Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. RESULTS: In this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. CONCLUSION: Anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Posterior corneal stability after small incision lenticule extraction with different optical zones.

BACKGROUND: To assess the changes in the posterior corneal surface following small incision lenticule extraction (SMILE) with different optical zones. METHODS: In this retrospective study, 106 eyes of 106 patients who underwent SMILE were recruited 3 years after the procedure. Eyes were divided into two groups according to the size of the surgical optical zone: group A (52 eyes, ≤6.2 mm) and group B (54 eyes, ≥6.5 mm). Posterior central elevation (PCE) and 12 other points at 45°, 135°, 225° and 315° with distances of 1 mm, 2 mm and 3 mm from the centre were recorded from Pentacam. RESULTS: No iatrogenic keratectasia was identified, and eyes in the two groups showed comparable visual results. The overall trend in posterior corneal elevation changes was consistent for both groups. PCE decreased significantly from 1.33 ± 2.32 to 0.75 ± 2.41 in group A (P = 0.024) and from 0.87 ± 2.61 to 0.06 ± 2.74 in group B (P = 0.003). All points in the central 2 mm region in both groups were reduced postoperatively. In the 4 mm and 6 mm corneal annulus, almost all points at 225°and 315° showed backward displacement, with the most prominent change occurring at 315° in the 6 mm annulus (P < 0.001), indicating no forward protrusion in the inferior area. CONCLUSIONS: No forward protrusion in the posterior corneal surface was observed 3 years after SMILE with different optical zones. Comprehensive preoperative measurements are essential for ensuring corneal stability and avoiding iatrogenic keratectasia.

Copper-loaded Milk-Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction.

Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu2+ carrier through molecular-docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.

Metabolic and tolerance engineering of Komagataella phaffii for 2-phenylethanol production through genome-wide scanning.

BACKGROUND: 2-Phenylethanol (2-PE) is one of the most widely used spices. Recently, 2-PE has also been considered a potential aviation fuel booster. However, the lack of scientific understanding of the 2-PE biosynthetic pathway and the cellular response to 2-PE cytotoxicity are the most important obstacles to the efficient biosynthesis of 2-PE. RESULTS: Here, metabolic engineering and tolerance engineering strategies were used to improve the production of 2-PE in Komagataella phaffii. First, the endogenous genes encoding the amino acid permease GAP1, aminotransferase AAT2, phenylpyruvate decarboxylase KDC2, and aldehyde dehydrogenase ALD4 involved in the Ehrlich pathway and the 2-PE stress response gene NIT1 in K. phaffii were screened and characterized via comparative transcriptome analysis. Subsequently, metabolic engineering was employed to gradually reconstruct the 2-PE biosynthetic pathway, and the engineered strain S43 was obtained, which produced 2.98 g/L 2-PE in shake flask. Furthermore, transcriptional profiling analyses were utilized to screen for novel potential tolerance elements. Our results demonstrated that cells with knockout of the PDR12 and C4R2I5 genes exhibited a significant increase in 2-PE tolerance. To confirm the practical applications of these results, deletion of the PDR12 and C4R2I5 genes in the hyper 2-PE producing strain S43 dramatically increased the production of 2-PE by 18.12%, and the production was 3.54 g/L. CONCLUSION: This is the highest production of 2-PE produced by K. phaffii via L-phenylalanine conversion. These identified K. phaffii endogenous elements are highly conserved in other yeast species, suggesting that manipulation of these homologues might be a useful strategy for improving aromatic alcohol production. These results also enrich the understanding of aromatic compound biosynthetic pathways and 2-PE tolerance, and provide new elements and strategies for the synthesis of aromatic compounds by microbial cell factories.

Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins.

Plant communities may be co-invaded by invasive plants, sometimes even by congeneric invasive plants (CIPs). Despite the growing understanding of co-invasion in the environment, little is known about how CIP interactions and mechanisms regulate co-invasion. Darwin's naturalisation conundrum predicts that the coexistence of closely related species is difficult due to their structural and behavioural similarities. Nevertheless, communities containing closely related species are more susceptible to being invaded because close relatives may favour similar environments; therefore, this hypothesis should be followed in the co-invasion of CIPs. To explore whether the phylogenetic relatedness and origins of invasive species to CIPs can promote or hinder co-invasion, we conducted a controlled interaction and soil-legacy greenhouse experiment to quantify the growth response of invasive plants and their congeners. We consistently found that CIPs of identical origin were more likely to co-invade compared to CIPs of distinct origins. CIPs of distinct origins exhibited an antagonistic effect on co-invasion by allelopathy. Invasive plant-conditioned soil was more conducive to the growth of CIPs of identical origin than CIPs of distinct origins. Our results revealed the different effects of invader-invader phylogenetic relatedness on co-invader success and impact, suggesting the operation of different mechanisms across co-invasion.

Short-term inhalation of xenon during anesthesia for prevention of postoperative delirium in elderly patients undergoing laparoscopic radical colectomy: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. METHODS/DESIGN: This is a prospective, randomized, controlled trial and 132 patients aged 65-80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. DISCUSSION: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Dynamic decoding and dual synthetic data for automatic correction of grammar in low-resource scenario.

Grammar error correction systems are pivotal in the field of natural language processing (NLP), with a primary focus on identifying and correcting the grammatical integrity of written text. This is crucial for both language learning and formal communication. Recently, neural machine translation (NMT) has emerged as a promising approach in high demand. However, this approach faces significant challenges, particularly the scarcity of training data and the complexity of grammar error correction (GEC), especially for low-resource languages such as Indonesian. To address these challenges, we propose InSpelPoS, a confusion method that combines two synthetic data generation methods: the Inverted Spellchecker and Patterns+POS. Furthermore, we introduce an adapted seq2seq framework equipped with a dynamic decoding method and state-of-the-art Transformer-based neural language models to enhance the accuracy and efficiency of GEC. The dynamic decoding method is capable of navigating the complexities of GEC and correcting a wide range of errors, including contextual and grammatical errors. The proposed model leverages the contextual information of words and sentences to generate a corrected output. To assess the effectiveness of our proposed framework, we conducted experiments using synthetic data and compared its performance with existing GEC systems. The results demonstrate a significant improvement in the accuracy of Indonesian GEC compared to existing methods.

A method for calculating vector forces at human-mattress interface during sleeping positions utilizing image registration.

The vector forces at the human-mattress interface are not only crucial for understanding the distribution of vertical and shear forces exerted on the human body during sleep but also serves as a significant input for biomechanical models of sleeping positions, whose accuracy determines the credibility of predicting musculoskeletal system loads. In this study, we introduce a novel method for calculating the interface vector forces. By recording indentations after supine and lateral positions using a vacuum mattress and 3D scanner, we utilize image registration techniques to align body pressure distribution with the mattress deformation scanning images, thereby calculating the vector force values for each unit area (36.25 mm × 36.25 mm). This method was validated through five participants attendance from two perspectives, revealing that (1) the mean summation of the vertical force components is 98.67% ± 7.21% body weight, exhibiting good consistency, and mean ratio of horizontal component force to body weight is 2.18% ± 1.77%. (2) the predicted muscle activity using the vector forces as input to the sleep position model aligns with the measured muscle activity (%MVC), with correlation coefficient over 0.7. The proposed method contributes to the vector force distribution understanding and the analysis of musculoskeletal loads during sleep, providing valuable insights for mattress design and evaluation.

The m6A reader SlYTH2 negatively regulates tomato fruit aroma by impeding the translation process.

N6-methyladenosine (m6A) is a fundamentally important RNA modification for gene regulation, whose function is achieved through m6A readers. However, whether and how m6A readers play regulatory roles during fruit ripening and quality formation remains unclear. Here, we characterized SlYTH2 as a tomato m6A reader protein and profiled the binding sites of SlYTH2 at the transcriptome-wide level. SlYTH2 undergoes liquid-liquid phase separation and promotes RNA-protein condensate formation. The target mRNAs of SlYTH2, namely m6A-modified SlHPL and SlCCD1B associated with volatile synthesis, are enriched in SlYTH2-induced condensates. Through polysome profiling assays and proteomic analysis, we demonstrate that knockout of SlYTH2 expedites the translation process of SlHPL and SlCCD1B, resulting in augmented production of aroma-associated volatiles. This aroma enrichment significantly increased consumer preferences for CRISPR-edited fruit over wild type. These findings shed light on the underlying mechanisms of m6A in plant RNA metabolism and provided a promising strategy to generate fruits that are more attractive to consumers.

Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

[Research Progress of Functional Materials for Conversion of Agricultural Biomass Wastes].

Excess agricultural biomass waste is increasing rapidly, leading to many environmental and governance issues. Therefore, increased attention has been paid to the recycling and value-added application of agricultural biomass waste. In recent years, the research of agricultural biomass waste utilization and derived functional materials has mainly included the following two aspects： ① the extraction of natural polymers and value-added applications and ② the direct preparation of new carbon-based materials, including adsorption, catalysis, energy storage electrode, and composite functional materials. The conversion of agricultural biomass waste into functional materials has been gradually realized and widely used. To enable industrial-scale production and the quality and safety of agricultural biomass waste derivatives and to develop highly feasible and cost-effective biomass waste conversion methods should be the focus of future studies.

The causal role between circulating immune cells and diabetic nephropathy: a bidirectional Mendelian randomization with mediating insights.

Diabetic nephropathy (DN) is a critical inflammatory condition linked to diabetes, affecting millions worldwide. This study employs Mendelian randomization (MR) to explore the causal relationship between immune cell signatures and DN, analyzing over 731 immune signatures and incorporating data from 1400 metabolites to investigate potential mediators. Despite no statistically significant influence of DN on immunophenotypes after FDR correction, some phenotypes with unadjusted low P-values warranted mention, including CD34 on Hematopoietic Stem Cell (Myeloid cell Panel), CD45 on CD33- HLA DR- (Myeloid cell Panel). Furthermore, three immunophenotypes were identified to have a significant impact on DN risk: CD16-CD56 on HLA DR+ NK (TBNK Panel), CD45 on HLA DR+ T cell (TBNK Panel), and CD33dim HLA DR+ CD11b+ AC (Myeloid cell Panel). Our findings underscore the critical role of immune cells in DN, highlighting potential mediators and offering new insights into its underlying mechanisms.

Pruned tea biomass plays a significant role in functional food production: A review on characterization and comprehensive utilization of abandon-plucked fresh tea leaves.

Tea is the second largest nonalcoholic beverage in the world due to its characteristic flavor and well-known functional properties in vitro and in vivo. Global tea production reaches 6.397 million tons in 2022 and continues to rise. Fresh tea leaves are mainly harvested in spring, whereas thousands of tons are discarded in summer and autumn. Herein, pruned tea biomass refers to abandon-plucked leaves being pruned in the non-plucking period, especially in summer and autumn. At present, no relevant concluding remarks have been made on this undervalued biomass. This review summarizes the seasonal differences of intrinsic metabolites and pays special attention to the most critical bioactive and flavor compounds, including polyphenols, theanine, and caffeine. Additionally, meaningful and profound methods to transform abandon-plucked fresh tea leaves into high-value products are reviewed. In summer and autumn, tea plants accumulate much more phenols than in spring, especially epigallocatechin gallate (galloyl catechin), anthocyanins (catechin derivatives), and proanthocyanidins (polymerized catechins). Vigorous carbon metabolism induced by high light intensity and temperature in summer and autumn also accumulates carbohydrates, such as soluble sugars and cellulose. The characteristics of abandon-plucked tea leaves make them not ideal raw materials for tea, but suitable for novel tea products like beverages and food ingredients using traditional or hybrid technologies such as enzymatic transformation, microbial fermentation, formula screening, and extraction, with the abundant polyphenols in summer and autumn tea serving as prominent flavor and bioactive contributors.

Immune checkpoint inhibitor-associated new-onset hypophysitis: a retrospective analysis using the FAERS.

BACKGROUND: Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored. METHODS: In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy. RESULTS: The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007]. CONCLUSIONS: ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment. AIM: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model. METHODS: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1ß, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice. RESULTS: Transforming growth factor (TGF)-ß1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1ß, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF. CONCLUSION: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

Occurrence of Fusarium Crown Rot Caused by Fusarium culmorum on Winter Wheat in Xinjiang Uygur Autonomous Region, China.

Wheat (Triticum aestivum L.) is the predominant grain crop and plays a pivotal role in grain production in Xinjiang Uygur Autonomous Region (XUAR), China. Its cultivated area constitutes approximately half of the total sown area of grain crops in XUAR, with 1.14 million hectares in 2021. Fusarium crown rot (FCR) of wheat, caused by Fusarium culmorum (W.G. Smith) Sacc., is one of the most devastating soil-borne diseases known to seriously reduce grain yield (Ma et al. 2024; Saad et al. 2023). In 2016, FCR of wheat, caused by F. culmorum, was firstly identified in Henan Province, China (Li et al. 2016). In June 2023, during the investigation of FCR of wheat in Aksu Prefecture, XUAR, FCR on winter wheat (cv. Xindong 20) was found (82.761349°E, 41.612202°N). The grain-filling period for winter wheat in early June coincided with a period of high temperatures and water demand in Aksu Prefecture. Approximately 8% of the Xindong 20 wheat plants exhibited symptoms of white heads and browning at the stem base, with the disease present in 82% of the wheat fields surveyed. To identify the pathogens, 20 samples of diseased stem basal tissue, each 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, followed by three rinses with sterile water. These samples were then plated onto potato dextrose agar (PDA) medium at 25°C for 5 days. A total of 17 isolates with consistent morphological characteristics were obtained using single-spore technique, with an isolation rate of 85%. The isolated strains exhibited rapid growth on PDA, producing fluffy, pale-yellow hyphae, and accumulating a pale-yellow to dark red pigment on the bottom of the medium. On carnation leaf agar (CLA), these strains formed orange colonies due to the aggregation of a large number of macroconidia. The macroconidia were short and thick, with three to four septa and rounded apical cell, averaging 31.94 to 40.96 × 5.62 to 6.71 µm (Magnification of ×400). Microconidia were not observed. These morphological characters were consistent with those of F. culmorum (Leslie and Summerell. 2006). Two isolates (D-9 and D-11) were selected for molecular identification. The EF-1α gene fragment was amplified using primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') as previously described by O'Donnell et al. (1998). The two 665 bp PCR products were sequenced and submitted to GenBank (GenBank Accession No: PP763247 and PP763248) with 99. 7% identity to the published F. culmorum sequences (e.g., OP985478, OP985477, MG195126, KX702638). The molecular identification was further confirmed by F. culmorum species-specific PCR primers FcOIF/FcOIR (Nicholson et al. 1998). The expected PCR products of 553 bp were produced only in F. culmorum. Strains D-9 and D-11 were used to conduct the pathogenicity experiment on 7-day-old winter wheat (cv. Xindong 20) using drip in the lower stem inoculation method with a 10-µl of 106 macroconidia ml-1 suspension, and the control 7-day-old winter wheat were treated with sterile water (Xu et al. 2017). The experiments were replicated five times in a greenhouse at temperatures ranging from 20℃ to 25℃. After 4 weeks, all inoculated wheat seedlings showed stem base browning or even death. No symptoms were observed on the control plants. The fungus was reisolated from all inoculated wheat plants by the method described above and identified by morphological and PCR amplification using F. culmorum species-specific primers FcOIF/FcOIR. No F. culmorum was isolated from the control wheat plants, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of F.culmorum causing FCR on winter wheat in XUAR, China. Considering wheat is the predominant grain crop and plays a pivotal role in grain production in China, necessary measures should be taken to prevent the spread of F. culmorum to other regions.

M3HOGAT: A Multi-View Multi-Modal Multi-Scale High-Order Graph Attention Network for Microbe-Disease Association Prediction.

Numerous scientific studies have found a link between diverse microorganisms in the human body and complex human diseases. Because traditional experimental approaches are time-consuming and expensive, using computational methods to identify microbes correlated with diseases is critical. In this paper, a new microbe-disease association prediction model is proposed that combines a multi-view multi-modal network and a multi-scale feature fusion mechanism, called M3HOGAT. Firstly, a microbe-disease association network and multiple similarity views are constructed based on multi-source information. Then, consider that neighbor information from disparate orders might be more adept at learning node representations. Consequently, the higher-order graph attention network (HOGAT) is devised to aggregate neighbor information from disparate orders to extract microbe and disease features from different networks and views. Given that the embedding features of microbe and disease from different views possess varying importance, a multi-scale feature fusion mechanism is employed to learn their interaction information, thereby generating the final feature of microbes and diseases. Finally, an inner product decoder is used to reconstruct the microbe-disease association matrix. Compared with five state-of-the-art methods on the HMDAD and Disbiome datasets, the results of 5-fold cross-validations show that M3HOGAT achieves the best performance. Furthermore, case studies on asthma and obesity confirm the effectiveness of M3HOGAT in identifying potential disease-related microbes.

Reasons and experience for patients with amyotrophic lateral sclerosis using traditional Chinese medicine: a CARE-TCM based mixed method study.

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue. MATERIALS AND METHODS: This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires' outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes. RESULTS: Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable. CONCLUSION: Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).

Association between Dietary Patterns and All-Cause Mortality in the Chinese Old: Analysis of the Chinese Longitudinal Healthy Longevity Survey Cohort.

Diet is one of the most important ways to intervene and promote the health of older adults and reduce all-cause mortality. This study aimed to investigate the association between dietary patterns and all-cause mortality in the Chinese old. This study involved 11,958 subjects aged 65-116 years in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. Dietary patterns were derived from principal component analysis (PCA) with varimax rotation. Four dietary patterns were derived: the 'milk-egg-sugar pattern', 'carnivorous pattern', 'healthy pattern', and 'northeastern pattern'. Cox proportional hazard models were built for males and females separately to estimate the relationship between different dietary patterns and all-cause mortality. After adjusting for all covariates, the milk-egg-sugar pattern played a reverse role in mortality risk in males and females in different quartiles. In the carnivorous pattern, only males in the fourth quartile were observed to have a significantly reduced mortality risk (HR = 0.84 (95% CI: 0.77-0.93)). Both genders benefited from the healthy pattern, which consistently lowered mortality risk across all quartiles (males: HR = 0.87 (95% CI: 0.84-0.89); females: HR = 0.95 (95% CI: 0.92-0.97)). The northeastern pattern also showed an inverse association with all-cause mortality in males (HR = 0.94 (95% CI: 0.92-0.97)) and females (HR = 0.96 (95% CI: 0.93-0.98)). This study showed the association between dietary patterns and all-cause mortality in the Chinese old, which is significant for further quantitative studies.

Association between total cholesterol and all-cause mortality in oldest old: a national longitudinal study.

Background: A common sense is that lower serum cholesterol levels are better. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over. Methods: We selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey(CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome was all-cause mortality. The univariate and multivariate Cox regression analyses were used to estimate risk levels of all-cause mortality. We stratified the participants into three groups (<3.40, 3.40-4.39, ≥4.39 mmol/L) based on the restricted cubic splines methods. The survival probability according to total cholesterol category was calculated using the Kaplan-Meier curves, and the log-rank test was performed to analyze differences between the groups. Results: During the follow-up of three years, 282 participants died, 497 survived and 124 lost to follow-up. There was significant relationship between the total cholesterol and lower risk of all-cause mortality in the multivariable Cox regression analysis (HR=0.88, 95% CI: 0.78-1.00). Based on the restricted cubic splines methods, the total cholesterol was converted from a continuous variable to a categorical variable. The populations were divided into three groups (<3.40, 3.40-4.39, ≥4.39 mmol/L) according to the total cholesterol categorized by cutoff values. Compared to the total cholesterol level of <3.40 mmol/L, populations in the total cholesterol level of 3.40-4.39 mmol/L (HR = 0.72, 95% CI: 0.53-0.97) and ≥4.39 mmol/L (HR = 0.71, 95% CI: 0.52-0.96) groups had lower all-cause mortality in multivariate Cox regression analysis and higher survival probability in survival analysis. When two groups were divided, similar results were found among the populations in the total cholesterol level of ≥3.40 mmol/L compared to the populations in the total cholesterol level of <3.40 mmol/L groups. Conclusion: In oldest old aged 85 and older, serum total cholesterol levels are inversely associated with all-cause mortality. This study suggested that total cholesterol should be maintained to acceptable levels (≥ 3.40 mmol/L) in oldest old to achieve longevity.