Search

Abstract Background L-DOPA has been considered the first-line therapy for treating Parkinson’s disease (PD) via restoring striatal dopamine (DA) to normalize the activity of local spiny projection neurons (SPNs) in the direct (dSPNs) pathway and the indirect (iSPNs) pathway. While the changes in striatal acetylcholine (ACh) induced by increasing DA have been extensively discussed, their validity remains controversial. Inhibition of striatal cholinergic signaling attenuates PD motor deficits. Interestingly, enhancing striatal ACh triggers local DA release, suggesting the pro-kinetic effects of ACh in movement control. Here, we investigated the in-vivo dynamics of ACh in the dorsolateral striatum (DLS) of the 6-OHDA-lesioned mouse model after L-DOPA administration, as well as its underlying mechanism, and to explore its modulatory role and mechanism in parkinsonian symptoms. Results Using in vivo fiber photometry recordings with genetically encoded fluorescent DA or ACh indicator, we found L-DOPA selectively decreased DLS ACh levels in parkinsonian conditions. DA inhibited ACh release via dopamine D2 receptors and dSPNs-mediated activation of type-A γ-aminobutyric acid receptors on cholinergic interneurons. Restoring DLS ACh levels during L-DOPA treatment induced additional DA release by activating nicotinic acetylcholine receptors, thereby promoting the activity of dSPNs and iSPNs. Enhancing DLS ACh facilitated L-DOPA-induced turning behavior but not dyskinesia in parkinsonian mice. Conclusions Our results demonstrated that enhancing striatal ACh facilitated the effect of L-DOPA by modulating DA tone. It may challenge the classical hypothesis of a purely competitive interaction between dopaminergic and cholinergic neuromodulation in improving PD motor deficits. Modulating ACh levels within the dopaminergic system may improve striatal DA availability in PD patients.

Objective Lower limb discrepancy (LLD) was frequently observed in patients with idiopathic scoliosis (IS), potentially associated with etiopathogenesis. Although sole lifts had been proposed as a conservative treatment for IS, evidence supporting their efficacy was limited. This study aimed to assess the effects of sole lift intervention on pediatric patients with mild IS, specifically focusing on thoracolumbar/lumbar (TL/L) curvature. Methods Twenty patients, with an average age of 12.3 ± 3.1 years and presenting mild TL/L curve (15.6° ± 6.2°), were selected from a pool of 267 pediatric IS patients in the outpatient of our spine center from February 2023 to August 2023. Inclusion criteria comprised a main TL/L curve ranging between 10° and 40°, the lower limb positioned at the convexity of the main curve, and LLD of less than 2 cm; individuals requiring bracing or surgical intervention were excluded. Custom sole lifts were used to address the shorter lower limb with the objective of leveling the pelvis. Radiographic evaluations were conducted both before and after intervention using standing full spine posteroanterior radiographs and full leg length radiographs. Statistical analysis was undertaken to evaluate curve correction and its associations with other influencing factors. Results The mean structural and functional LLD were 7.1 ± 4.5 mm and 7.1 ± 4.1 mm, respectively. Among the 20 patients, four exhibited structural LLD greater than 10 mm. The average follow‐up duration was 6.4 ± 1.9 months (range: 3–8 months). Following sole lift intervention (7.0 ± 3.0 mm), a significant reduction was observed in the TL/L curve compared to the pre‐sole lifting measurements (15.6° ± 6.2° vs. 12.1° ± 7.2°, p 0.05). Additionally, even after adjusting for other influencing factors, the TL/L Cobb angle remained significantly different between pre‐ and post‐sole lifting (p = 0.037). Conclusion This study confirmed the effectiveness of sole lift intervention in correcting TL/L and thoracic curves among the mild IS children with a main TL/L curve, providing a supplementary conservative treatment option for patients with the lower limb at the convexity of the main curve. Moreover, our findings underscored the active compensation of the lower limbs and the pelvis in the etiopathogenesis of IS, highlighting the importance of considering their influence in treatment strategies.

The genus Dendrostoma is known to inhabit tree barks associated with branch canker diseases in China and several countries of Europe. Previous studies indicated that species of Dendrostoma prefer inhabiting fagaceous hosts, especially species of Castanea. In the present study, we obtained four isolates from cankered branches of Chinese chestnut (C. mollissima) in Rizhao City, Shandong Province, China. Morphological comparisons and phylogenetical analyses of a combined ITS-tef1-rpb2 sequence matrix were conducted, which revealed two new species named Dendrostoma rizhaoense sp. nov. and D. tianii sp. nov. The new taxa are compared with other Dendrostoma species and comprehensive descriptions and illustrations are provided herein.

IntroductionThe poultry industry constantly seeks strategies to enhance broiler growth performance and overall health. Organic acidifiers, including L-lactic acid, L-malic acid, and acetic acid, have gained attention as potential feed additives to improve animal production by modulating gut health, enhancing nutrient absorption, and supporting immune function. Despite their promising effects in other animal species, the impact of this novel compound organic acidifier on broiler performance, metabolism, and immune response has not been fully elucidated. This study aims to evaluate the effects of this compound acidifier on growth performance, serum lipid profile, antioxidant status, and immune parameters in broilers, providing insights into its potential benefits as a dietary supplement for broiler health and productivity.MethodsA total of 240 broilers were randomly divided into four groups: a control group and three treatment groups receiving 0.25%, 0.5%, or 1.0% acidifier, with six replicates of ten birds each. Over a 6-week period, various parameters were measured, including serum triglycerides, high-density lipoproteins, lysozyme, immunoglobulins (IgA, IgM), superoxide dismutase (SOD) activity, IL-2, TNF-α, and gene expressions related to lipid metabolism.ResultsOver a 6-week period, the acidifier decreased serum triglycerides and high-density lipoproteins while also enhancing growth performance. Additionally, it raised the serum levels of lysozyme, IgA, IgM, and the SOD. Additionally, IL-2 and TNF-α concentrations in the jejunum mucosa decreased. The acidifier upregulated PPARα, AMPK, FABP1 and MTTP expressions, and downregulated APOB100. Overall, the acidifier effectively improved broiler growth performance during the early development phase primarily by enhancing hepatic lipid metabolism, antioxidant capacity, and immune function.ConclusionThese results suggest that the acidifier may accelerate liver lipid metabolism in broilers by modulating the gene expression profiles involved in lipid metabolism.

Light is an important factor for plant growth, and native plant communities are frequently invaded by alien plants to varying degrees. However, little is known about the effect of lighting on the resistance of native plant communities to alien plants with different degrees of invasion. We assessed the interactive effects of light condition and invasion degree on the growth of the invasive plant Solidago canadensis, the characteristics of the native plant communities and the invasion success of S. canadensis through both a field survey and greenhouse experiment. The field survey data showed that shading decreased the biomass of both S. canadensis and the native plant communities. However, it improved the relative dominance and thus, the invasion success of S. canadensis under the low and moderate invasion degrees but not at the high invasion degree. The data of the greenhouse experiment also showed that the native plant communities under shade were more susceptible to invasion by S. canadensis than the unshaded communities, particularly under the low and moderate invasion degree. In summary, we found that shading can weaken the resistance of native plant communities to alien plant invasions when there is a minimal invasion degree. These results underscore that managers need to be more attentive to the invasion of S. canadensis in sheltered environments. These findings provide a scientific reference to manage and control invasion by S. canadensis.

Background The relapse rate in myasthenia gravis (MG) is high, and promising therapies have emerged; however, identifying potential predictive factors for relapse remains a challenge. This study aimed to explore the association between circulating natural killer (NK) cell levels and the risk of recurrence in MG. Methods This retrospective cohort study included 265 patients with MG whose data were included in the Neurology Department of the Affiliated Hospital of Guizhou Medical University database between March 2015 and March 2022. Data from electronic medical records were collected, which included the patients’ circulating NK cell count (exposure variable) and demographic/clinical characteristics (covariates). The primary outcome was the 1-year MG recurrence rate. Results The study revealed a non-linear relationship between peripheral NK cell count and MG recurrence, with an inflection point at 5.38. Below this threshold, the risk of recurrence was low with higher NK cell counts (relative risk (RR): 0.23, 95% confidence interval (CI) [0.11–0.490]); above this threshold, no significant association was observed (RR: 1.43, 95% CI [0.62–3.34]). Furthermore, the NK cell proportion showed no significant linear or non-linear association with MG recurrence risk (RR: 0.84, 95% CI [0.57–1.2]). Conclusion This study provides epidemiological evidence of a potential association between peripheral NK cell count and MG recurrence risk, suggesting an immunoregulatory protective effect within a specific NK cell count range. These findings may inform more personalized MG treatment strategies, warranting further validation in larger and more diverse cohorts.

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

Background: Dyslipidemia has been implicated in autoimmunity; however, its association with myasthenia gravis (MG) prognosis is unclear. We aimed to investigate the correlation between baseline lipid profiles and risk of MG worsening. Methods: This 7-year retrospective cohort study conducted at a Chinese hospital included 264 adult patients with MG. Data on baseline lipids, 1-year worsening, and covariates, including demographics, MG characteristics, comorbidities, and treatments were extracted. Results: Univariate and multivariate logistic regression analyses failed to show a significant association between the risk of 1-year MG worsening and any of the seven blood lipid-related indicators. However, the subsequent non-linear analysis revealed an inflection point in the risk curve of ln[lipoprotein(a)], at 4.06 (58 nmol/L). The lipoprotein(a) levels on the left side of the inflection point presented a positive significant correlation with the risk of MG worsening (relative risk [RR]: 6.06, 95 % confidence interval [CI]: 1.00–38.57), whereas those on the right side of the inflection point demonstrated no significant correlation (RR: 0.86, 95 % CI: 0.55–1.34). Conclusions: Except for lipoprotein(a) levels being associated with worsening of myasthenia gravis, most lipid parameters were not associated with changes in the clinical course and severity of myasthenia gravis.we observed that lower levels of lipoprotein(a) were associated with a better prognosis in the interval 7–58 nml/L, whereas beyond this interval this was not observed, suggesting dyslipidemia may impact MG prognosis. Further studies are required to validate these findings.

Abstract Mutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2 -I1254T knock-in mice. Finally, exogenous expression of C79 improves autism-like phenotypes in the Cntnap2 -I1254T knock-in and Cntnap2 −/− knockout mice. This data demonstrates that the α-secretase is essential for CNTNAP2 processing and its function. Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis, and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

Background: Early detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). Methods: We conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy. Results: Serum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907). Conclusions: Our study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC.

Abstract Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain‐associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg−1) in alleviating pain‐associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety‐like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress‐related hormones including corticosterone, corticotropin‐releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety‐reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ‐aminobutyric acid type A receptor β3 (GABAAβ3) subunits in PVNCRH neurons diminished the anxiety‐relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain‐associated anxiety‐like behaviors using a single dose of propofol.

Abstract Currently, high-yield gas reservoirs have been discovered by exploring Lower Paleozoic tight carbonate oil and gas reservoirs in the Changqing area. These reservoirs, however, are impacted by subsequent karstification and diagenesis processes, leading to the formation of complex pore spaces with varying pore diameters ranging from microns to millimeters. Conventional well curves, with a resolution at the decimeter level, can only provide an overview of the reservoir porosity, making it challenging to evaluate the pore structure. On the other hand, electrical imaging logging data has a sampling interval of 0.1 inches and a resolution as fine as 5 mm, providing valuable information for pore structure evaluation in tight reservoirs. Since formation resistivity is influenced by factors like porosity, mud filtrate resistivity, and cementation, the cementation index serves as a reflection of the pore structure. Therefore, by calibrating the cementation index using data obtained from experiments at different scales, the pore structure parameters of tight carbonate reservoirs can be evaluated. This study conducted a comparison between numerous core experiments at various scales and both conventional and imaging log data. A method was proposed for extracting pore size distribution characteristics and calculating the pore size spectrum based on electrical imaging logging, ultimately leading to the establishment of a quantitative evaluation model for the pore structure of tight carbonate reservoirs. The results demonstrated improved accuracy and consistency in interpretation, as confirmed by well test data.

Abstract Background Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta‐analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. Methods We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false‐positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen‐2 were analyzed for functional annotations. Results Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50–0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70–3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21–1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71–2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52–3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. Conclusions The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Abstract As the most prevalent neurodevelopmental disorders in children, autism spectrum disorders (ASD) are characterized by deficits in language development, social interaction, and repetitive behaviors or inflexible interests. Contactin associated protein like 2 (CNTNAP2), encoding a single transmembrane protein (CNTNAP2) with 1331 amino acid residues, is a widely validated ASD-susceptible gene. Cntnap2-deficient mice also show core autism-relevant behaviors, including the social deficits and repetitive behavior. However, the cellular mechanisms underlying dysfunction CNTNAP2 and ASD remain elusive. In this study, we found a motif within the transmembrane domain of CNTNAP2 was highly homologous to the γ-secretase cleavage site of amyloid-β precursor protein (APP), suggesting that CNTNAP2 may undergo proteolytic cleavage. Further biochemical analysis indicated that CNTNAP2 is cleaved by γ-secretase to produce the CNTNAP2 intracellular domain (CICD). Virally delivery of CICD to the medial prefrontal cortex (mPFC) in Cntnap2-deficient (Cntnap2 −/− ) mice normalized the deficit in the ASD-related behaviors, including social deficit and repetitive behaviors. Furthermore, CICD promoted the nuclear translocation of calcium/calmodulin-dependent serine protein kinase (CASK) to regulate the transcription of genes, such as Prader Willi syndrome gene Necdin. Whereas Necdin deficiency led to reduced social interaction in mice, virally expression of Necdin in the mPFC normalized the deficit in social preference of Cntnap2 −/− mice. Our results thus reveal a critical function of CICD and highlight a role of the CNTNAP2-CASK-Necdin signaling pathway in ASD.

Abstract Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) viral load and anti‐SARS‐CoV‐2 antibodies in coronavirus disease 2019 (COVID‐19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double‐blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID‐19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum SARS‐CoV‐2 viral load and serum anti‐SARS‐CoV‐2 antibodies at baseline as biomarkers for clinical outcomes in patients enrolled in these trials. In adjusted Cox proportional hazard models, serum viral load was a more reliable predictor of clinical outcomes than NP viral load; high serum viral load was associated with higher risk for death and mechanical ventilation/death and lower likelihood of hospital discharge (high vs. negative viral load hazard ratios [95% confidence interval {CI}] were 2.87 [1.57–5.25], 3.86 [2.23–6.68], and 0.23 [0.14–0.36], respectively, in COVACTA and 8.11 [2.95–22.26], 10.29 [4.5–23.55], and 0.21 [0.15–0.29], respectively, in REMDACTA) and high serum viral load correlated with levels of inflammatory cytokines and lung damage biomarkers. High anti‐SARS‐CoV‐2 spike protein antibody (ACOV2S) levels were associated with higher likelihood of hospital discharge (high vs. below the limit of quantification hazard ratios [95% CI] were 2.55 [1.59–4.08] for COVACTA and 1.54 [1.13–2.09] for REMDACTA). These results support the role of baseline SARS‐CoV‐2 serum viral load and ACOV2S antibody titers in predicting clinical outcomes for patients hospitalized with COVID‐19.

Whole grains retain the nutrients found in whole grains, which can help maintain a healthy weight and reduce the risk of cardiovascular disease, type Ⅱ diabetes, bowel cancer and other diseases when eaten regularly. However, whole grain is difficult to be accepted by consumers due to its poor palatability and cooking characteristics. Therefore, it is necessary to improve traditional processing technology and develop new whole grain foods. As a whole grain food, grain tea not only improve the taste of whole grain, but also retain nutritional value and health effect. This paper reviews research on the changes of flavor substances and functional properties of grain tea by baking, sprouting and fermentation. In addition, the formation mechanism and inhibition methods of acrylamide and end-products of advanced glycation during the processing of grain tea discussed. This paper would provide theoretical reference for the development and utilization of whole grain drinks.

Different color protection agents were used to soak and spray the asparagus for color protection due to improve and compare the browning problem of asparagus during the process of hot air, vacuum freezing and microwave drying. The results showed that the quality of nutrition and color of asparagus powder with color protection was better than that without color protection. The color protection effect of Hu3 was significantly better than that of Hu2 and Hu1 (P

Due to the requirements for quality testing and breeding Tartary buckwheat (Fagopyrum tartaricum Gaerth), it is necessary to find a method for the rapid detection of starch content in Tartary buckwheat. To obtain samples with a continuously distributed chemical value, stable Tartary buckwheat recombinant inbred lines were used. After scanning the near-infrared spectra of whole grains, we employed conventional methods to analyze the contents of Tartary buckwheat. The results showed that the contents of total starch, amylose, amylopectin, and resistant starch were 532.1–741.5 mg/g, 176.8–280.2 mg/g, 318.8–497.0 mg/g, and 45.1–105.2 mg/g, respectively. The prediction model for the different starch contents in Tartary buckwheat was established using near-infrared spectroscopy (NIRS) in combination with chemometrics. The Kennard–Stone algorithm was used to split the training set and the test set. Six different methods were used to preprocess the spectra in the wavenumber range of 4000–12,000 cm−1. The Competitive Adaptive Reweighted Sampling algorithm was then used to extract the characteristic spectra, and the prediction model was built using the partial least squares method. Through a comprehensive analysis of each parameter of the model, the best model for the prediction of each nutrient was determined. The correlation coefficient of calibration (Rc) and the correlation coefficient of prediction (Rp) of the best models for total starch and amylose were greater than 0.95, and the Rc and Rp of the best models for amylopectin and resistant starch were also greater than 0.93. The results showed that the NIRS-based prediction model fulfilled the requirement for the rapid determination of Tartary buckwheat starch, thus providing an effective technical approach for the rapid and non-destructive testing of starch content in the food science and agricultural industry.

According to the requirements of Tartary buckwheat breeding, it is necessary to develop a method for the rapid detection of functional substances in seeds. To ensure a diverse sample pool, we utilized the stable recombinant inbred lines (RILs) of Tartary buckwheat. The coefficients of variation of the total flavonoid, vitamin E (VE), and GABA contents of the RIL population were 15.06, 16.53, and 36.93, respectively. Subsequently, we established prediction models for the functional substance contents in Tartary buckwheat using near-infrared spectroscopy (NIRS) combined with chemometrics. The Kennard–Stone algorithm divided the dataset into training and test sets, employing six different methods for preprocessing spectra. The Competitive Adaptive Reweighted Sampling algorithm extracted the characteristic spectra. The best models for total flavonoid and VE were normalized using the first derivative. The calibration correlation coefficient (Rc) and prediction correlation coefficient (Rp) of the total flavonoid and VE prediction models were greater than 0.94. The optimal GABA prediction model underwent preprocessing via normalization combined with the standard normal variate, and the Rc and Rp values were greater than 0.93. The results demonstrated that the NIRS-based prediction model could satisfy the requirements for the rapid determination of total flavonoids, VE, and GABA in Tartary buckwheat seeds.

Tryptase, the most abundant mast cell granule protein, is elevated in severe asthma patients independent of type 2 inflammation status. Higher active β tryptase allele counts are associated with higher levels of peripheral tryptase and lower clinical benefit from anti-IgE therapies. Tryptase is a therapeutic target of interest in severe asthma and chronic spontaneous urticaria. Active and inactive allele counts may enable stratification to assess response to therapies in asthmatic patient subpopulations. Tryptase gene loci TPSAB1 and TPSB2 have high levels of sequence identity, which makes genotyping a challenging task. Here, we report a targeted next-generation sequencing (NGS) assay and downstream bioinformatics analysis for determining polymorphisms at tryptase TPSAB1 and TPSB2 loci. Machine learning modeling using multiple polymorphisms in the tryptase loci was used to improve the accuracy of genotyping calls. The assay was tested and qualified on DNA extracted from whole blood of healthy donors and asthma patients, achieving accuracy of 96%, 96% and 94% for estimation of inactive α and βΙΙΙFS tryptase alleles and α duplication on TPSAB1, respectively. The reported NGS assay is a cost-effective method that is more efficient than Sanger sequencing and provides coverage to evaluate known as well as unreported tryptase polymorphisms.

AbstractPurpose Due to the poor and unpredictable prognosis of breast cancer (BC) patients with bone metastasis, it is necessary to find convenient and available prognostic predictors. This study aimed to recognize the clinical and prognostic factors related to clinical laboratory examination and to construct a prognostic nomogram for BC bone metastasis.Methods We retrospectively analyzed 32 candidate indicators from clinical features and laboratory examination data of 276 BC patients with bone metastasis. Univariate and multivariate regression analyses were performed to identify significant prognostic factors related to BC with bone metastasis. Nomogram was constructed and estimated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.Results Patients were randomly grouped into training (n = 197) and validation cohorts (n = 79). In training cohort, the multivariate regression analysis revealed that age, other organ metastasis sites, serum level of lactate dehydrogenase, globulin, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and monocyte ratio were independent prognostic factors for BC with bone metastasis. The prognostic nomogram in training cohort exhibited areas under the ROC curve (AUCs) of 0.797, 0.782, and 0.794, respectively, for predicting 1-, 3-, and 5-year overall survival. In validation cohort, the nomogram still showed acceptable discrimination ability (AUCs: 0.723, 0.742, and 0.704) and calibration.Conclusion This study constructed a novel prognostic nomogram for BC patients with bone metastasis. It could serve as a potential tool of survival assessment to help individual treatment decision-making for clinicians.

Abstract Objective The aim of this meta‐analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence‐based information for their potential predictive value of efficacy. Methods We searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted. Results Eleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD‐L1) positive: objective response rate (ORR) (relative risk [RR] = 1.39, 95% CI [0.48, 4.03], p = 0.54), with high heterogeneity (p = 0.05, I2 = 56%); disease control rate [DCR] (RR = 1.31, 95% CI [0.04, 38.57], p = 0.88), with high heterogeneity (p = 0.04, I2 = 75%); overall survival (OS) (HR = 0.89, 95% CI [0.74, 1.07], p = 0.22); and progression‐free survival (PFS) (HR = 0.83, 95% CI [0.59, 1.16], p = 0.27), with high heterogeneity (p = 0.005, I2 = 73.1%). TMB‐High (TMB‐H): OS (HR = 0.86, 95% CI [0.74, 1.00], p = 0.05); PFS (HR = 0.71, 95% CI [0.6, 0.85], p upper limit of normal (ULN): OS (HR = 0.95, 95% CI [0.81, 1.11], p = 0.511). Asian patients: OS (HR = 0.87, 95% CI [0.72, 1.04], p = 0.135); White/Non‐Asian patients: OS (HR = 0.83, 95% CI [0.76, 0.90], p

Abstract Tryptase, a protease implicated in asthma pathology, is secreted from mast cells upon activation during an inflammatory allergic response. MTPS9579A is a novel monoclonal antibody that inhibits tryptase activity by irreversibly dissociating the active tetramer into inactive monomers. This study assessed the relationship between MTPS9579A concentrations in healthy subjects and tryptase levels in serum and nasal mucosal lining fluid from healthy subjects and patients with moderate‐to‐severe asthma. These data were used to develop a mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model that quantitatively inter‐relates MTPS9579A exposure and inhibition of active tryptase in the airway of patients with asthma. From initial estimates of airway tryptase levels and drug partitioning, the PK/PD model predicted almost complete neutralization of active tryptase in the airway of patients with asthma with MTPS9579A doses of 900 mg and greater, administered intravenously (i.v.) once every 4 weeks (q4w). Suppression of active tryptase during an asthma exacerbation event was also evaluated using the model by simulating the administration of MTPS9579A during a 100‐fold increase in tryptase secretion in the local tissue. The PK/PD model predicted that 1800 mg MTPS9579A i.v. q4w results in 95.7% suppression of active tryptase at the steady‐state trough concentration. Understanding how the exposure‐response relationship of MTPS9579A in healthy subjects translates to patients with asthma is critical for future clinical studies assessing tryptase inhibition in the airway of patients with moderate‐to‐severe asthma.

The research is aim to screen out a technology which is suitable for producing a kind of raw purple sweet potato flour (RPSPF) with high anthocyanin content and low gelatinization degree (GD) in industry. Therefore, the changes of anthocyanins, GD, sensory score and comprehensive score of purple sweet potato flour (PSPF) prepared by hot-air drying (HD), microwave drying (MD), and combined hot-air and microwave drying (HD-MD) were measured and analyzed. The results showed that the optimal HD condition was 40 ℃ for 8 h. At the moment, the anthocyanin content was 1.648 mg/g, the GD was 23.39%, and the comprehensive score was 97.01 points. It had the best quality but took a lot of time. The optimal MD condition was 420 W for 10 min, the anthocyanin content of PSPF was 2.645 mg/g, the GD rose to 93.33%, and the comprehensive score was 82.00 points. But the GD of PSPF prepared by MD was widely too high to produce RPSPF. The optimal HD-MD was 50 ℃ drying to the 40% moisture content, and then converted to 280 W microwave drying the moisture content to less than 8%. Then the anthocyanin content was 1.161 mg/g, the GD was 59.11%, and the comprehensive score of PSPF was 84.04 points. HD-MD has a simple operation and control. In addition, it can ensure the quality of RPSPF on the premise of extremely shortening the drying time. In conclusion, HD-MD is suitable for rapid industrial production.

Abstract Study objectives To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. Methods An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. Results Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. Conclusions Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Abstract To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.

Buckwheat was micronized and mixed with wheat flour. The addition (0~20%) of micronized buckwheat powder on the solvent retention capacity (SRC), pasting, thermo-mechanical of mixed flour, cooking and texture properties of noodle were systematically studied. The results indicated that sucrose SRC, sodium carbonate SRC and lactic acid SRC significantly increased with the increasing of micronized buckwheat powder addition (P

Summary: Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Summary: High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. We identified markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury that predict disease severity and clinical outcomes. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab and identified novel pharmacodynamic biomarkers. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysregulation associated with severe COVID-19, indicating greater anti-inflammatory activity relative to placebo and potentially leading to faster recovery in patients hospitalized with COVID-19.

The chemical composition discrepancies of five sweet potato leaves (SPLs) and their phenolic profile variations during in vitro digestion were investigated. The results indicated that Ecaishu No. 10 (EC10) provided better retention capacity for phenolic compounds after drying. Furthermore, polyphenols were progressively released from the matrix as the digestion process proceeded. The highest bioaccessibility of polyphenols was found in EC10 intestinal chyme at 48.47%. For its phenolic profile, 3-, 4-, and 5-monosubstituted caffeoyl quinic acids were 9.75%, 57.39%, and 79.37%, respectively, while 3,4-, 3,5-, and 4,5-disubstituted caffeoyl quinic acids were 6.55, 0.27 and 13.18%, respectively. In contrast, the 3,4-, 3,5-, 4,5-disubstituted caffeoylquinic acid in the intestinal fluid after dialysis bag treatment was 62.12%, 79.12%, and 62.98%, respectively, which resulted in relatively enhanced bioactivities (DPPH, 10.51 μmol Trolox/g; FRAP, 8.89 μmol Trolox/g; ORAC, 7.32 μmol Trolox/g; IC50 for α-amylase, 19.36 mg/g; IC50 for α-glucosidase, 25.21 mg/g). In summary, desirable phenolic acid release characteristics and bioactivity of EC10 were observed in this study, indicating that it has potential as a functional food ingredient, which is conducive to the exploitation of the sweet potato processing industry from a long-term perspective.

Abstract Background Esophagogastric junction adenocarcinoma (EJA) lacks serum biomarkers to assist in diagnosis and prognosis. Here, we aimed to evaluate the diagnostic and prognostic value of serum insulin-like growth factor binding protein 3 (IGFBP3) in EJA patients. Methods 320 participants were recruited from November 2016 to January 2020, who were randomly divided into a training cohort (112 normal controls and 102 EJA patients including 24 early-stage patients) and a validation cohort (56 normal controls and 50 EJA patients including 12 early-stage patients). We used receiver operating characteristics curve (ROC) to evaluate diagnostic value. The predictive performance of the nomogram was evaluated by the concordance index (C-index). Results Serum IGFBP3 levels were significantly lower in early-stage EJA or EJA patients than those in controls (P