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IntroductionThis study explores the influence of artificial intelligence (A.I.) applications on the job performance of healthcare providers, based on data from standardised-trained residents in the First People’s Hospital of Yunnan Province in China.MethodsThe ordinary least squares model is employed to examine the relationship between A.I. applications and job performance. To address potential endogeneity and missing variables, we utilise the propensity score matching method and alternative regression models.ResultsThe findings indicate that the job performance of standardised-trained residents positively correlates with A.I. applications. This relationship remains robust after addressing endogenous and missing variables. Further discussion reveals that patients’ support mediates the relationship between A.I. and job performance. Under identical conditions, the job performance of female residents empowered by A.I. is found to be significantly better than that of their male counterparts. Conversely, no heterogeneity is observed regarding the impact of A.I. on the job performance of medical practitioners and clinical medical technicians.DiscussionThis study underscores the positive role of A.I. applications in enhancing the job performance of standardised-trained residents. The results highlight the mediating role of patient support and suggest gender-based differences in the efficacy of A.I. empowerment.

Alpha rhythm slowing is an important electroencephalogram(EEG) feature associated with (AD). This study aims to understand the correlation between alpha band deceleration and molecular changes from the perspective of neural computing. Considering the effect of Aβ amyloid deposition on the inhibitory changes in the thalamic, a thalamic cortical model coupled with Aβ amyloid is established. The results show that Aβ amyloid deposition may induce neurotoxicity in thalamic reticular nucleus neurons, which results in inhibitory changes in the thalamus and slows the alpha rhythm of EEG output from the thalamus. In order to understand the pathogenesis more intuitively, some numerical simulations are provided to illustrate the obtained theories. This research is helpful to understand the pathogenesis of AD, so as to provide theoretical basis for the intervention and control of the disease.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with a global incidence of 90 million cases annually. Despite the severity of this disease, there is currently no licensed vaccine against shigellosis. Shigella’s primary virulence factor is its type III secretion system (T3SS), which is a specialized nanomachine used to manipulate host cells. A fusion of T3SS injectisome needle tip protein IpaD and translocator protein IpaB, termed DBF, when admixed with the mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using a murine pulmonary model. To facilitate the production of this platform, a recombinant protein that consisted of LTA-1, the active moiety of dmLT, and DBF were genetically fused, resulting in L-DBF, which showed improved protection against Shigella challenge. To extrapolate this protection from mice to humans, we modified the formulation to provide for a multivalent presentation with the addition of an adjuvant approved for use in human vaccines. Here, we show that L-DBF formulated (admix) with a newly developed TLR4 agonist called BECC438 (a detoxified lipid A analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), formulated as an oil-in-water emulsion, has a very high protective efficacy at low antigen doses against lethal Shigella challenge in our mouse model. Optimal protection was observed when this formulation was introduced at a mucosal site (intranasally). When the formulation was then evaluated for the immune response it elicits, protection appeared to correlate with high IFN-γ and IL-17 secretion from mucosal site lymphocytes.

PurposeNephrolithiasis is thought to be a risk factor for osteoporosis, but data assessing if osteoporosis predisposes to the risk of nephrolithiasis are lacking. The present study aims to investigate whether patients with nephrolithiasis have a prominently higher prevalence of osteoporosis than the controls and vice versa via a cumulative analysis.MethodsFour databases were used to detect the eligible studies. We calculated the relative risk (RR) with a 95% confidence interval (CI) to assess the combined effect. The methodologies for conducting this study followed the PRISMA guidelines and were registered in the PROSPERO (ID: CRD42023395875),ResultsNine case-control or cohort studies with a total of 454,464 participants were finally included. Combined results indicated that there was a significantly higher prevalence of osteoporosis in patients with nephrolithiasis as compared to the general population without nephrolithiasis (overall RR from six studies= 1.204, 95%CI: 1.133 to 1.28, P< 0.001; heterogeneity: I2 = 34.8%, P= 0.162). Conversely, osteoporosis was significantly correlated to an increased risk of nephrolithiasis as compared to the controls without osteoporosis (overall RR from four studies= 1.505, 95%CI: 1.309 to 1.731, P< 0.001; I2 = 89.8%, P< 0.001). Sensitivity analysis on the two categories validated the above findings. No significant publication bias was identified in this study.ConclusionsThe present study highlighted a significantly high prevalence of osteoporosis in patients with nephrolithiasis and vice versa. This reciprocal association reminded the clinicians to conduct a regular follow-up assessment when managing patients with nephrolithiasis or osteoporosis, especially for the elderly.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023395875.

ObjectiveUnilateral biportal endoscopy (UBE) represents a relatively recent development in minimally invasive spine surgery. This study aimed to evaluate the efficacy and safety of UBE foraminotomy and diskectomy combined with piezosurgery for treating cervical spondylotic radiculopathy (CSR) with neuropathic radicular pain.MethodsWe retrospectively analyzed the outcomes in 12 patients with CSR who underwent UBE foraminotomy and diskectomy combined with piezosurgery. The intraoperative blood loss, operative time, visual analog scale (VAS) scores for the neck and arm, neck disability index (NDI) scores, and complications were recorded.ResultsPostoperative VAS scores of the neck and arm and NDI scores were significantly improved. Additionally, a postoperative CT scan revealed adequate enlargement of the cervical canal and nerve root. No specific complications occurred during surgery and the immediate postoperative period.ConclusionsThis primary study indicated that the UBE foraminotomy and diskectomy with piezosurgery is a promising technique for treating cervical spondylotic radiculopathy with neuropathic radicular pain.

BackgroundPrevious studies have suggested that dietary salt intake affects atrial fibrillation (AF); however, the causal association between them still remains unclear. Thus, we conducted this Mendelian randomization (MR) study to explore the correlation between them.MethodsGenetic instruments for dietary salt intake were from a genome-wide association study (GWAS), which included 462,630 European individuals. Summary-level data for AF were obtained from another published GWAS (22,068 cases and 116,926 controls). The inverse-variance weighting (IVW) method was performed as the primary MR analysis. Multiple MR methods, including Robust Adjusted Profile Score (MR-RAPS), maximum likelihood estimation, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted as complementary analyses. The MR-Egger regression intercept and MR-PRESSO global test were conducted to test potential horizontal pleiotropy. The IVW (Q) method and MR-Egger were performed to detect heterogeneity.ResultsOur results suggested that high dietary salt intake was significantly correlated with increased risk of AF [IVW: odds ratio (OR), 1.36; 95% confidence interval (CI), 1.04–1.77; p = 2.25E-02]. The maximum likelihood estimation (OR, 1.37; 95% CI, 1.05–1.78; p = 2.09E-02), MR-RAPS (OR, 1.37; 95% CI, 1.03–1.81; p = 2.79E-02), and MR-PRESSO method (OR, 1.36; 95% CI, 1.05–1.76; p = 2.37E-02) also showed that dietary salt intake was significantly correlated with the risk of AF.ConclusionThe findings of this study provide robust evidence supporting the correlation between dietary salt intake and the risk of AF. Future studies are required to further clarify this relationship and translate the findings into clinical and public health practice.

A 57-year-old Malay nullipara initially presented with a right breast lump that was increasing in size but defaulted follow-up. Two years later, she developed a contralateral breast lump. She only returned to the hospital when the right breast lump had become painful, 4 years from its onset. The biopsy of the right breast lump was a phylloides tumor and that of the left breast lump was a carcinoma. She had bilateral palpable axillary lymph nodes. She underwent bilateral mastectomy and axillary dissection. The pathology report confirmed the right breast lesion to be a malignant phylloides and the left breast lesion to be a carcinoma (pT3N2). She declined adjuvant treatment. A year after the surgical operation of the metachronous lesions, she had a right chest wall recurrence with widespread pulmonary metastases. She was given palliative chemotherapy but succumbed several months later.

BackgroundTakayasu arteritis (TA) is a chronic granulomatous vasculitis with unknown pathophysiology. TA with severe aortic obstruction has a poor prognosis. However, the efficacy of biologics and appropriate timing of surgical intervention remain controversial. We report a case of tuberculosis (TB)-associated TA with aggressive acute heart failure (AHF), pulmonary hypertension (PH), thrombosis, and seizure, who failed to survive after surgery.Case presentationA 10-year-old boy who developed a cough with chest tightness, shortness of breath, hemoptysis with reduced left ventricular ejection fraction, PH, and increased C-reactive protein and erythrocyte sedimentation rate was hospitalized at the pediatric intensive care unit of our hospital. He had strongly positive purified protein derivative skin test and interferon-gamma release assay result. Computed tomography angiography (CTA) showed occlusion of proximal left subclavian artery and stenosis of descending aorta and upper abdominal aorta. His condition did not improve after administration of milrinone, diuretics, antihypertensive agents, and intravenous methylprednisolone pulse followed by oral prednisone. Intravenous tocilizumab was administered for five doses, followed by two doses of infliximab, but his HF worsened, and CTA on day 77 showed complete occlusion of the descending aorta with large thrombus. He had a seizure on day 99 with deterioration of renal function. Balloon angioplasty and catheter-directed thrombolysis were performed on day 127. Unfortunately, the child's heart function continued to deteriorate and died on day 133.ConclusionTB infection may be related to juvenile TA. The biologics, thrombolysis, and surgical intervention failed to achieve the anticipated effect in our case with aggressive AHF due to severe aortic stenosis and thrombosis. More studies are needed to determine the role of biologics and surgery in such dire cases.

Thinopyrum ponticum (Podp.) Barkworth and D.R. Dewey is a decaploid species that has served as an important genetic resource for improving wheat for the better part of a century. The wheat–Th. ponticum 4Ag (4D) disomic substitution line Blue 58, which was obtained following the distant hybridization between Th. ponticum and common wheat, has been stably resistant to powdery mildew under field conditions for more than 40 years. The transfer of 4Ag into the susceptible wheat cultivar Xiaoyan 81 resulted in powdery mildew resistance, indicating the alien chromosome includes the resistance locus. Irradiated Blue 58 pollen were used for the pollination of the recurrent parent Xiaoyan 81, which led to the development of four stable wheat–Th. ponticum 4Ag translocation lines with diverse alien chromosomal segments. The assessment of powdery mildew resistance showed that translocation line L1 was susceptible, but the other three translocation lines (WTT139, WTT146, and WTT323) were highly resistant. The alignment of 81 specific-locus amplified fragments to the Th. elongatum genome revealed that 4Ag originated from a group 4 chromosome. The corresponding physical positions of every 4Ag-derived fragment were determined according to a cytogenetic analysis, the amplification of specific markers, and a sequence alignment. Considering the results of the evaluation of disease resistance, the Pm locus was mapped to the 3.79–97.12 Mb region of the short arm of chromosome 4Ag. Because of its durability, this newly identified Pm locus from a group 4 chromosome of Th. ponticum may be important for breeding wheat varieties with broad-spectrum disease resistance.

The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain–Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.

Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Siaα2-3 Gal/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.

Cadmium (Cd) is one of the most common pollutants in the environment. It can cause irreversible tissue damage and apoptosis in invertebrates. This study investigated the relationship between Cd exposure and oxidative damage and apoptosis in the ovarian cell of the clam Meretrix meretrix. The clams were exposed to different concentrations of Cd2+ (0, 1.5, 3, 6 and 12 mg L−1) for 5 days, and the accumulated level of Cd2+ in the ovarian tissue, and the degree of oxidative damage, changes in morphology and the response of apoptosis-related factors in the ovarian cell were determined. The bioaccumulation of Cd2+ and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonylation (PCO), and DNA-protein crosslinking (DPC) in the ovary were found to increase significantly when the clams were exposed to increasing concentrations of Cd2+. The structure of the ovarian tissue was severely damaged, and the ovarian cells displayed an irregular arrangement. The results of AO/EB staining and flow cytometry showed that the apoptotic rate of the ovarian cells increased with increasing Cd2+ concentrations. The activities of caspase-3, -8, -9, and the mRNA levels of p53, Bax and Caspase-3 in the ovary were also significantly increased. Furthermore, the level of p53 mRNA was positively correlated with the levels of MDA, PCO, DPC and ROS, but negatively correlated with the levels of total antioxidant capacity (T-AOC) and Bcl-2 mRNA. Taken together, these results indicated that Cd2+ exposure would result in oxidative damage and apoptosis for the ovarian cells, suggesting that Cd2+ toxicity could negatively affect the reproductive capacity of M. meretrix, thus threatening the reproductive development of the shellfish.

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has significantly improved the clinical outcomes of patients with metastatic melanoma. However, survival benefits are only observed in a subset of patients. The fibroblast growth factor receptor (FGFR) family genes are frequently mutated in melanoma, yet their impacts on the efficacy of ICIs remain unclear. Our study aimed to explore the association of FGFR mutations with ICIs efficacy in metastatic melanoma.MethodsThe Cancer Genome Atlas (TCGA) data (PanCancer Atlas, skin cutaneous melanoma (SKCM), n = 448) in cBioPortal were collected as a TCGA cohort to investigate the association between FGFR mutations and prognosis of melanoma patients. To explore the impact of FGFR mutations on the efficacy of ICIs in melanoma, clinical and tumor whole-exome sequencing (WES) data of four ICI-treated studies from cBioPortal were consolidated as an ICIs-treated cohort. Moreover, the relationship between FGFR mutations and immunogenicity (tumor mutation burden (TMB), neo-antigen load (NAL), mismatch repair (MMR)-related genes and DNA damage repair (DDR)-related genes) of melanoma was evaluated utilizing data from the ICIs-treated cohort. The influence of FGFR mutations on the tumor immune microenvironment (TIME) of melanoma was also analyzed using the TCGA cohort.ResultsIn the TCGA cohort, survival in melanoma patients with or without FGFR mutations was nearly equivalent. In the ICIs-treated cohort, patients with FGFR mutations had better survival than those without (median overall survival: 60.00 vs. 31.00 months; hazard ratio: 0.58, 95% CI: 0.42-0.80; P = 0.0051). Besides, the objective response rate was higher for patients harboring FGFR mutations (55.56%) compared to wild-type patients (22.40%) (P = 0.0076). Mechanistically, it was revealed that FGFR mutations correlated with increased immunogenicity (e.g., TMB, NAL, MMR-related gene mutations and DDR-related gene mutations). Meanwhile, FGFR mutant melanoma tended to exhibit an enhanced antitumor TIME compared with its wild-type counterparts.ConclusionsOur study demonstrated that FGFR mutations is a promising biomarker in stratifying patients with advanced melanoma who might benefit from ICIs therapy.

Neutrophils play a key role in the occurrence and development of cancer. However, the relationship between neutrophils and cancer prognosis remains unclear due to their great plasticity and diversity. To explore the effects of neutrophils on the clinical outcome of bladder cancer, we acquired and analyzed gene expression data and clinical information of bladder cancer patients from IMvigor210 cohort and The Cancer Genome Atlas dataset (TCGA) database. We established a neutrophil-based prognostic model incorporating five neutrophil-related genes (EMR3, VNN1, FCGRT, HIST1H2BC, and MX1) and the predictive value of the model was validated in both an internal and an external validation cohort. Multivariate Cox regression analysis further proved that the model remained an independent prognostic factor for overall survival and a nomogram was constructed for clinical practice. Additionally, FCGRT was identified as the key neutrophil-related gene linked to an adverse prognosis of bladder cancer. Up-regulation of FCGRT indicated activated cancer metabolism, immunosuppressive tumor environment, and dysregulated functional status of immune cells. FCGRT overexpression was also correlated with decreased expression of PD-L1 and low levels of tumor mutation burden (TMB). FCGRT predicted a poor response to immunotherapy and had a close correlation with chemotherapy sensitivity. Taken together, a novel prognostic model was developed based on the expression level of neutrophil-related genes. FCGRT served as a promising candidate biomarker for anti-cancer drug response, which may contribute to individualized prognostic prediction and may contribute to clinical decision-making.

ObjectiveTo determine the short-term effectiveness safety of baricitinib in children with refractory and/or severe juvenile dermatomyositis (rsJDM) in a real-world setting.MethodsThis was a single-center retrospective study, including 20 children with rsJDM. They were all treated using baricitinib combined with steroids and other immunosuppressive agents. The childhood myositis assessment scale (CMAS) and PRINTO remission criteria were used to evaluate the disease severity and treatment outcome at 0, 4, 12, and 24 weeks after initiation of baricitinib.ResultsThe skin rash improved in 95% of patients (19/20) at week 24, with a significant decrease of skin-DAS at weeks 12 (6.0 vs. 2.0, p < 0.05] and week 24 [6.0 vs. 1.0, p < 0.05) by median statistics. The CMAS score increased significantly at week 12 (41.0 [29.0, 44.0] vs. 46.0 [42.0, 52.0], p < 0.05) and week 24 (41.0 [29.0, 44.0] vs. 50.0 [45.0, 52.0], p < 0.05), as did the manual muscle testing (MMT)-8 score at week 24 (73.0 [610, 76.0] vs. 79.0 [77.0, 80.0], p < 0.05). At 24 weeks, the complete response (CR) and partial response (PR) were achieved in 75% (15/20) and 15% (3/20), respectively. The dose of corticosteroids (CS) decreased by 37% from the baseline (0.53 [0.42, 1.00] mg/kg) to week 12 (0.33 [0.18, 0.40] mg/kg) (p < 0.05), and by 49% at week 24 (p < 0.05). No serious side effects were observed.ConclusionBaricitinib combined with traditional immunosuppressants treatment was efficacious in rsJDM. Add-on therapy of baricitinib was helpful for tapering CS dose. No serious side effects were observed in this study.

Polycystic kidney disease (PKD) is a significant cause of end-stage kidney failure and there are few effective drugs for treating this inherited condition. Numerous aberrantly expressed non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), may contribute to PKD pathogenesis by participating in multiple intracellular and intercellular functions through post-transcriptional regulation of protein-encoding genes. Insights into the mechanisms of miRNAs and other ncRNAs in the development of PKD may provide novel therapeutic strategies. In this review, we discuss the current knowledge about the roles of dysregulated miRNAs and other ncRNAs in PKD. These roles involve multiple aspects of cellular function including mitochondrial metabolism, proliferation, cell death, fibrosis and cell-to-cell communication. We also summarize the potential application of miRNAs as biomarkers or therapeutic targets in PKD, and briefly describe strategies to overcome the challenges of delivering RNA to the kidney, providing a better understanding of the fundamental advances in utilizing miRNAs and other non-coding RNAs to treat PKD.

It is universally acknowledged that lncRNA plays an important role in the regulation of animal skeletal muscle development regulation. However, there is a lack of relevant research on lncRNA in rabbit skeletal muscle development. Thus, we explored the expression profiles of lncRNA in rabbits at three growth stages (2-week-old fetus, 6-week-old post-weaning, and 6-month-old adult) using RNA-seq. A total of 554 differentially expressed lncRNAs (235 up- and 319 down-regulated) were found between the post-weaning and fetus groups and 19 (7 up- and 12 down-regulated) between the post-weaning and adult groups and 429 (115 up- and 314 down-regulated) between the fetus and adult. The enrichment pathways in the post-weaning and fetus groups were mainly concentrated at AMPK and PI3K-Akt signaling pathways, and the co-expression results revealed that LINC-2903, LINC-2374, LINC-8591 plays a role in early maintenance of skeletal muscle development. The enriched pathways in the fetus and adult groups were mainly involved in PI3K-Akt signaling pathways with a strong association found in mTOR signaling pathways. Analysis of the co-expression results suggests that LINC-5617 may be involved in the proliferation of embryonic skeletal muscle cells, and that LINC-8613 and LINC-8705 may provide energy for postnatal skeletal muscle development. The specific roles of different lncRNAs in different developmental stages of New Zealand White rabbits obtained. This will contribute to the subsequent study on the regulatory mechanism of muscle development in New Zealand White rabbits.

The key issue at this stage is how to mine the large amount of valuable user sentiment information from the massive amount of web text and create a suitable dynamic user text sentiment analysis technique. Hence, this study offers a writing feature abstraction process based on ON-LSTM and attention mechanism to address the problem that syntactic information is ignored in emotional text feature extraction. The study found that the Att-ON-LSTM improved the micro-average F1 value by 2.27% and the macro-average F value by 1.7% compared to the Bi-LSTM model with the added attentivity mechanisms. It is demonstrated that it can perform better extraction of semantic information and hierarchical structure information in emotional text and obtain more comprehensive emotional text features. In addition, the ON-LSTM-LS, a sentiment analysis model based on ON-LSTM and tag semantics, is planned to address the problem that tag semantics is ignored in the process of text sentiment analysis. The experimental consequences exposed that the accuracy of the ON-LSTM and labeled semantic sentiment analysis model on the test set is improved by 0.78% with the addition of labeled word directions compared to the model Att-ON-LSTM without the addition of labeled semantic information. The macro-averaged F1 value improved by 1.04%, which indicates that the sentiment analysis process based on ON-LSTM and tag semantics can effectively perform the text sentiment analysis task and improve the sentiment classification effect to some extent. In conclusion, deep learning models for dynamic user sentiment analysis possess high application capabilities.

Background: Increased iron deposition in nigrosome as assessed by susceptibility-weighted imaging (SWI) is involved in the pathogenesis of Parkinson’s disease (PD). This study investigated the effects of antiparkinson drugs on iron deposition in the nigrosome of PD patients.Methods: Based on the retrospective analysis of clinical data, alterations in iron deposition in the substantia nigra were investigated in 51 PD patients across different types of therapies and in nine Parkinson-plus syndrome patients. The Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part Ⅲ/Ⅳ (UPDRS Ⅲ/Ⅳ) was utilized to evaluate motor function and complications. SWI (slice = 0.6 mm) was used to detect iron deposition in the nigrosome and substantia nigra. Nigrosome loss was scored on a 1-point nigrosome visibility scale. Visual assessment of dorsolateral nigral hyperintensity (DNH) was separately performed for each side of the nigrosome with SWI.Results: Increased UPDRS Ⅲ scores were correlated with low nigrosome scores based on correlation analysis at a disease duration of 6–12 months (r = −0.8420). The loss of the nigrosome on SWI was clearly inhibited in PD patients with a 3–5-year duration of administration of antiparkinson medications compared with no treatment. Decreased UPDRS Ⅲ scores and increased nigrosome scores were observed in the regular treatment of PD patients with a 6–7-year disease duration. For patients with Parkinson-plus syndromes, such as multiple system atrophy, iron accumulation was apparent in the corpus striatum and substantia nigra compared with that for patients with progressive supranuclear palsy.Conclusions: Early and regular treatment with antiparkinson drugs not only alleviates the chance of PD disability but also prevents the loss of DNH, namely, iron accumulation in the nigrosome.

Cyst nematodes are considered a dominant threat to yield for a wide range of major food crops. Current control strategies are mainly dependent on crop rotation and the use of resistant cultivars. Various crops exhibit single dominant resistance (R) genes that are able to activate effective host-specific resistance to certain cyst nematode species and/or populations. An example is the potato R gene Gpa2, which confers resistance against the potato cyst nematode (PCN), Globodera pallida population D383. Activation of Gpa2 results in a delayed resistance response, which is characterized by a layer of necrotic cells formed around the developing nematode feeding structure. However, knowledge about the Gpa2-induced defense pathways is still lacking. Here, we uncover the transcriptional changes and gene expression network induced upon Gpa2 activation in potato roots infected with G. pallida. To this end, in vitro-grown Gpa2-resistant potato roots were infected with the avirulent population D383 and virulent population Rookmaker. Infected root segments were harvested at 3 and 6 dpi and sent for RNA sequencing. Comparative transcriptomics revealed a total of 1,743 differentially expressed genes (DEGs) upon nematode infection, of which 559 DEGs were specifically regulated in response to D383 infection. D383-specific DEGs associated with Gpa2-mediated defense mainly relates to calcium-binding activity, salicylic acid (SA) biosynthesis, and systemic acquired resistance (SAR). These data reveal that cyst nematode resistance in potato roots depends on conserved downstream signaling pathways involved in plant immunity, which are also known to contribute to R genes-mediated resistance against other pathogens with different lifestyles.

BackgroundFacial seborrheic dermatitis (FSD), also called facial seborrheic eczema, is a common disease affecting both male and female patients worldwide. Tanshinone is the main bioactive component extracted from the Traditional Chinese Medicine Salvia miltiorrhiza Bunge, which is widely used in treating skin inflammatory diseases. It is necessary to evaluate the clinical evidence for tanshinone capsule treatment of FSD. This study aimed to evaluate the safety and effectiveness of tanshinone capsules combined with prednisone in the treatment of facial seborrheic dermatitis and to provide evidence for clinical practice.MethodsStudies were searched in PubMed, the Cochrane Library, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, and WanFang Database before October 2021. We also searched for randomized controlled clinical trials (RCT) of tanshinone capsules combined with prednisone on facial seborrheic dermatitis. The meta-analysis was conducted according to the guidelines of the Cochrane Handbook. Two reviewers regulated the research selection, data extraction, and risk of bias assessment, respectively, and a third reviewer was used for consulting when necessary. Review Manager Software 5.3 was used for meta-analysis.ResultsA total of 10 RCTs with 916 participants were included. Nine studies reported total effectiveness, five studies reported symptom score, seven studies reported adverse events, and four studies reported recurrence rate. The duration of treatment was 4 to 8 weeks. Combination therapy showed better clinical effects compared to the prednisone (OR: 5.82; 95% CI: 3.53, 9.59; p < 0.00001). Combination therapy could repair skin lesions (MD: −0.40; 95% CI: −0.51, −0.30; p < 0.00001), reduce skin erythema (MD: −0.58, 95% CI: −0.67, −0.49; p < 0.00001), relieve skin itch (MD: −0.70; 95% CI −0.77, −0.63; p < 0.00001), and desquamation score (MD: −0.64; 95% CI: −0.71, −0.56; p < 0.00001). Furthermore, combination therapy could reduce adverse events (OR: 0.46; 95% CI: 0.26, 0.84; p = 0.01) and control recurrence rate (OR: 0.22; 95% CI: 0.13, 0.36; p < 0.00001).ConclusionsCompared with prednisone, tanshinone capsules combined with prednisone may be effective in the treatment of facial seborrheic dermatitis. However, due to the high risk and ambiguity of bias in the included trials, the conclusion of this study must be interpreted carefully.

BackgroundTricuspid regurgitation after left-sided valve surgery was associated with terrible outcomes and high perioperative mortality for surgical treatment. In current years, minimally invasive isolated tricuspid valve repair is increasingly performed in our institution to address tricuspid regurgitation.MethodsThirty-seven consecutive patients with previous left-sided valve surgery underwent minimally invasive isolated tricuspid valve repair in our institution between November 2017 and December 2020. Twenty-nine patients(78.4%) were women and the mean age of patients was 58.4 ± 8.5 years. Follow-up was 100% complete with a mean follow-up time of 17.2 ± 9.5 months.ResultsBoth the in-hospital and 30-day mortalities were 2.7%. The overall NYHA class had improved significantly during the follow-up (p < 0.001). The grade of TR had decreased before discharge (p < 0.001) and during the follow-up (p < 0.001) compared with the preoperative level although severe TR was recurrent in one patient.ConclusionsMinimally invasive isolated tricuspid valve repair has acceptable early and midterm outcomes, may be the preferred surgical option to address tricuspid regurgitation after previous left-sided valve surgery when it is feasible.

Singapore grouper iridovirus (SGIV), a member of the Iridoviridae family, is an important marine cultured fish pathogen worldwide. Our previous studies have demonstrated that lipid metabolism was essential for SGIV entry and replication, but the roles of glucose metabolism during SGIV infection still remains largely unknown. In this study, we found that the transcription levels of key enzymes involved in glycolysis were regulated in varying degrees during SGIV infection based on the transcriptomic analysis. Quantitative PCR and western blot analysis also indicated that the expression of both glucose transporters (GLUT1 and GLUT2) and the enzymes of glucose metabolism (hexokinase 2, HK2 and pyruvate dehydrogenase complex, PDHX) were upregulated during SGIV infection in vivo or in vitro, suggesting that glycolysis might be involved in SGIV infection. Exogenous glucose supplementation promoted the expression of viral genes and infectious virion production, while glutamine had no effect on SGIV infection, indicating that glucose was required for SGIV replication. Consistently, pharmacological inhibition of glycolysis dramatically reduced the protein synthesis of SGIV major capsid protein (MCP) and infectious virion production, and promotion of glycolysis significantly increased SGIV infection. Furthermore, knockdown of HK2, PDHX, or GLUT1 by siRNA decreased the transcription and protein synthesis of SGIV MCP and suppressed viral replication, indicating that those enzymes exerted essential roles in SGIV replication. In addition, inhibition of mTOR activity in SGIV-infected cells effectively reduced the expression of glycolysis key enzymes, including HK2, PDHX, GLUT1, and GLUT2, and finally inhibited SGIV replication, suggesting that mTOR was involved in SGIV-induced glycolysis. Thus, our results not only provided new insights into the mechanism of how SGIV infection affects host cell glycolysis, but also contributed to further understanding of the iridovirus pathogenesis.

To accelerate the exploitation and use of marginal soils and develop salt-tolerant forage germplasm suitable for the coastal regions of China, seven lines of decaploid tall wheatgrass [Thinopyrum ponticum (Podp.) Barkworth and D. R. Dewey, 2n = 10x = 70] were transplanted under low (.3%) and high (.5%) salt conditions for a comprehensive analysis at the adult-plant stage. Differences were observed among these materials, especially in terms of grass yield, agronomic characteristics, and physiological and biochemical indices. Line C2 grew best with the highest shoot total fresh and dry weights under all conditions except for the milk-ripe stage in Dongying in 2019. The total membership value of C2 also reflected its excellent performance after transplanting. As superior germplasm, its relatively high antioxidant enzyme activities and chlorophyll a/b ratio suggested C2 may maintain normal metabolic and physiological functions under saline conditions. Furthermore, decaploid tall wheatgrass as a forage grass species has a high nutritive value beneficial for animal husbandry. Accordingly, line C2 may be used as excellent germplasm to develop salt-tolerant cultivars in the Circum-Bohai sea.

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.

BackgroundWe aimed at determining the influence of old age on lymph node metastasis (LNM) and prognosis in T1 colorectal cancer (CRC).MethodsWe collected data from eligible patients in Surveillance, Epidemiology, and End Results database between 2004 and 2015. Independent predictors of LNM were identified by logistic regression analysis. Cox regression analysis, propensity score-matched analysis, and competing risks analysis were used to analyze the associations between old age and lymph node (LN) status and to validate the prognostic value of old age on cancer-specific survival (CSS).ResultsIn total, 10,092 patients were identified. Among them, 6,423 patients (63.6%) had greater than or equal to 12 examined lymph nodes (LNE ≥12), and 5,777 patients (57.7%) were 65 years or older. The observed rate of LNM was 4.6% (15 out of 325) in T1 CRC elderly patients, with tumor size

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl4)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl4-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

A sequence of (La1-xHox)3NbO7 solid solutions were fabricated in this work, which were studied as candidate for thermal insulation materials. The lattices were identified via XRD, when SEM and EDS were used to characterize the microstructures and element distributions. The results showed that the highest modulus, hardness, and toughness of (La1-xHox)3NbO7 were 196 GPa, 9.2 GPa, and 1.6 MPa m1/2, respectively, and they accorded with the mechanical property requirements. Also, a low thermal conductivity (1.06 W m−1 K−1) and high thermal expansion coefficients (TECs: 11.3 × 10−6 K−1) were simultaneously realized in (La3/6Ho3/6)3NbO7, at high temperatures. No phase transition was detected up to 1,200°C, which proved their good high-temperature lattice stability. The intense anharmonic lattice vibrations might contribute to the outstanding thermal properties of (La1-xHox)3NbO7 ceramics. The suitable modulus, high hardness, low thermal conductivity, and high TECs of (La1-xHox)3NbO7 solid solutions proclaimed that they were exceptional thermal insulation ceramics.

Strong links between hearing and cognitive function have been confirmed by a growing number of cross-sectional and longitudinal studies. Seniors with age-related hearing loss (ARHL) have a significantly higher cognitive impairment incidence than those with normal hearing. The correlation mechanism between ARHL and cognitive decline is not fully elucidated to date. However, auditory intervention for patients with ARHL may reduce the risk of cognitive decline, as early cognitive screening may improve related treatment strategies. Currently, clinical audiology examinations rarely include cognitive screening tests, partly due to the lack of objective quantitative indicators with high sensitivity and specificity. Questionnaires are currently widely used as a cognitive screening tool, but the subject’s performance may be negatively affected by hearing loss. Numerous electroencephalogram (EEG) and magnetic resonance imaging (MRI) studies analyzed brain structure and function changes in patients with ARHL. These objective electrophysiological tools can be employed to reveal the association mechanism between auditory and cognitive functions, which may also find biological markers to be more extensively applied in assessing the progression towards cognitive decline and observing the effects of rehabilitation training for patients with ARHL. In this study, we reviewed clinical manifestations, pathological changes, and causes of ARHL and discussed their cognitive function effects. Specifically, we focused on current cognitive screening tools and assessment methods and analyzed their limitations and potential integration.

Cyst nematodes are able to infect a wide range of crop species and are regarded as a major threat in crop production. In response to invasion of cyst nematodes, plants activate their innate immune system to defend themselves by conferring basal and host-specific defense responses depending on the plant genotype. Basal defense is dependent on the detection of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), while host-specific defense mainly relies on the activation of canonical and non-canonical resistance (R) genes or quantitative trait loci (QTL). Currently, application of R genes and QTLs in crop species is a major approach to control cyst nematode in crop cultivation. However, emerging virulent cyst nematode field populations are threatening crop production due to host genetic selection by the application of a limited set of resistance genes in current crop cultivars. To counteract this problem, increased knowledge about the mechanisms involved in host-specific resistance mediated by R genes and QTLs to cyst nematodes is indispensable to improve their efficient and sustainable use in field crops. Despite the identification of an increasing number of resistance traits to cyst nematodes in various crops, the underlying genes and defense mechanisms are often unknown. In the last decade, indebt studies on the functioning of a number of cyst nematode R genes and QTLs have revealed novel insights in how plants respond to cyst nematode infection by the activation of host-specific defense responses. This review presents current knowledge of molecular and cellular mechanisms involved in the recognition of cyst nematodes, the activation of defense signaling and resistance response types mediated by R genes or QTLs. Finally, future directions for research are proposed to develop management strategies to better control cyst nematodes in crop cultivation.

Objective: To explore the emotional characteristics of counterfactual thinking (CT)-related emotion responses in patients with major depressive disorder (MDD) via the “counterfactual thinking gambling task (CTGT).”Method: Twenty-five patients with MDD (the MDD group) and twenty-five healthy controls (the HC group) with matched demographic features were included. The 17-item Hamilton Depression Scale (HAMD) and the 14-item Hamilton Anxiety Rating Scale (HAMA) were used to assess the severity of depression and anxiety symptoms. The counterfactual thinking gambling task was applied to assess the situation-focused- and behavior-focused-CT-related emotion responses in the MDD group and the HC group.Results: There was no significant difference in general demographic data between the two groups (p > 0.05). Compared with the HC group, the MDD group experienced higher levels of “disappointment” and lower levels of “joy” in the situation-focused CT paradigm (p < 0.05). However, the experience of “regret” and “relief” in the behavior-focused CT paradigm were not significantly different between the two groups (p > 0.05).Conclusions: MDD is associated with an impaired situation-focused-CT-related emotion responses, and is often accompanied by increased disappointment and decreased joy; however, behavior-focused-CT-related emotion responses are not significantly affected in MDD. This pattern may represent the characteristic CT-related emotion responses of MDD.

Background: Previous studies have indicated that childhood maltreatment (CM) may potentially influence the clinical symptomatology of obsessive-compulsive disorder (OCD). Here, we aimed to quantify the relationship between CM and obsessive-compulsive symptoms (OCS) and depressive symptoms in OCD through a meta-analysis.Method: We searched PubMed, Embase, Cochrane Library, and PsycARTICLES databases for articles reporting the association between CM and OCD on April 15, 2020. Random-effect models were used to quantify the relationship between CM and the severity of OCS and depressive symptoms in OCD.Results: Ten records with 1,611 OCD patients were included in the meta-analysis. The results revealed that CM is positively correlated with the severity of OCS [r = 0.10, 95%Confidence Interval (CI): 0.01–0.19, P = 0.04] as well as depressive symptoms in OCD (r = 0.15, 95%CI: 0.07–0.24, P = 0.0002). For the subtypes of CM, childhood emotional abuse (CEA) and childhood sexual abuse (CSA) was related with the severity of OCS (r = 0.11, 95%CI: 0.03–0.19, P = 0.009) and obsession (r = 0.13, 95%CI: 0.03–0.23, P = 0.01), respectively.Conclusion: Our meta-analysis indicates that OCD patients who suffered more CM may exhibit more severe OCS and depressive symptoms.

Infections caused by the opportunistic pathogen Pseudomonas aeruginosa can be difficult to treat due to innate and acquired antibiotic resistance and this is exacerbated by the emergence of multi-drug resistant strains. Unfortunately, no licensed vaccine yet exists to prevent Pseudomonas infections. Here we describe a novel subunit vaccine that targets the P. aeruginosa type III secretion system (T3SS). This vaccine is based on the novel antigen PaF (Pa Fusion), a fusion of the T3SS needle tip protein, PcrV, and the first of two translocator proteins, PopB. Additionally, PaF is made self-adjuvanting by the N-terminal fusion of the A1 subunit of the mucosal adjuvant double-mutant heat-labile enterotoxin (dmLT). Here we show that this triple fusion, designated L-PaF, can activate dendritic cells in vitro and elicits strong IgG and IgA titers in mice when administered intranasally. This self-adjuvanting vaccine expedites the clearance of P. aeruginosa from the lungs of challenged mice while stimulating host expression of IL-17A, which may be important for generating a protective immune response in humans. L-PaF’s protective capacity was recapitulated in a rat pneumonia model, further supporting the efficacy of this novel fusion vaccine.

MicroRNAs (miRNAs) are indispensable for the regulation of skeletal muscle. We performed RNA sequencing (RNA-seq) to establish a comprehensive miRNA profiling of goats in seven stages, namely, 45- (F45), 65- (F65), 90- (F90), 120- (F120), and 135-day (F135) fetuses, newborn (B1), and 90-day-old (B90) kids. In total, 421 known miRNAs and 228 goat novel miRNAs were identified in the data, and the average abundance of 19 miRNAs in seven stages exceeds 10,000 reads per million. Furthermore, 420 differentially expressed miRNAs (DEmiRNAs) were identified in all comparison group at seven stages, 80 of which were uniquely differentially expressed in the B1 and B90 comparison groups. Pathway analysis indicated that this group was associated with the release of muscle hypertrophy and regulation of myoblast proliferation. Besides, 305 DEmiRNAs were clustered into three significantly enriched profiles (profiles 11, 16, and 19). Function analysis revealed that profile 16 was related to muscle hypertrophy and differentiation. Profile 11 was involved in multiple enzyme activities and metabolic processes in muscle cells. And profile 19 was involved in material transport and structural stability. Two highly expressed miRNAs and three key miRNAs (chi-miR-328-3p, chi-miR-767, and chi-miR-150) of these profiles were verified to be consistent with the data by quantitative real-time PCR. These results provided a catalog of goat muscle-associated miRNAs, allowing us to better understand the transformation of miRNA roles during mammalian muscle development.

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.

Pre-implantation development is a dynamic, complex and precisely regulated process that is critical for mammalian development. There is currently no description of the role of the long noncoding RNAs (lncRNAs) during the pre-implantation stages in the goat. The in vivo transcriptomes of oocytes (n = 3) and pre-implantation stages (n=19) at seven developmental stages in the goat were analyzed by RNA sequencing (RNA-Seq). The major zygotic gene activation (ZGA) event was found to occur between the 8- and 16-cell stages in the pre-implantation stages. We identified 5,160 differentially expressed lncRNAs (DELs) in developmental stage comparisons and functional analyses of the major and minor ZGAs. Fourteen lncRNA modules were found corresponding to specific pre-implantation developmental stages by weighted gene co-expression network analysis (WGCNA). A comprehensive analysis of the lncRNAs at each developmental transition of high correlation modules was done. We also identified lncRNA-mRNA networks and hub-lncRNAs for the high correlation modules at each stage. The extensive association of lncRNA target genes with other embryonic genes suggests an important regulatory role for lncRNAs in embryonic development. These data will facilitate further exploration of the role of lncRNAs in the developmental transformation in the pre-implantation stage.

Axonal damage is recognized as an important pathological feature in the chronic progressive neurological disorder multiple sclerosis (MS). Promoting axonal regeneration is a critical strategy for the treatment of MS. Our clinical and experimental studies have shown that the Bu Shen Yi Sui formula (BSYS) promotes axonal regeneration in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, but the exact mechanism has not been thoroughly elucidated to date. In this study, we investigated the effects of BSYS and its two decomposed formulas—the Bu Shen formula (BS) and the Hua Tan Huo Xue formula (HTHX)—on brain-derived neurotrophic factor (BDNF)/TrkB and related signaling pathways to explore the mechanism by which axonal regeneration is promoted in vitro and in vivo. Damaged SH-SY5Y cells incubated with low serum were treated with BSYS-, BS-, and HTHX-containing serum, and EAE mice induced by the myelin oligodendrocyte glycoprotein (MOG)35–55 peptide were treated with BSYS. The results showed that the BSYS-containing serum markedly increased cell viability and increased the levels of growth associated protein (GAP)-43, phosphorylated (p)-cAMP-response element binding protein (CREB), BDNF, TrkB, and p-PI3K. The BS and HTHX treatments also induced the protein expression of GAP-43 and p-extracellular signal-regulated kinase (ERK) in the cells. Furthermore, the effects of BSYS on cell viability, GAP-43, p-CREB, and neurite outgrowth were clearly inhibited by LY294002, a specific antagonist of the PI3K signaling pathways. The addition of U0126 and U73122, antagonists of the ERK and PLCγ pathway, respectively, significantly inhibited cell viability and GAP-43 protein expression. Moreover, BSYS treatment significantly increased the expression of the 68-, 160-, and 200-kDa neurofilaments (NFs) of proteins and the BDNF, TrkB, PI3K, and Akt mRNA and proteins in the brain or spinal cord of mice at different stages. These results indicated that BSYS promotes nerve regeneration, and its mechanism is mainly related to the upregulation of the BDNF/TrkB and PI3K/Akt signaling pathways. BS and HTHX also promoted nerve regeneration, and this effect involved the ERK pathway.

Diarrheal diseases are a major cause of morbidity and mortality worldwide. They are most prevalent in settings with inadequate sanitation, poor hygiene and contaminated water. An important diarrheal pathogen in such settings is Shigella. No commercially available vaccine exists against shigellosis and immunity to the pathogen is serotype-restricted. We have previously shown that a polypeptide fusion of the Type Three Secretion Apparatus (T3SA) proteins IpaB and IpaD (named DBF) was efficacious as a vaccine against Shigella. Vaccination using different administration routes indicated that protection conferred by DBF did not fully correlate with antibodies. To define the immune responses involved in protection, we studied cellular responses to intranasal immunization with the DBF and the adjuvant dmLT. We found dendritic cell (DC) activation at the nasal associated lymphoid tissue (NALT). Activation markers CD86 and MHCII significantly increase in cells from immunized mice. Antigen exposure in vitro further confirmed the upregulation of CD80 and CD40 in primary dendritic cells. Animals immunized with antigen-primed dendritic cells were protected against Shigella infection, at levels comparable to the efficacy of immunization with the protein vaccine formulation. Therefore, we show that antigen-primed DCs are enough to provide immunity, and propose a mechanism of protection against Shigella spp. based on DC-mediated antigen presentation to T cells.

Stalk lodging resistance, which is mainly measured by stem diameter (SD), stalk bending strength (SBS), and rind penetrometer resistance (RPR) in maize, seriously affects the yield and quality of maize (Zea mays L.). To dissect its genetic architecture, in this study multi-locus genome-wide association studies for stalk lodging resistance-related traits were conducted in a population of 257 inbred lines, with tropical, subtropical, and temperate backgrounds, genotyped with 48,193 high-quality single nucleotide polymorphisms. The analyses of phenotypic variations for the above traits in three environments showed high broad-sense heritability (0.679, 0.720, and 0.854, respectively). In total, 423 significant Quantitative Trait Nucleotides (QTNs) were identified by mrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB methods to be associated with the above traits. Among these QTNs, 29, 34, and 48 were commonly detected by multiple methods or across multiple environments to be related to SD, SBS, and RPR, respectively. The superior allele analyses in 30 elite lines showed that only eight lines contained more than 50% of the superior alleles, indicating that stalk lodging resistance can be improved by the integration of more superior alleles. Among sixty-three candidate genes of the consistently expressed QTNs, GRMZM5G856734 and GRMZM2G116885, encoding membrane steroid-binding protein 1 and cyclin-dependent kinase inhibitor 1, respectively, possibly inhibit cell elongation and division, which regulates lodging resistance. Our results provide the further understanding of the genetic foundation of maize lodging resistance.

In the process of multi-energy system optimal scheduling, due to the high data processing requirements of the multi-energy devices and loads and the complexity of the operating states of the multi-energy devices, the scheduling optimization of the system is to some extent more difficult. To address this problem, this paper proposes a regional multi-energy system optimal scheduling model based on the theory of cloud-edge collaboration. First, based on intelligent data sensors, a cloud-edge cooperative scheduling framework of the regional multi-energy system is constructed. Then, the physical model of operating state data of multi-energy system equipment and the allocation mechanism of system scheduling tasks are studied. With the cloud service application layer and the edge computing layer as the upper and lower optimization scheduling layers, the double-layer optimization scheduling model of the regional multi-energy system is established. The objectives of the model are optimal scheduling cost and minimum delay of scheduling data transmission. The multi-objective whale optimization algorithm is used to solve the model. Finally, a simulation model is built for verification. The simulation results show that the scheduling model established in this paper can effectively improve the scheduling data processing capability and improve the economy of regional multi-energy system scheduling. [ABSTRACT FROM AUTHOR]

A 57-year-old Malay nullipara initially presented with a right breast lump that was increasing in size but defaulted follow-up. Two years later, she developed a contralateral breast lump. She only returned to the hospital when the right breast lump had become painful, 4 years from its onset. The biopsy of the right breast lump was a phylloides tumor and that of the left breast lump was a carcinoma. She had bilateral palpable axillary lymph nodes. She underwent bilateral mastectomy and axillary dissection. The pathology report confirmed the right breast lesion to be a malignant phylloides and the left breast lesion to be a carcinoma (pT3N2). She declined adjuvant treatment. A year after the surgical operation of the metachronous lesions, she had a right chest wall recurrence with widespread pulmonary metastases. She was given palliative chemotherapy but succumbed several months later. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), a type of Klebsiella pneumoniae (KP) that exhibits hypervirulence and carbapenem resistance phenotypes, can cause severe infections, both hospital- and community-acquired infections. CR-hvKP has brought great challenges to global public health and is associated with significant morbidity and mortality. There are many mechanisms responsible for the evolution of the hypervirulence and carbapenem resistance phenotypes, such as the horizontal transfer of the plasmid carrying the carbapenem resistance gene to hypervirulent Klebsiella pneumoniae (hvKP) or carbapenemase-producing Klebsiella pneumoniae (CRKP) acquiring a hypervirulence plasmid carrying a virulence-encoding gene. Notably, KP can evolve into CR-hvKP by acquiring a hybrid plasmid carrying both the carbapenem resistance and hypervirulence genes. In this review, we summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP. [ABSTRACT FROM AUTHOR]

Background: Perioperative hypersensitivity reaction (HR) is an IgE-FcϵRI-mediated hypersensitivity reaction with degranulation and activation of mast cells and basophils. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. However, it is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activation in vivo could potentially have high diagnostic and prognostic values. In the present study, we investigated EVs pelleted from serum in patients with succinylated gelatin induced HR. Methods: Extracellular vesicles (EVs) were isolated using a total exosome isolation kit and ultracentrifugation, characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. Basophils were isolated from fresh peripheral blood by negative selection using Basophil Isolation Kit II. Human mast cell line was stimulated with IL4. The expression levels of proteins related to the hypersensitive response were evaluated by Western blotting and flow Cytometer. Histamine and tryptase levels were tested using a commercial ELISA kit, and gene expression of inflammatory mediators was evaluated by qRT-PCR. The receiver operating characteristic (ROC) curve was used to evaluate the specificity and sensitivity of biomarker in predicting HR. Results: The concentration of EVs and protein expression level of CD63, FcϵRI, CD203c and tryptase were significantly (p < 0.05) increased in HR samples. The expression level of mast cell/basophil specific CD203c were significantly increased in EVs derived from serum and basophils of HR patients, and the CD203c+-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators. Moreover, the ROC curve of EVs concentration and CD203c expression indicated that CD203c+-EVs had a strong diagnostic ability for HR. Conclusion: Serum CD203c+-EVs serves as a novel diagnostic and prognostic biomarker for HR. [ABSTRACT FROM AUTHOR]