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Abstract Background Pepper Phytophthora blight is a devastating disease during the growth process of peppers, significantly affecting their yield and quality. Accurate, rapid, and non-destructive early detection of pepper Phytophthora blight is of great importance for pepper production management. This study investigated the possibility of using multispectral imaging combined with machine learning to detect Phytophthora blight in peppers. Peppers were divided into two groups: one group was inoculated with Phytophthora blight, and the other was left untreated as a control. Multispectral images were collected at 0-h samples before inoculation and at 48, 60, 72, and 84 h after inoculation. The supporting software of the multispectral imaging system was used to extract spectral features from 19 wavelengths, and textural features were extracted using a gray-level co-occurrence matrix (GLCM) and a local binary pattern (LBP). The principal component analysis (PCA), successive projection algorithm (SPA), and genetic algorithm (GA) were used for feature selection from the extracted spectral and textural features. Two classification models were established based on effective single spectral features and significant spectral textural fusion features: a partial least squares discriminant analysis (PLS_DA) and one-dimensional convolutional neural network (1D-CNN). A two-dimensional convolutional neural network (2D-CNN) was constructed based on five principal component (PC) coefficients extracted from the spectral data using PCA, weighted, and summed with 19-channel multispectral images to create new PC images. Results The results indicated that the models using PCA for feature selection exhibit relatively stable classification performance. The accuracy of PLS-DA and 1D-CNN based on single spectral features is 82.6% and 83.3%, respectively, at the 48h mark. In contrast, the accuracy of PLS-DA and 1D-CNN based on spectral texture fusion reached 85.9% and 91.3%, respectively, at the same 48h mark. The accuracy of the 2D-CNN based on 5 PC images is 82%. Conclusions The research indicates that Phytophthora blight infection can be detected 48 h after inoculation (36 h before visible symptoms). This study provides an effective method for the early detection of Phytophthora blight in peppers.

Mulberry (Morus alba L.) twigs are a traditional Chinese medicine and edible agricultural by-product. Oxyresveratrol (OXY) is one of the natural resorcinol-type polyphenols obtained from mulberry twigs with anti-melanogenesis effects. This study aimed to investigate the ameliorative effects and mechanisms of OXY on post-inflammatory hyperpigmentation (PIH) in vitro. The results of DPPH radical scavenging and tyrosinase inhibition assays showed that OXY exhibited potent antioxidant and tyrosinase inhibitory activities. In human melanocytes, OXY significantly down-regulated protein expression related to melanin synthesis and transport. A molecular docking study suggested that OXY could inhibit these GTPases (RAB27A, RAC1, and CDC42) activities in melanosome transfer processes. Furthermore, OXY significantly reduced inflammatory factor secretion, promoted human β-defensin production, and up-regulated the expression of barrier proteins in UVB-induced human keratinocytes. This research indicated that the OXY from mulberry twigs has potential applications in ameliorating PIH through its antioxidant, anti-melanogenic, melanosome transport inhibition, anti-inflammatory, and photoprotective properties.

The aim of this study was to explore whether and how Bacillus subtilis KC1 can enhance the growth performance of Mycoplasma gallisepticum (MG)-infected broilers. Broilers were randomly divided into 4 groups: the control group (basal diet), the MG group (basal diet + MG challenge), the KC group (basal diet + B. subtilis KC1 supplementation), the KC + MG group (basal diet + B. subtilis KC1 supplementation + MG challenge). The results showed that, compared to the control group, MG group exhibited significantly reduced body weight and average daily gain, and increased feed conversion ratio of broilers. However, compared to the MG group, the B. subtilis KC1 + MG group exhibited significantly improved above indicators of growth performance. In addition, compared to the MG group, B. subtilis KC1 + MG group exhibited increased superoxide dismutase levels and reduced levels of malondialdehyde, interleukin-1β, and tumor necrosis factor-α of broilers. Furthermore, metabolomics and transcriptomics analyses indicated that MG infection disrupted amino acid metabolism in broilers, whereas B. subtilis KC1 supplementation alleviated the abnormal amino acid metabolism caused by MG. These results suggested that B. subtilis KC1 may alleviate the poor growth performance caused by MG infection in broilers by improving amino acid metabolism.

Oxidative stress-induced neuronal damage is the main cause of neurodegenerative diseases, which is characterized by cognitive impairment. We selected a high-content natural alkaloid, trigonelline, from daily vegetables eggplants. The results showed that eggplants were rich in trigonelline. It has antioxidant and anticancer effects, but there is limited research on neurodegenerative diseases. An in vitro neuronal injury model was established using PC12 cells damaged by H2O2 to explore neuroprotective effect of trigonelline. An aging model was established in vivo by injecting D-galactose into mice for 6 weeks. Trigonelline have been found to improve cognitive impairment by improving brain-damage, enhancing antioxidant system activity in mice, regulating the activity of ChAT and AChE to maintain the balance of cholinergic system. The experimental results indicate that trigonelline has good neuroprotective effects, providing a reference for the development of functional foods made from eggplant and trigonelline, as well as prevention and treatment of neurodegenerative diseases.

ObjectiveThe involvement of immune cells in colorectal cancer (CRC) and their interplay with metabolic disorders are yet to be fully elucidated. This study examines how peripheral immune cells, inferred genetically, affect CRC and investigates the intermediary roles of metabolites.MethodsWe employed a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal influence of immune cells on CRC. Additionally, a two-step MR strategy was utilized to pinpoint potential metabolites that mediate this effect. Our analysis incorporated data from genome-wide association studies (GWAS), involving 731 immune cell types, 1,400 metabolites, and CRC outcomes. The primary method of analysis was randomized inverse variance weighting (IVW), supported by MR-Egger, weighted median, simple mode, and weighted mode analyses. Sensitivity checks were conducted using Cochran’s Q test, MR-PRESSO test, MR-Egger regression intercept, and leave-one-out analysis.ResultsThe study identified 23 immune cell types and 17 metabolites that are causally linked to CRC. Our mediation analysis highlighted that nine metabolites act as intermediaries in the relationship between nine specific immune cells and CRC risk. Notably, The ratios of Adenosine 5’-monophosphate (AMP) to aspartate and Retinol (Vitamin A) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) were found to concurrently mediate the promoting effects of Myeloid DC %DC and BAFF-R on B cells in colorectal cancer (CRC). Moreover, iminodiacetate (IDA) was found to mediate the protective effect of CD14+ CD16- monocytes on CRC, contributing 11.8% to this mediation. In contrast, IDA was also seen to decrease the protective effect of IgD+ CD38br %B cells on CRC risk, with a mediation effect proportion of -10.4%.ConclusionThis study delineates a complex network involving immune cells, metabolites, and CRC, suggesting a multifaceted pathophysiological interaction. The identified causal links and mediation pathways underscore potential therapeutic targets, providing a foundation for interventions aimed at modulating immune responses to manage CRC.

BackgroundThe association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA.MethodsSerum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves.ResultsNo significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients.ConclusionSerum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

Abstract Parkinson’s disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.

Roads are an increasingly prevalent form of human activity that drives the decrease in plant community functions and threatens global biodiversity. However, few studies have focused on the changes in the function and diversity of alpine meadows caused by road infrastructure in the Tibetan Plateau. In this study, the changes in species diversity, functional diversity, and community stability were examined at different distances from the Qinghai-Tibet highway. The results showed that the road intensified the degradation of vegetation, which significantly altered species diversity and community structure. This effect gradually decreased from near to far from the highway. Plant community cover and species diversity were highest at intermediate distances (50–100 m) from the roadway; species diversity and stability were lowest in the grassland most disturbed by the road (0 m), and species diversity and functional diversity tended to stabilize farther away from the road (250 m). Our findings indicate that changes in species diversity are synchronized with changes in functional diversity, which largely determines the outcome of degraded grassland community diversity and stability. Our results provide a reference point for restoring degraded alpine areas and mitigating the ecological impacts of roads.

BackgroundThe relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies.MethodsThis study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined.ResultsIn ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (β = −0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010–1.470), p = 0.039].ConclusionIn the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.

ObjectiveAs a spectrum of neurodegenerative conditions, dementia presents a significant challenge to worldwide health. Mild cognitive impairment (MCI) is recognized as the intermediate stage between normal cognitive functioning and dementia. Studies highlight the significant impact of dietary patterns on the management of MCI and dementia. Currently, comprehensive research on dietary patterns specific to MCI and dementia is limited, but bibliometric analysis offers a method to pinpoint essential research directions.MethodsOn November 18, 2023, a search was conducted in the Web of Science Core Collection (WoSCC) for publications on diet and MCI/dementia. Tools such as Rstudio, CiteSpace, and VOSviewer were employed to create a knowledge atlas. This atlas analyzed collaborations, reference co-citations, keyword patterns, and emerging trends.ResultsThe search yielded 1,493 publications on diet and MCI/dementia, indicating a growing interest despite fluctuations. Contributions came from 70 countries/regions and 410 organizations across 456 journals. The USA and China led in publication numbers, with significant contributions from Columbia University and Harvard Medical School. Top authors include Scarmeas Nikolaos, Morris Martha Clare, and Samieri Cecilia. The Ketogenic, Mediterranean, and MIND diets emerged as key dietary patterns for cognitive decline prevention, highlighting the role of genetic factors, especially ApoE polymorphisms, in cognitive deterioration.ConclusionThis study provides core countries, institutions, and authors in the field, and points out the development directions in the field. Future research directions in dietary for MCI and dementia will focus on: (1) the potential effects of the KD in alleviating oxidative stress and modulating gut microbiota in neurodegenerative diseases; (2) how diet influences cognitive health through patterns of ApoE and protein expression; (3) investigating the interactions between gut microbiota and brain function, known as the “gut-brain axis.”

Abstract Background Reactive astrogliosis has been demonstrated to have a role in Parkinson’s disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)’s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression. Methods A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aβ), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively. Results Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (β: 0.006, 95% CI [0.001–0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (β: 0.237, 95% CI [0.055–0.419], p = 0.011) and UPDRS-III (β: 0.676, 95% CI [0.023–1.330], p = 0.043) scores and H&Y stage (β: 0.098, 95% CI [0.047–0.149], p < 0.001) and faster decrease in MoCA (β: − 0.501, 95% CI [− 0.768 to − 0.234], p < 0.001) and FAB scores (β: − 0.358, 95% CI [− 0.587 to − 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001–1.017], p = 0.033). Conclusions Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.

Abstract Background Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown. Methods To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (Ndiscovery = 2,272, Nreplication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter assay and RT-qPCR were performed to explore the regulatory effect of the target variant. Results The total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO. Conclusions Collective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.

The landscape of pharmacological treatment for Alzheimer’s disease (AD) has undergone significant transformations with the advent of disease-modifying therapies (DMTs) targeting β-Amyloid (Aβ) accumulation, one of the hallmark pathologies of AD. The approval and market introduction of monoclonal antibodies mark the dawn of a new era in AD therapeutics as well. Furthermore, considerable progress has also been made in the development of new drugs targeting non-Aβ and non-Tau protein pathways. These advancements are key in tackling the root causes of AD, offering hope for treatments that both relieve symptoms and slow disease progression, improving patient outcomes and quality of life. This review aims to provide a comprehensive update on the advances in drug development and application for AD, including those currently in clinical trials and those already approved for the market to treat patients.

By utilizing the properties of positive definite matrices, mathematical expectations, and positive linear functionals in matrix space, the Kantorovich inequality and Wielandt inequality for positive definite matrices and random variables are obtained. Some novel Kantorovich type inequalities pertaining to matrix ordinary products, Hadamard products, and mathematical expectations of random variables are provided. Furthermore, several interesting unified and generalized forms of the Wielandt inequality for positive definite matrices are also studied. These derived inequalities are then exploited to establish an inequality regarding various correlation coefficients and study some applications in the relative efficiency of parameter estimation of linear statistical models.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Low temperature is the most common abiotic stress factors during the eggplant cultivation in solar greenhouses. Melatonin plays important roles in plant resistance to low temperature. However, the role of melatonin in regulating chilling tolerance and extending the preharvest shelf life of eggplant fruits is still unknown. In this study, we investigated the effects of exogenous melatonin on eggplant plants and fruits in response to low temperature. Under simulated low-temperature conditions, exogenous melatonin significantly relieved the chilling symptoms of seedlings by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and relative leakage rates. These reductions were caused by higher superoxide dismutase (SOD) and catalase (CAT) activities and increased endogenous polyamine and melatonin levels compared with those in untreated seedlings. Notably, the expression levels of SOD, CAT1/2, and polyamine synthesis genes (ADC and ODC) were also increased by 100 μmol · L−1 melatonin, as well as those of genes involved in melatonin synthesis (TDC, T5H, SNAT, ASMT, and COMT) and cold regulation (COR1, CBFa/b, and ZAT2/6/12). To further investigate the effects of melatonin on eggplant leaves and fruits under natural low temperature conditions, 100 μmol · L−1 melatonin was sprayed on the functional leaves at three days before commodity maturation. Melatonin significantly alleviated chilling injury in the leaves and pericarp and extended the preharvest shelf life of the fruit by increasing the expression of COR1, CBF, ZAT2/6/12, and API5 and decreasing the expression of senescence-related genes (NCED1/2 and SAG12). Therefore, 100 μmol · L−1 melatonin improved chilling tolerance and fruit shelf life by upregulating ZAT2/6/12 to affect ROS- and senescence-related processes, which provides a reference for alleviating cold stress and extending the preharvest fruit shelf life in eggplant.

TIR1/AFB proteins are a class of auxin receptors with key roles in plant development and biotic and abiotic stress responses; several have been identified as targets of the auxin-mimicking herbicide picloram. In this study, we identified five putative TIR1/AFB gene family members in the important vegetable crop Solanum melongena (eggplant) and characterized them using bioinformatics tools and gene expression analyses. Phylogenetic analysis of the TIR1/AFBs classified them into three subgroups based on their Arabidopsis and Solanum lycopersicum homologs. AFB6 homologs were present only in S. melongena and S. lycopersicum, whereas AFB2/3 homologs were found only in Arabidopsis. One pair of S. melongena TIR1 homologs were located in syntenic regions in the genome and appeared to have arisen by segmental duplication. Promoter analysis revealed 898 cis-elements in the TIR1/AFB promoters, 125 of which were related to hormones, stress, light, or growth responses, but only SmAFB5 had a cis-acting regulatory element involved in auxin responsiveness (AuxRR-core). RNA sequencing and expression profiling showed that the TIR1/AFB genes were differentially expressed at different growth stages and in response to light, temperature, and drought. Only SmTIR1A expression was significantly induced by picloram treatment and different growth stages. TIR1/AFB expression is regulated by microRNAs (miRNAs) in other plant species, and we identified 6 or 29 miRNAs that potentially targeted the five TIR1/AFB genes on the basis of comparisons with S. lycopersicum and S. tuberosum miRNAs, respectively. Three-dimensional protein structure predictions revealed that all the TIR1/AFB proteins were very similar in structure, differing only in the numbers of alpha helices and in one angle linking an α helix and a β sheet. For measuring the function of TIR1/AFB genes in response to drought, SmAFB5 was selected, and knockdown by virus-induced gene silence (VIGS) 35S::SmAFB5 lines showed resistance to drought compared to controls. These analyses provide insight into the potential functions of TIR1/AFBs during growth and in response to stress; they highlight differences among the SmTIR1/AFBs that may be useful for eggplant breeding.

BackgroundImmune-mediated necrotizing myopathies (IMNM) is a rare disease that was first described in 2004. Due to the lack of large case series, there are no formal treatment recommendations for IMNM.MethodsWe presented a case of a 47-year-old woman who experienced progressive limb weakness, starting from the lower limbs and gradually affecting the upper limbs. She also reported experiencing dyspnea after engaging in daily activities. When she was admitted to the hospital, her upper limbs were almost unable to move and she could not stand even with support. Her Creatine kinase (CK) level significantly increased (> 3500 u/l). Electromyography showed myogenic damage, anti-Signal recognition particle (anti-SRP) and anti-Ro52 antibodies were highly positive. Pathological biopsy of the right biceps muscle showed necrotizing myopathy in the skeletal muscle. She was ultimately diagnosed with anti-SRP IMNN, and was given monotherapy with methylprednisolone and combination therapy with immunoglobulin, but her symptoms continued to worsen. The patient refused to bear the possible further liver dysfunction and blood system damage caused by Cyclophosphamide and Rituximab, and she chose to try to use Ofatumumab (OFA).ResultsAfter receiving three doses of OFA treatment without any adverse reactions, she reported that her muscle strength had basically recovered and she was able to walk independently. The B cells in the circulatory system have been depleted, and blood markers such as liver function have consistently remained within normal range. During the follow up, her activity tolerance continued to improve.DiscussionWe have presented a severe case of SRP-IMNM in which the patient showed poor response to conventional immunotherapy. However, rapid symptom relief was achieved with early sequential use of OFA treatment. This provides a new option for the treatment of SRP-IMNM, and more large-scale studies will be needed in the future to verify our results.

Eggplant (Solanum melongena L.) is a highly nutritious and economically important vegetable crop. However, the fruit peel of eggplant often shows poor coloration owing to low-light intensity during cultivation, especially in the winter. The less-photosensitive varieties produce anthocyanin in low light or even dark conditions, making them valuable breeding materials. Nevertheless, genes responsible for anthocyanin biosynthesis in less-photosensitive eggplant varieties are not characterized. In this study, an EMS mutant, named purple in the dark (pind), was used to identify the key genes responsible for less-photosensitive coloration. Under natural conditions, the peel color and anthocyanin content in pind fruits were similar to that of wildtype ‘14-345’. The bagged pind fruits were light purple, whereas those of ‘14-345’ were white; and the anthocyanin content in the pind fruit peel was significantly higher than that in ‘14-345’. Genetic analysis revealed that the less-photosensitive trait was controlled by a single dominant gene. The candidate gene was mapped on chromosome 10 in the region 7.72 Mb to 11.71 Mb. Thirty-five differentially expressed genes, including 12 structural genes, such as CHS, CHI, F3H, DFR, ANS, and UFGT, and three transcription factors MYB113, GL3, and TTG2, were identified in pind using RNA-seq. Four candidate genes EGP21875 (myb domain protein 113), EGP21950 (unknown protein), EGP21953 (CAAX amino-terminal protease family protein), and EGP21961 (CAAX amino-terminal protease family protein) were identified as putative genes associated with less-photosensitive anthocyanin biosynthesis in pind. These findings may clarify the molecular mechanisms underlying less-photosensitive anthocyanin biosynthesis in eggplant.

ObjectivesMutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson’s disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations.MethodsA whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life.ResultsThe prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061–1.194, p

BackgroundMalnutrition is associated with poor survival in some diseases. However, the nutritional status in multiple system atrophy (MSA) is unknown, and the significance of malnutrition for the prediction of mortality in MSA has not been well established.ObjectiveWe aimed to determine the prevalence of malnutrition and the prognostic value of malnutrition in patients with early-stage MSA.MethodsPatients diagnosed with early phase MSA (disease duration

Objective: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH. Methods: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues. Results: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-β cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner. Conclusion: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.

Abstract Background Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare and devastating disease caused by pathogenic mutations in C19orf12 gene. MPAN is characterized by pathological iron accumulation in the brain and fewer than 100 cases of MPAN have been described. Although the diagnosis of MPAN has achieved a great breakthrough with the application of the whole exome gene sequencing technology, the therapeutic effect of iron chelation therapy in MPAN remains controversial. Case presentation We reported that two sisters from the same family diagnosed with MPAN had dramatically different responses to deferiprone (DFP) treatment. The diagnosis of MPAN were established based on typical clinical manifestations, physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF) and gene sequencing results. The clinical presentations of the two sisters with MPAN due to novel gene locus mutations were similar to those previously reported. There is no other difference in basic information except that the proband had a later onset age and fertility history. Both the proband and his second sister were treated with deferiprone (DFP), but they had dramatically different responses to the treatment. The proband’s condition deteriorated sharply after treatment with DFP including psychiatric symptoms and movement disorders. However, the second sister of the proband became relatively stable after receiving the DFP treatment. After four years of follow-up, the patient still denies any new symptoms of neurological deficits. Conclusion The findings of this study enriched the MPAN gene database and indicated that DFP might ameliorate symptom progression in patients without severe autonomic neuropsychiatric impairment at the early stage of the disease.

Abstract Background Recently, several rare variants of SPTLC1 were identified as disease cause for juvenile amyotrophic lateral sclerosis (ALS) by disrupting the normal homeostatic regulation of serine palmitoyltransferase (SPT). However, further exploration of the rare variants in large cohorts was still necessary. Meanwhile, SPTLC2 plays a similar role as SPTLC1 in the SPT function. Methods To explore the genetic role of SPTLC1 and SPTLC2 in ALS, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls from the Chinese population with whole exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test (SKAT-O). Results Totally 33 rare variants with minor allele frequency

Abstract Introduction Platelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aβ). Some oxidative stress markers and neurotransmitter markers were also differentially expressed in the peripheral platelets of AD. Therefore, the present study explored the differences in platelet-associated biomarkers between AD and healthy controls using meta-analysis and systematic review to reveal the value of platelet in the pathogenesis and development of AD. Methods We searched all the related studies that probed into the platelets in AD based on PubMed, Embase, and web of science databases from the establishment to November 04, 2021. Results Eighty-eight studies were included in the meta-analysis, and the platelets data of 702 AD and 710 controls were analyzed. The results of standardized mean difference (SMD) showed that platelets in AD had lower levels of APP ratio (SMD: -1.89; p

Flowering time is an important agronomic trait of Chinese cabbage with late flowering being a primary breeding objective. In our previous work, we obtained Chinese cabbage-cabbage translocation lines that contained several beneficial cabbage genes. Cabbage-specific molecular markers show that these genes were coming from chromosome C01 of cabbage. In this study, we investigated the inheritance of flowering time in a couple of translocation lines and analyzed the transmission rate of molecular markers in the offspring. Consequently, we obtained the late flowering Chinese cabbage-cabbage translocation line ‘AT7–4’ in which the flowering time was later than that of ‘85–1’ by about 7 days under 4-week vernalization. Based on previous studies of the genomes of Chinese cabbage and cabbage, we located the cabbage-specific molecular markers that were closely linked at the top of the chromosome A01 in the F2 mapping population generated by self-crossing F1s derived from a cross between the translocation line ‘AT7–4’ and Chinese cabbage ‘14–36’. Five flowering-related genes in the alien fragment were found by functional annotation and their molecular markers were developed. This study lays the foundation for the future improvement of Chinese cabbage varieties using A-C translocation lines.

Abstract Background Recently, several rare variants of TP73 were identified as potential disease cause for amyotrophic lateral sclerosis (ALS) in the European population. However, further replication was still necessary, especially in cohorts with different ethnic backgrounds. Methods To explore the genetic role of TP73 in ALS in the Asian population, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls with whole-exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test. Results Totally 24 rare variants with minor allele frequency

ABSTRACT: It has been reported that dietary administration of Bacillus subtilis KC1 is effective in alleviating lung injury induced by Mycoplasma gallisepticum (MG) infection in chickens. However, the underlying molecular mechanism of B. subtilis KC1 against MG infection is still unclear. The purpose of this study was to determine whether B. subtilis KC1 could alleviate MG infection-induced lung injury in chickens by regulating their gut microbiota. The results of this study indicate that B. subtilis KC1 supplementation has the potential to alleviate MG infection-induced lung injury as reflected by reduced MG colonization, reduced pathologic changes, and decreased production of pro-inflammatory cytokines. In addition, B. subtilis KC1 supplementation was partially effective in alleviating the gut microbiota disorder caused by MG infection. Importantly, B. subtilis KC1 enriched the beneficial Bifidobacterium animalis in gut and thus reversed indole metabolic dysfunction caused by MG infection. B. subtilis KC1 supplementation increased levels of indole, which enhanced aryl hydrocarbon receptor activation, improving barrier function and alleviating lung inflammation caused by MG. Overall, this study indicates that B. subtilis KC1 has a “gut-lung axis” mechanism that can reduce the severity of MG infection by enriching intestinal B. animalis and regulating indole metabolism.

Orthogonal matching pursuit (OMP) algorithm is a classical greedy algorithm widely used in compressed sensing. In this paper, by exploiting the Wielandt inequality and some properties of orthogonal projection matrix, we obtained a new number of iterations required for the OMP algorithm to perform exact recovery of sparse signals, which improves significantly upon the latest results as we know.

IntroductionUnderstanding the impact of deep groundwater depth on vegetation communities and soil in sand dunes with different underground water tables is essential for ecological restoration and the conservation of groundwater. Furthermore, this understanding is critical for determining the threshold value of groundwater depth that ensures the survival of vegetation.MethodThis paper was conducted in a semi-arid region in eastern China, and the effects of deep groundwater depth (6.25 m, 10.61 m, and 15.26 m) on vegetation communities and soil properties (0–200 cm) across three dune types (mobile, semi-fixed, and fixed dunes) were evaluated in a sand ecosystem in the Horqin Sandy Land.ResultsFor vegetation community, variations in the same species are more significant at different groundwater depths. For soil properties, groundwater depth negatively influences soil moisture, total carbon, total nitrogen, available nitrogen, available phosphorus concentrations, and soil pH. Besides, groundwater depth also significantly affected organic carbon and available potassium concentrations. In addition, herb species were mainly distributed in areas with lower groundwater depth, yet arbor and shrub species were sparsely distributed in places with deeper groundwater depth.DiscussionAs arbor and shrub species are key drivers of ecosystem sustainability, the adaptation of these dominant species to increasing groundwater depth may alleviate the negative effects of increasing groundwater depth; however, restrictions on this adaptation were exceeded at deeper groundwater depth.

ABSTRACT: Mycoplasma gallisepticum (MG) is dependent on its host for many nutrients due to the loss of many important metabolic pathways. Ceramide is a sphingolipid that regulates multiple cellular processes in eukaryotic cell. Several studies highlighted the crucial role of ceramide on the pathogenesis of various pathogens. This study aimed to determine whether ceramide plays a crucial role in the pathogenesis of MG. Based on an MG infection model in DF-1 cells, the results revealed that MG infection induced ceramide accumulation in DF-1 cells. Inhibiting the de novo synthesis of ceramide significantly inhibited MG proliferation and inflammatory injury caused by MG in DF-1 cells. Meanwhile, MG infection led to endoplasmic reticulum stress, and pharmacologic inhibition of endoplasmic reticulum stress prevented ceramide accumulation and MG proliferation in DF-1 cells, alleviating the inflammatory injury caused by MG. In addition, MG infection significantly promoted expression level of stromal interaction molecule 1 (STIM1), thus induced calcium overload and oxidative stress. Furthermore, inhibition of STIM1 expression partially restored calcium homeostasis and mitigated oxidative stress, thus alleviated endoplasmic reticulum stress. Importantly, the inflammatory injury caused by MG were partially ameliorated by baicalin treatment (20 µg/mL) through downregulating STIM1 expression. In summary, these results suggests that ceramide accumulation through the de novo pathway plays an important role to promote MG proliferation and baicalin can alleviate MG infection induced inflammatory injury via regulating STIM1-related oxidative stress, endoplasmic reticulum stress and ceramide accumulation in DF-1 cells.

BackgroundTo characterize the pattern of hospitalization in patients with Alzheimer's disease (AD) or Parkinson's disease (PD), and compare the differences to see whether AD patients and PD patients have a different picture of hospitalization.MethodsThe clinical features of all consecutive patients from January 2017 to December 2020 were reviewed. We identified AD patients and PD patients from an electronic database in a tertiary medical center.ResultsThe study group comprised 995 AD patients and 2,298 PD patients who were admitted to the hospital for the first time, and re-hospitalized 231 AD patients and 371 PD patients were also included. AD patients were older than PD patients when they were hospitalized (p < 0.001). AD patients had longer lengths of stay, higher re-hospitalization rates, and higher intrahospital mortality rates than PD patients during hospitalization even after adjusting age and gender. PD patients had higher levels of total cost than AD patients due to the cost of the deep brain stimulation (DBS) insertion. Hospitalizations for AD patients occurred most often in the department of geriatrics, while most PD patients were admitted to the department of neurology. Hospitalization due to the presence of comorbid conditions was much higher in AD patients, but a larger proportion of PD patients were hospitalized due to PD disease itself.ConclusionsThe present study found that AD patients and PD patients have a significantly different picture of hospitalization. It is important to implement different management for hospitalized AD and PD, and different emphasis should be given when establishing primary prevention strategies, informing care needs, and guiding healthcare resource planning.

Pepper mild mottle virus (PMMoV) poses a significant threat to pepper production because it is highly contagious and extremely persistent in soil. Despite this threat, little is known about the molecular processes that underlie plant responses to pepper mild mottle virus. Here, we performed RNA sequencing of tolerant (“17-p63”) and susceptible (“16-217”) pepper genotypes after pepper mild mottle virus or mock inoculation. Viral accumulation in systemic leaves was lower in the pepper mild mottle virus-resistant 17-p63 genotype than in the pepper mild mottle virus-sensitive 16-217 genotype, and infection symptoms were more apparent in systemic leaves of 16-217 than in those of 17-p63 at the same timepoints during the infection process. We identified 2,959 and 2,159 differentially expressed genes (DEGs) in systemic leaves of infected 16-217 and 17-p63, respectively. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes from both genotypes revealed significant enrichment of the MAPK signaling pathway, plant–pathogen interaction, and flavonoid biosynthesis. A number of differentially expressed genes showed opposite trends in relation to stress resistance and disease defense in the two genotypes. We also performed weighted gene co-expression network analysis (WGCNA) of all samples and identified modules associated with resistance to pepper mild mottle virus, as well as seven hub genes. These results identify candidate virus resistance genes and provide insight into pepper defense mechanisms against pepper mild mottle virus.

Abstract Background Dysregulation of Ectonucleoside Triphospahate Diphosphohydrolase 5 (ENTPD5) in tumors might be associated with tumor progression, while the role of ENTPD5 in the growth and metastasis of serous ovarian cancer (SOC) is still unclear. Methods ENTPD5 expression patterns in ovarian cancer tissues were analyzed by qRT-PCR and immunohistochemistry assay (IHC). Two SOC cell lines, SKOV3 and OVCAR8, were stably transfected with lentivirus to build knockdown and overexpression cell lines. Clone formation assay, collagen gel droplet culture technology, wound healing assay and flow cytometry were used to assess the migration and growth traits of SOC cells. Expression levels of ENTPD5, glucose regulated protein 78 (GRP78), eukaryotic translation initiation factor 2 alpha (eIF-2α), phosphorylated -eIF-2α and, C/EBP homologous protein (CHOP) in SOC cells were detected by Western blot. Results Compared to fallopian tube tissues, the expression of ENTPD5 was significantly higher in tumor tissues obtained from SOC patients, and positively correlated with clinical stage and metastasis. ENTPD5 knockdown robustly inhibited cell proliferation, migration, whereas ENTPD5 overexpression elicited the opposite effect on SOC cells. ENTPD5 knockdown arrested cell cycle in G0/G1 phase and increased apoptosis. Importantly, ENTPD5 knockdown was associated with significantly decreased protein levels for GRP78, CHOP, and p-eIF-2α, suggesting possible involvement of ENTPD5 in endoplasmic reticulum stress (ERS). Conclusions Our study demonstrates that ENTPD5 knockdown inhibited SOC cell proliferation, migration and restrained the activation of the GRP78/p-eIF-2α/CHOP pathway, which provides a potentially effective therapeutic target for the treatment of SOC.

Abstract The orthogonal matching pursuit (OMP) algorithm is a classical greedy algorithm widely used in compressed sensing. The number of iterations required for the OMP algorithm to perform exact the recovery of sparse signals is a fundamental problem in signal processing. In this work, by investigating the relationship between the iteration number for OMP and the signal estimation error based on the restricted isometry property, the authors obtained tighter bounds on the number of iterations required to approximately recover a sparse signal with noise and exact support recovering for the noiseless cases of OMP.

Abstract Neurodegenerative diseases are a group of disorders characterized by progressive loss of certain populations of neurons, which eventually lead to dysfunction. These diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Immune pathway dysregulation is one of the common features of neurodegeneration. Recently, there is growing interest in the specific role of T helper Th 17 cells and Interleukin-17A (IL-17A), the most important cytokine of Th 17 cells, in the pathogenesis of the central nervous system (CNS) of neurodegenerative diseases. In the present study, we summarized current knowledge about the function of Th17/IL-17A, the physiology of Th17/IL-17A in diseases, and the contribution of Th17/IL-17A in AD, PD, and ALS. We also update the findings on IL-17A-targeting drugs as potentially immunomodulatory therapeutic agents for neurodegenerative diseases. Although the specific mechanism of Th17/IL-17A in this group of diseases is still controversial, uncovering the molecular pathways of Th17/IL-17A in neurodegeneration allows the identification of suitable targets to modulate these cellular processes. Therapeutics targeting IL-17A might represent potentially novel anti-neurodegeneration drugs.

Prior studies have yielded mixed findings concerning the association between apolipoprotein E(APOE)-ε4 and serum lipids in patients with Alzheimer’s disease (AD) and healthy individuals. Some studies suggested a relationship between APOEε4 and serum lipids in patients with AD and healthy individuals, whereas others proposed that the APOEε4 allele affects lipids only in patients with AD. Our study aimed to investigate whether APOE alleles have a distinct impact on lipids in AD. We conducted a comprehensive search of the PubMed and Embase databases for all related studies that investigate APOE and serum lipids of AD from the inception to 30 May 2022. Elevated total cholesterol (TC) and low-density lipoprotein (LDL) levels were found in APOEε4 allele carriers compared with non-carriers. No significant differences were found for high-density lipoprotein (HDL) and triglyceride (TG) levels in APOEε4 allele carriers compared to non-carriers. Notably, elevated TC and LDL levels showed considerable heterogeneity between patients with AD and healthy controls. A network meta-analysis did not find a distinct effect of carrying one or two APOEε4 alleles on lipid profiles. Higher TC and LDL levels were found in APOEε4 allele carriers compared with non-carriers, and the difference was more significant in patients with AD than in healthy controls.

Objective: To investigate the serum levels of inflammatory cytokines and the correlations with Parkinson’s disease (PD) clinical symptoms.Methods: Serum levels of the cytokines, including IL-6, IL-8, and TNF-α, were measured in 273 PD patients and 91 healthy controls (HCs). The clinical manifestations of PD were assessed with nine different scales to evaluate the cognitive function, non-motor symptoms, motor symptoms, and disease severity. The differences in these inflammatory indicators were examined between PD patients and HCs, and the correlations of these inflammatory indicators with clinical variables were analyzed in PD patients.Results: Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in PD patients were higher than those in HCs, but serum interleukin-8 (IL-8) level was not significantly different from that in HCs. In PD patients, serum IL-6 level was positively correlated with age of onset, the Hamilton Depression Scale (HAMD), and the Non-Motor Symptom Scale (NMSS), UPDRS part I, part II, and part III, but it was inversely correlated with the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) scores. Serum TNF-α level was positively correlated with age of onset and H&Y stage in PD patients (p = .037), but negatively correlated with FAB scores in PD patients (p = .010). However, no associations were found between all the clinical variables and the serum IL-8 level. The forward binary logistic regression model revealed that serum IL-6 level was associated with MoCA (p = .023) and UPDRS I scores (p = .023), but no associations was found with the remaining factors. The ROC curve of TNF-α for the diagnosis of PD showed the area under the curve (AUC) was .719 (p < .05, 95% CI: .655–.784), and the critical value of TNF-α was 5.380 pg/ml, with a diagnostic sensitivity of 76.0% and a specificity of 59.3%.Conclusion: Our results suggest increased serum levels of IL-6 and TNF-α in PD, we further found that IL-6 level was associated with non-motor symptoms and cognitive dysfunction, and IL-6 may play a role in the pathophysiology of non-motor symptoms in PD. At the same time, we also propose that TNF-α has a good diagnostic value for PD despite its irrelevance to clinical symptoms.

The TIR1/AFB family of proteins is a group of functionally diverse auxin receptors that are only found in plants. TIR1/AFB family members are characterized by a conserved N-terminal F-box domain followed by 18 leucine-rich repeats. In the past few decades, extensive research has been conducted on the role of these proteins in regulating plant development, metabolism, and responses to abiotic and biotic stress. In this review, we focus on TIR1/AFB proteins that play crucial roles in plant responses to diverse abiotic and biotic stress. We highlight studies that have shed light on the mechanisms by which TIR1/AFB proteins are regulated at the transcriptional and post-transcriptional as well as the downstream in abiotic or biotic stress pathways regulated by the TIR1/AFB family.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of the upper and lower motor neurons from the motor cortex, brainstem, and spinal cord. Most ALS cases are sporadic, with 5–10% having a positive family history. Autosomal dominant polycystic kidney disease (ADPKD) is a heritable renal disease that eventually results in end-stage kidney disease. PKD1 is the most prevalent causative gene for ADPKD, accounting for ~85% of cases. Both diseases are currently considered untreatable. In this study, we report a large family that includes 10 patients with ALS phenotype, 3 asymptomatic SOD1-H47R carriers, and 6 with the ADPKD phenotype. Using whole exome sequencing, we found a novel likely pathogenic variant (p.R2787P) in PKD1 among patients with ADPKD, and a pathogenic variant (p.H47R) in SOD1 among patients with ALS. This study highlights the possibility that two different autosomal dominantly inherited diseases can co-exist independently within the same family. Phenotype—genotype correlations among these patients are also described. This research contributes novel phenotype and genotype characteristics of ALS with SOD1 mutations and ADPKD with PKD1 mutations.

Shaoxing rice wine is a notable exemplar of Chinese rice wine. Its superior quality is strongly correlated with the indigenous natural environment. The results indicated that Firmicutes (75%), Actinobacteria (15%), Proteobacteria (5%), and Bacteroidetes (3%) comprised the prevailing bacterial groups. Among the main bacterial genera, Lactobacillus was the most abundant, accounting for 49.4%, followed by Lactococcus (11.9%), Saccharopolyspora (13.1%), Leuconostoc (4.1%), and Thermoactinomyces (1.1%). The dominant fungal phyla were Ascomycota and Zygomycota. Among the dominant genera, Saccharomyces (59.3%) prevailed as the most abundant, followed by Saccharomycopsis (10.7%), Aspergillus (7.1%), Thermomyces (6.2%), Rhizopus (4.9%), Rhizomucor (2.2%), and Mucor (1.3%). The findings demonstrate that the structure of the bacterial and fungal communities remains stable in the environment, with their diversity strongly influenced by climatic conditions. The continuous fluctuations in environmental factors, such as temperature, air pressure, humidity, rainfall, and light, significantly impact the composition and diversity of microbial populations, particularly the dominant bacterial community.

Fe(III) bio-reduction provides a prospect of applying the iron redox cycle to nitrate remediation in the aquatic environment. The objective of this study was to realize multiple nitrate removals in the system containing Shewanella oneidensis MR-1 (S. oneidensis MR-1) and ferrihydrite or magnetite. The results showed that with three periods of 30 mg·L−1 NO3−-N addition, all nitrate reduction was completed within 170 h. In the first period (0–30 h) of nitrate addition, the main contribution of nitrate removal was due to the biological reduction process by S. oneidensis MR-1, accompanied by the reduction of Fe(III). During the second (45–90 h) and third periods (100–170 h) of nitrate addition, oxidation of biogenic Fe(II) coupled with the reduction of nitrate took place. This redox reaction resulted in the production of gaseous nitrogen of 47.33% and 16.8% for ferrihydrite/S. oneidensis MR-1 and magnetite/S. oneidensis MR-1 systems, respectively. In addition, nitrite, as an intermediate product, accumulated and negatively affected nitrate removal after the third addition of nitrate. By comparing the patterns of X-ray diffraction of the iron minerals before and after the bio-reduction, it was found that ferrihydrite was transformed into magnetite, while magnetite kept its original crystal form. HIGHLIGHTS Low-concentration nitrate did not inhibit the bio-reduction of Fe(III).; Nitrate was removed continuously in a microbial Fe redox cycle.; Abiotic reduction with biogenic Fe(II) was the sole process to remove TN.; Nitrite accumulated might have a negative effect on nitrate removal.;

Lung adenocarcinoma (LUAD) is a rapidly progressive malignancy, and its mortality rate is very high. In this study, we aimed at finding novel prognosis-related genes and constructing a credible prognostic model to improve the prediction for LUAD patients. Differential gene expression, mutant subtype, and univariate Cox regression analyses were conducted with the dataset from the Cancer Genome Atlas (TCGA) database to screen for prognostic features. These features were employed in the following multivariate Cox regression analysis and the produced prognostic model included the stage and expression of SMCO2, SATB2, HAVCR1, GRIA1, and GALNT4, as well as mutation subtypes of TP53. The exactness of the model was confirmed by an overall survival (OS) analysis and disease-free survival (DFS) analysis, which indicated that patients in the high-risk group had a poorer prognosis compared to those in the low-risk group. The area under the receiver operating characteristic curve (AUC) was 0.793 in the training group and 0.779 in the testing group. The AUC of tumor recurrence was 0.778 in the training group and 0.815 in the testing group. In addition, the number of deceased patients increased as the risk scores raised. Furthermore, the knockdown of prognostic gene HAVCR1 suppressed the proliferation of A549 cells, which supports our prognostic model that the high expression of HAVCR1 predicts poor prognosis. Our work created a reliable prognostic risk score model for LUAD and provided potential prognostic biomarkers.

Surface water dynamics are sensitive to climate change and anthropogenic activity, and they exert important feedback to the above two processes. However, it is unclear how climate and human activity affect surface water variation, especially in semi-arid regions, such as Horqin Sandy Land (HQSL), a typical part of the fragile region for intensive interaction of climate and land use change in northern China. We investigated the changes of spatiotemporal distribution and the influence of climatic and anthropogenic factors on Surface Water Area (SWA) in HQSL. There are 5933 Landsat images used in this research, which were processed on the Google Earth Engine cloud platform to extract water bodies by vegetation index and water index method. The results revealed that the area and number of water bodies showed a significant decrease in HQSL from 1985 to 2020. Spatially, the SWA experienced different amplitudes of variation in the Animal Husbandry Dominated Region (AHDR) and in the Agriculture Dominated Region (ADR) during two periods; many water bodies even dried up and disappeared in HQSL. Hierarchical partitioning analysis showed that the SWA of both regions was primarily influenced by climatic factors during the pre-change period (1985–2000; the mutation occurred in 2000), and human activity has become more and more significantly important during the post-change period (2001–2020). Thus, it is predictable that SWA variation in the following decades will be influenced by the interaction of climate change and human activity, even more by the later in HQSL, and the social sectors have to improve their ability to adapt to climate change by modifying land use strategy and techniques toward the sustainable development of water resources.

Abstract The purpose of this study is to compare the effect of the different physical factors on low-density lipoproteins (LDL) accumulation from flowing blood to the arterial wall of the left coronary arteries. The three-dimensional (3D) computational model of the left coronary arterial tree is reconstructed from a patient-specific computed tomography angiography (CTA) image. The endothelium of the coronary artery is represented by a shear stress dependent three-pore model. Fluid–structure interaction ( $$FSI$$ FSI ) based numerical method is used to study the LDL transport from vascular lumen into the arterial wall. The results show that the high elastic property of the arterial wall decreases the complexity of the local flow field in the coronary bifurcation system. The places of high levels of LDL uptake coincide with the regions of low wall shear stress. In addition, hypertension promotes LDL uptake from flowing blood in the arterial wall, while the thickened arterial wall decreases this process. The present computer strategy combining the methods of coronary CTA image 3D reconstruction, $$FSI$$ FSI simulation, and three-pore modeling was illustrated to be effective on the simulation of the distribution and the uptake of LDL. This may have great potential for the early prediction of the local atherosclerosis lesion in the human left coronary artery.

PurposeThe study aimed to evaluate the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in patients with cervical dystonia, and to explore the determinants of HRQoL in patients with cervical dystonia.MethodsEQ-5D-5L health state profiles were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ VAS) was used for self-rating of current health status. Multiple linear regression analysis was used to explore the factors associated with HRQoL in cervical dystonia.ResultsA total of 333 patients with cervical dystonia were enrolled in the analysis, with an average age of 44.3 years old. The most common impaired dimension of health was anxiety/depression (73.6%), followed by pain/discomfort (68.2%) and usual activities (48%). The median health utility score was 0.80, and the median EQ VAS score was 70.2. Multivariate linear regression analysis indicated that disease duration and the scores of the Hamilton Depression Rating Scale (HDRS), Pittsburgh sleep quality index (PSQI), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Part I, and TWSTRS Part III were associated with the health utility scores. After adjusting other parameters, the TWSTRS Part III score and the HDRS score were significantly associated with the EQ VAS scores (p < 0.05).ConclusionThis study evaluated HRQoL in patients with cervical dystonia using the Chinese version of the EQ-5D-5L scale. We found that, besides motor symptoms, non-motor symptoms, including depression, pain, and sleep quality, could be greater determinants of HRQoL in patients with cervical dystonia. Management of non-motor symptoms, therefore, may help improve HRQoL in patients with cervical dystonia.

BackgroundSex is an important factor in studying the relationship between the APOE gene, lipid profiles, and AD. However, few studies have focused on the effect of sex on lipids in AD and normal controls with different APOE genes.Materials and MethodsA total of 549 participants, including 298 AD patients and 251 body mass index (BMI)-matched healthy controls (HCs), were enrolled. Lipid profiles and APOE genes in both AD patients and HCs were determined.Results(1) TC and LDL were higher in AD patients than in HCs, only in APOEε4 carrying populations, but not in non-carrying populations. (2) TC and LDL were higher in APOEε4 allele carriers than in non-carriers, only in AD populations, but not in HCs. (3) The TC of APOEε2 carriers was lower than that of non-carriers in the male AD population, but not in the female AD population, female HCs, and male HCs. (4) The increased LDL level may increase the risk of AD in female people carrying APOEε4.ConclusionThe TC and LDL levels of APOEε4 carriers were higher than those of non-carriers, and the effect was more significant in the female AD population. The TC levels in APOEε2 carriers were lower than those in non-carriers, which was more significant in the male AD population.

Objectives: To investigate acute toxicity of Bajitian (Morinda officinalis) in zebrafish embryos. Methods: Zebrafish embryos at 48-h post fertilization (hpf) were exposed to Bajitian ethanol extract for 72 h. The causative action of a delay in yolk sac absorption by Bajitian was investigated by RT-PCR analysis of lipid metabolism-related microsomal triglyceride transfer protein (MTP), apolipoprotein C-II (ApoC2) and lipogenesis-related liver x receptor (LXR) genes. The effect of Bajitian eliciting an inflammatory response was studied by exposing 72 hpf myeloperoxidase (MPO): GFP transgenic zebrafish embryos to Bajitian extract for 4 h. Assessment was done by TUNEL, caspase-3/7, and RT-PCR analysis of the apoptosis related pathway B-cell lymphoma 2 associated X protein (Bax), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) genes, neutrophil development-related stem cell leukaemia (SCL) and transcription factor PU.1 genes, to reveal the causative action of Bajitian reducing neutrophils. Results: RT-PCR analysis found that Bajitian extract had no effect on the expression of MTP or ApoC2 genes, but upregulated LXR gene, which might explain the delay in yolk sac absorption. Analysis of the inflammatory response showed that compared with negative controls, Bajitian extract significantly (P