taxa could expand our understanding of the role of sensory system evolution in ecological adaptation.

Assessment of early anthracycline-induced cardiotoxicity using segmental strain of cardiac magnetic resonance compared with global strain and functional parameters: an animal study.

Background: The identification of anthracycline-induced cardiotoxicity holds significant importance in guiding subsequent treatment strategies, and recent research has demonstrated the efficacy of cardiac magnetic resonance (CMR) global strain analysis for its diagnosis. On the other hand, it is noteworthy that abnormal global myocardial strain may exhibit a temporal delay due to different cardiac movement in each segment of the left ventricle. To address this concern, this study aims to assess the diagnostic utility of CMR segmental strain analysis as an early detection method for cardiotoxicity. Methods: A serials of CMR scans were performed in 18 adult males New Zealand rabbits at baseline time (n=15), followed by scans at week 2 (n=15), week 4 (n=9), week 6 (n=6), and week 8 (n=5) after each week's anthracycline injection. Additionally, following each CMR scan, two to three rabbits were euthanized for pathological comparison. Cardiac functional parameters, global peak strain parameters, segmental peak strain parameters of the left ventricle, and the presence of myocardial cells damage were obtained. A mixed linear model was employed to obtain the earliest CMR diagnostic time. Receiver operating characteristic (ROC) analysis was performed to get the parameter threshold indicative of cardiotoxicity. Results: The left ventricular ejection fraction decreased at week 8 (P=0.002). There were no statistical differences in global strain throughout the experiment period (P>0.05). Regarding segmental strain analysis, the peak segmental radial strain of the apical lateral wall exhibited a decrease starting from week 2 and reached its lowest point at this week (P=0.011). Conversely, peak segmental circumferential strain of the apical anterior wall showed an increase at week 2 and reached its peak at week 6 (P=0.026). The cutoff strain value by ROC analysis for these two walls were 46.285 and -16.920, with the respective areas under the curve (AUC) 0.593 [specificity =0.267, sensitivity =1.000, 95% confidence interval (CI): 0.471-0.777] and 0.764 (specificity =0.733, sensitivity =0.784, 95% CI: 0.511-0.816). Peak segmental longitudinal strain of the apical anterior and apical lateral wall showed relatively delayed changes, occurring in the 4th week (P=0.030 and P=0.048), the cutoff values for these strains were -12.415 and -15.960, with corresponding AUCs of 0.645 (specificity =0.333, sensitivity =0.955, 95% CI: 0.495-0.795) and 0.717 (specificity =0.433, sensitivity =0.955, 95% CI: 0.566-0.902), respectively. Notably, the myocardial injury was also observed at the corresponding periods. Conclusions: Based on experimental evidence, the peak segmental strain of the apical lateral and anterior wall, as determined by CMR, demonstrated an earlier detection of anthracycline-induced cardiotoxicity compared to peak global strain and cardiac function.

Discrimination of Dioscorea species (Chinese yam) using FT-IR integrated with chemometric approach.

Dioscorea oppositifolia is an important crop and functional food. D. oppositifolia tuber is often adulterated with D. persimilis, D. alata, and D. fordii tuber in the commercial market. This study proposed an integrated Fourier transform infrared spectroscopy (FT-IR) with chemometric approach to differentiate these four Dioscorea species. A total of 107 Dioscorea spp. tuber samples were collected from different locations in China. Principal Component Analysis (PCA), PCA-Class, and Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) were utilised to classify the FT-IR spectra. In this PCA is unable to differentiate the Dioscorea spp. tuber effectively. However, PCA-Class and OPLS-DA can distinguish spp. these 4 species Dioscorea tuber with high accuracy, sensitivity, and specificity. Additionally, the RMSEE, RMSEP and RMSECV values for OPLS-DA model were low, showing that it is a good model. The combination of FT-IR with the PCA-Class and OPLS-DA is practical in discriminating Dioscorea spp. tubers.

Pharmacologically targeting KRAS G12D in PDAC models: tumor cell intrinsic and extrinsic impact.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which new therapeutic interventions are needed. Here we assessed the cellular response to pharmacological KRAS inhibition, which target the central oncogenic factor in PDAC. In a panel of PDAC cell lines, pharmaceutical inhibition of KRAS G12D allele, with MRTX1133 yields variable efficacy in the suppression of cell growth and downstream gene expression programs in 2D culture. CRISPR screens identify new drivers for enhanced therapeutic response that regulate focal adhesion and signaling cascades, which were confirmed by gene specific knockdowns and combinatorial drug synergy. Interestingly, MRTX1133 is considerably more efficacious in the context of 3D cell cultures and in vivo PDAC patient-derived xenografts. In syngeneic models, KRAS G12D inhibition elicits potent tumor regression that did not occur in immune-deficient hosts. Digital spatial profiling on tumor tissues indicates that MRTX1133 activates interferon-γ signaling and induces antigen presentation that modulate the tumor microenvironment. Further investigation on the immunological response using single cell sequencing and multispectral imaging reveals that tumor regression is associated with suppression of neutrophils and influx of effector CD8 + T-cells. Thus, both tumor cell intrinsic and extrinsic events contribute to response and credential KRAS G12D inhibition as promising strategy for a large percentage of PDAC tumors.

Case report: Coronavirus Disease 2019 (COVID-19) modified RNA vaccination-induced Adult-Onset Still's Disease with fulminant myocarditis as initial presentation.

Myocarditis is a rare complication of Coronavirus Disease 2019 (COVID-19) vaccination. We report a case of an elderly female who presented initially with acute myocarditis, fulminant heart failure, and atrial fibrillation after receiving a modified ribonucleic acid (mRNA) vaccine (BNT162b2). Unlike other patients with vaccine-induced myocarditis, she developed persistent fever, sore throat, polyarthralgia, diffuse macular rash, and lymphadenopathy. After extensive investigation, she was diagnosed with post-vaccination Adult-Onset Still's Disease. The systemic inflammation gradually subsided after the use of non-steroidal anti-inflammatory drugs and systemic steroids. She was discharged from hospital with stable hemodynamics. Methotrexate was subsequently given to maintain long-term remission.

Evaluating the Ability of Open-Source Artificial Intelligence to Predict Accepting-Journal Impact Factor and Eigenfactor Score Using Academic Article Abstracts: Cross-sectional Machine Learning Analysis.

BACKGROUND: Strategies to improve the selection of appropriate target journals may reduce delays in disseminating research results. Machine learning is increasingly used in content-based recommender algorithms to guide journal submissions for academic articles. OBJECTIVE: We sought to evaluate the performance of open-source artificial intelligence to predict the impact factor or Eigenfactor score tertile using academic article abstracts. METHODS: PubMed-indexed articles published between 2016 and 2021 were identified with the Medical Subject Headings (MeSH) terms "ophthalmology," "radiology," and "neurology." Journals, titles, abstracts, author lists, and MeSH terms were collected. Journal impact factor and Eigenfactor scores were sourced from the 2020 Clarivate Journal Citation Report. The journals included in the study were allocated percentile ranks based on impact factor and Eigenfactor scores, compared with other journals that released publications in the same year. All abstracts were preprocessed, which included the removal of the abstract structure, and combined with titles, authors, and MeSH terms as a single input. The input data underwent preprocessing with the inbuilt ktrain Bidirectional Encoder Representations from Transformers (BERT) preprocessing library before analysis with BERT. Before use for logistic regression and XGBoost models, the input data underwent punctuation removal, negation detection, stemming, and conversion into a term frequency-inverse document frequency array. Following this preprocessing, data were randomly split into training and testing data sets with a 3:1 train:test ratio. Models were developed to predict whether a given article would be published in a first, second, or third tertile journal (0-33rd centile, 34th-66th centile, or 67th-100th centile), as ranked either by impact factor or Eigenfactor score. BERT, XGBoost, and logistic regression models were developed on the training data set before evaluation on the hold-out test data set. The primary outcome was overall classification accuracy for the best-performing model in the prediction of accepting journal impact factor tertile. RESULTS: There were 10,813 articles from 382 unique journals. The median impact factor and Eigenfactor score were 2.117 (IQR 1.102-2.622) and 0.00247 (IQR 0.00105-0.03), respectively. The BERT model achieved the highest impact factor tertile classification accuracy of 75.0%, followed by an accuracy of 71.6% for XGBoost and 65.4% for logistic regression. Similarly, BERT achieved the highest Eigenfactor score tertile classification accuracy of 73.6%, followed by an accuracy of 71.8% for XGBoost and 65.3% for logistic regression. CONCLUSIONS: Open-source artificial intelligence can predict the impact factor and Eigenfactor score of accepting peer-reviewed journals. Further studies are required to examine the effect on publication success and the time-to-publication of such recommender systems.

Angioimmunoblastic T-Cell Lymphoma Diagnosed From Serous Effusion by Integration of Cytologic Features and Ancillary Studies.

OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Treatment-resistant depression and risk of autoimmune diseases: evidence from a population-based cohort and nested case-control study.

Recent literature indicates that patients with depression had increased immune activation. We hypothesised that treatment-resistant depression (TRD), an indicator of non-responsive depression with long-term dysregulated inflammation, could be an independent risk factor for subsequent autoimmune diseases. We performed a cohort study and a nested case-control study to examine the association between TRD and risk of autoimmune diseases, and to explore potential sex-specific difference. Using electronic medical records in Hong Kong, we identified 24,576 patients with incident depression between 2014 and 2016 without autoimmune history and followed up from diagnosis to death or December 2020 to identify TRD status and autoimmune incidence. TRD was defined as having at least two antidepressant regimens and the third regimen to confirm previous treatment failures. Based on age, sex and year of depression, we matched TRD patients 1:4 to the non-TRD in the cohort analysis using nearest-neighbour matching, and matched cases and controls 1:10 using incidence density sampling in the nested case-control analysis. We conducted survival analyses and conditional logistic regression respectively for risk estimation, adjusting for medical history. Across the study period, 4349 patients without autoimmune history (17.7%) developed TRD. With 71,163 person-years of follow-up, the cumulative incidence of 22 types of autoimmune diseases among the TRD patients was generally higher than the non-TRD (21.5 vs. 14.4 per 10,000 person-years). Cox model suggested a non-significant association (HR:1.48, 95% CI: 0.99-2.24, p = 0.059), whereas conditional logistic model showed a significant association (OR: 1.67, 95% CI: 1.10-2.53, p = 0.017) between TRD status and autoimmune diseases. Subgroup analysis showed that the association was significant in organ-specific diseases but not in systemic diseases. Risk magnitudes were generally higher among men compared to women. In conclusion, our findings provide evidence for an increased risk of autoimmune diseases in patients with TRD. Controlling chronic inflammation in hard-to-treat depression might play a role in preventing subsequent autoimmunity.

Study on the Hierarchical Predictive Control of Semiconductor Silicon Single Crystal Quality Based on the Soft Sensor Model.

Silicon single crystal (SSC) quality monitoring and control has been a hot research topic in the field of the Czochralski crystal growth process. Considering that the traditional SSC control method ignores the crystal quality factor, this paper proposes a hierarchical predictive control strategy based on a soft sensor model for online control of SSC diameter and crystal quality. First, the proposed control strategy considers the V/G variable (V is the crystal pulling rate, and G is the axial temperature gradient at the solid-liquid interface), a factor related to crystal quality. Aiming at the problem that the V/G variable is difficult to measure directly, a soft sensor model based on SAE-RF is established to realize the online monitoring of the V/G variable and then complete hierarchical prediction control of SSC quality. Second, in the hierarchical control process, PID control of the inner layer is used to quickly stabilize the system. Model predictive control (MPC) of the outer layer is used to handle system constraints and enhance the control performance of the inner layer. In addition, the SAE-RF-based soft sensor model is used to monitor the crystal quality V/G variable online, thereby ensuring that the output of the controlled system meets the desired crystal diameter and V/G requirements. Finally, based on the industrial data of the actual Czochralski SSC growth process, the effectiveness of the proposed crystal quality hierarchical predictive control method is verified.

Arabidopsis mRNA decay landscape shaped by XRN 5'-3' exoribonucleases.

5'-3' exoribonucleases (XRNs) play crucial roles in the control of RNA processing, quality, and quantity in eukaryotes. Although genome-wide profiling of RNA decay fragments is now feasible, how XRNs shape the plant mRNA degradome remains elusive. Here, we profiled and analyzed the RNA degradomes of Arabidopsis wild-type and mutant plants with defects in XRN activity. Deficiency of nuclear XRN3 or cytoplasmic XRN4 activity but not nuclear XRN2 activity greatly altered Arabidopsis mRNA decay profiles. Short excised linear introns and cleaved pre-mRNA fragments downstream of polyadenylation sites were polyadenylated and stabilized in the xrn3 mutant, demonstrating the unique function of XRN3 in the removal of cleavage remnants from pre-mRNA processing. Further analysis of stabilized XRN3 substrates confirmed that pre-mRNA 3' end cleavage frequently occurs after adenosine. The most abundant decay intermediates in wild-type plants include not only the primary substrates of XRN4 but also the products of XRN4-mediated cytoplasmic decay. An increase in decay intermediates with 5' ends upstream of a consensus motif in the xrn4 mutant suggests that there is an endonucleolytic cleavage mechanism targeting the 3' untranslated regions of many Arabidopsis mRNAs. However, analysis of decay fragments in the xrn4 mutant indicated that, except for microRNA-directed slicing, endonucleolytic cleavage events in the coding sequence rarely result in major decay intermediates. Together, these findings reveal the major substrates and products of nuclear and cytoplasmic XRNs along Arabidopsis transcripts and provide a basis for precise interpretation of RNA degradome data.

High-throughput phenotyping of infection by diverse microsporidia species reveals a wild C. elegans strain with opposing resistance and susceptibility traits.

Animals are under constant selective pressure from a myriad of diverse pathogens. Microsporidia are ubiquitous animal parasites, but the influence they exert on shaping animal genomes is mostly unknown. Using multiplexed competition assays, we measured the impact of four different species of microsporidia on 22 wild isolates of Caenorhabditis elegans. This resulted in the identification and confirmation of 13 strains with significantly altered population fitness profiles under infection conditions. One of these identified strains, JU1400, is sensitive to an epidermal-infecting species by lacking tolerance to infection. JU1400 is also resistant to an intestinal-infecting species and can specifically recognize and destroy this pathogen. Genetic mapping of JU1400 demonstrates that these two opposing phenotypes are caused by separate loci. Transcriptional analysis reveals the JU1400 sensitivity to epidermal microsporidia infection results in a response pattern that shares similarity to toxin-induced responses. In contrast, we do not observe JU1400 intestinal resistance being regulated at the transcriptional level. The transcriptional response to these four microsporidia species is conserved, with C. elegans strain-specific differences in potential immune genes. Together, our results show that phenotypic differences to microsporidia infection amongst C. elegans are common and that animals can evolve species-specific genetic interactions.