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Abstract Prostate cancer is one of the most common malignant tumors in men, and in-depth study of its gene expression patterns is crucial for understanding the formation and development of prostate cancer. Although single-cell transcriptomics has deeply explored the heterogeneous expression characteristics of prostate cancer, given that normal epithelial cells themselves have different states of differentiation, these normal differentiation characteristics may lead to confusion with heterogeneous tumor characteristics. In this study, we used single-cell data from the GEO database to analyze in detail the heterogeneity of prostate cancer tumor cells/tumor-associated epithelium cells (TAECs), with a particular focus on the differentiation state of epithelial cells in matching normal tissue. We found that after subtype pairing analysis of normal tissue and tumor tissue epithelium based on differentiation status, the characteristics identified later were not consistent with the general characteristics originally exhibited by different TAECs subpopulations. Among them, all TAECs subpopulations showed P53 enrichment and downregulation of the apoptotic pathway, and expressed higher levels of EGFR, ERBB2, interferon receptors, MIF, and cell adhesion-related signals; through transcription factor regulatory network analysis, we observed that YY1, NKX3-1, and EHF had higher transcriptional activity in TAECs subpopulations than normal epithelial cells at the same differentiation stage, while ATF3 was the opposite. Among them, YY1 may act as an upstream regulator of the MIF signaling pathway, and ATF3 is a key upstream transcriptional regulator of differentially expressed genes in the P53 and apoptotic pathways. Immune infiltration analysis showed that the above four transcription factors were significantly correlated with the infiltration of immune cells in prostate cancer, and pan-cancer analysis showed that their expression-related survival risks were widely present in different cancers. It is worth noting that this is merely a preliminary, exploratory study, which inevitably has some deficiencies and limitations. Despite this, this study is committed to bringing a novel and unique perspective to the field through this work, with the hope of opening up new levels of understanding and stimulating more in-depth research and discussion.

Abstract The environmental contamination by extremophile Aspergillus species, i.e., Aflatoxin B1, is hardly controllable in Southeast Asia and Sub-Saharan Africa, which lack handling resources and controlled storage facilities. Acute aflatoxicosis poisoning from aflatoxin-prone dietary staples could cause acute hepatic necrosis, acute liver failure, and death. Here, as the cheaper, more straightforward, and facile on-site diagnostic kit is needed, we report an ultraviolet-excitable optical aptasensor based on a fluorinated ethylene propylene film strip. Molecular dynamics on the aptamer.AFB1 complex revealed that the AFB1 to the aptamer increases the overall structural stability, suggesting that the aptamer design is suitable for the intended application. Under various influencing factors, the proposed label-free strategy offers a fast 20-min on-site fabrication simplicity and 19-day shelf-life. The one-pot incubation provides an alternative to catalytic detection and exhibited 4 times reusability. The recovery of crude brown sugar, processed peanuts, and long-grain rice were 102.74 ± 0.41 (n = 3), 86.90 ± 3.38 (n = 3), and 98.50 ± 0.42 (n = 3), comparable to High-Performance Liquid Chromatography-Photodiode Array Detector results. This study is novel owing to the peculiar UV-active spectrum fingerprint and the convenient use of hydrophobic film strips that could promote breakthrough innovations and new frontiers for on-site/forensic detection of environmental pollutants.

Abstract Background Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. Results In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3’H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6’’-O-acetyl)-glucoside, cosmosiin and apigenin-4’-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. Conclusion The findings are helpful for genetic improvement of varieties in L.macranthoides.

Abstract Background Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. Methods This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. Results There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p

Abstract Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression. Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort. Methods: Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI. Results: Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1–133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: −19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups. Conclusion: Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

Salvia miltiorrhiza Bunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1 % in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.

BackgroundInfant, junior, and adult patients with neuronal intranuclear inclusion disease (NIID) present with various types of seizures. We aimed to conduct a systematic literature review on the clinical characteristics of NIID with seizures to provide novel insight for early diagnosis and treatment and to improve prognosis of these patients.MethodsWe used keywords to screen articles related to NIID and seizures, and data concerning the clinical characteristics of patients, including demographic features, disease characteristics of the seizures, treatment responses, imaging examinations, and other auxiliary examination results were extracted.ResultsThe included studies comprised 21 patients with NIID with seizures. The most common clinical phenotypes were cognitive impairment (76.20%) and impaired consciousness (57.14%), and generalized onset motor seizures (46.15%) represented the most common type. Compared with infantile and juvenile cases, the use of antiepileptic drugs in adults led to significant seizure control and symptom improvement, in addition to providing a better prognosis. The number of GGC sequence repeats in the NOTCH2NLC gene in six NIID patients with seizures who underwent genetic testing ranged 72–134.ConclusionThe most common clinical phenotypes in patients with NIID with seizures were cognitive impairment and consciousness disorders. Patients with NIID presented with various types of seizures, with the most common being generalized onset motor seizures. Adult patients had a better prognosis and were relatively stable. The early diagnosis of NIID with seizures is of great significance for treatment and to improve prognosis.

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.

Locally Resonant Acoustic Metamaterials (LRAMs) have significant application potential because they can form subwavelength band gaps. However, most current research does not involve obtaining LRAMs with specified band gaps, even though such LRAMs are significant for practical applications. To address this, we propose a parameterized level-set-based topology optimization method that can use multiple materials to design LRAMs that meet specified frequency constraints. In this method, a simplified band-gap calculation approach based on the homogenization framework is introduced, establishing a restricted subsystem and an unrestricted subsystem to determine band gaps without relying on the Brillouin zone. These subsystems are specifically tailored to model the phenomena involved in band gaps in LRAMs, facilitating the opening of band gaps during optimization. In the multi-material representation model used in this method, each material, except for the matrix material, is depicted using a similar combinatorial formulation of level-set functions. This model reduces direct conversion between materials other than the matrix material, thereby enhancing the band-gap optimization of LRAMs. Two problems are investigated to test the method’s ability to use multiple materials to solve band-gap optimization problems with specified frequency constraints. The first involves maximizing the band-gap width while ensuring it encompasses a specified frequency range, and the second focuses on obtaining light LRAMs with a specified band gap. LRAMs with specified band gaps obtained in three-material or four-material numerical examples demonstrate the effectiveness of the proposed method. The method shows great promise for designing metamaterials to attenuate specified frequency spectra as required, such as mechanical vibrations or environmental noise.

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

Abstract Background Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS). Case presentation A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well. Conclusion We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.

The two goals of this study are to examine the impact of an early childhood teacher’s metacognition-driven, place-based science teaching professional development (PD) intervention and to explore the association between science teaching and environment quality and children’s self-regulated learning. A total of 110 children (Mage = 60 months) and 20 teachers from preschools and kindergartens in rural regions of Idaho, U.S., participated in this mixed-methods study between August 2022 and May 2023. Children’s and teachers’ pre-test and post-test data were collected using validated observation tools, surveys, and reflection journals. The results from repeated measures ANOVA and linear mixed regression show that there were statistically significant increases in children’s self-regulated learning scores and teachers’ science teaching efficacy and metacognitive knowledge, but not metacognitive regulation skill scores post-PD. Thematic analysis revealed evidence about children’s learning interests and inquiry skills, and that science activities supported children’s learning in other subjects and developmental domains (e.g., literacy, mathematics, and social-emotional skills). Our results indicate the potential for supporting young children’s self-regulated learning by training teachers to implement a developmentally appropriate, hands-on science curriculum that focuses on reflective thinking and a holistic understanding of science concepts and process skills.

Abstract As a rare and highly aggressive soft tissue sarcoma, the new immunophenotype, atypical FISH pattern and relevant molecular cytogenetics of synovial sarcoma (SS) remain less known, although it is characteristically represented by a pathognomonic chromosomal translocation t (X; 18) (p11.2; q11.2). Methodologically, the morphology was retrospectively analysed by using H&E staining, and immunohistochemical features were investigated by using markers that have been recently applied in other soft tissue tumors. Moreover, FISH signals for SS18 and EWSR-1 break-apart probes were examined. Finally, cytogenetic characteristics were analysed via RT-PCR and Sanger sequencing. Consequently, nine out of thirteen cases that were histologically highly suspected as SS were finally identified as SS via molecular analysis. Histologically, nine SS cases were divided into monophasic fibrous SS (4/9), biphasic SS (4/9) and poorly differentiated SS (1/9). Immunohistochemically, SOX-2 immunostaining was positive in eight cases (8/9) and PAX-7 immunostaining was diffusely positive in the epithelial component of biphasic SS (4/4). Nine cases showed negative immunostaining for NKX3.1 and reduced or absent immunostaining for INI-1. Eight cases showed typically positive FISH signalling for the SS18 break-apart probe, whereas one case exhibited an atypical FISH pattern (complete loss of green signalling, case 2). Furthermore, the SS18-SSX1 and SS18-SSX2 fusion genes were identified in seven cases and two cases, respectively. The fusion site in 8 out of 9 cases was common in the literature, whereas the fusion site in case 2 was involved in exon 10 codon 404 in SS18 and exon 7 codon 119 in SSX1 (which has not been previously reported), which notably corresponded to the complete loss of green signalling in the FISH pattern. Additionally, FISH analysis of the EWSR-1 gene in nine SS cases demonstrated aberrant signalling in three cases that were recognized as a monoallelic loss of EWSR-1 (1/9), an amplification of EWSR-1 (1/9) and a translocation of EWSR-1 (1/9). In conclusion, SS18-SSX fusion gene sequencing is obligatory for a precise diagnosis of SS when dealing with a confusing immunophenotype and atypical or aberrant FISH signalling for SS18 and EWSR-1 detection.

Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.

BackgroundNeuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case–control PD cohort, we evaluated the diagnostic accuracy of quantitative iron–neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association.MethodsPD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin–iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity.ResultsIn total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r |

MicroRNAs (miRNAs) are endogenous non-coding small RNA with 19–24 nucleotides (nts) in length, which play an essential role in regulating gene expression at the post-transcriptional level. As one of the first miRNAs found in plants, miR171 is a typical class of conserved miRNAs. The miR171 sequences among different species are highly similar, and the vast majority of them have both “GAGCCG” and “CAAUAU” fragments. In addition to being involved in plant growth and development, hormone signaling and stress response, miR171 also plays multiple and important roles in plants through interactions with microbe and other small-RNAs. The miRNA functions by regulating the expression of target genes. Most of miR171’s target genes are in the GRAS gene family, but also include some NSP, miRNAs, lncRNAs, and other genes. This review is intended to summarize recent updates on miR171 regarding its function in plant life and hopefully provide new ideas for understanding miR171 function and regulatory mechanisms.

α-synuclein (α-syn) is a highly conserved and thermostable protein that is widely distributed in human brain. An intracellular aggregation of α-syn in dopaminergic neurons is the hallmark of a group of neurodegenerative diseases including Parkinson’s disease. Interestingly, α-syn is also highly expressed in red blood cells and is considered as one of the most abundant proteins in red blood cells. Moreover, α-syn is thought to play a regulatory role during normal erythropoiesis. However, whether α-syn participates in the pathogenesis of erythroid diseases has not been reported. In this review, we discuss the protein structure of α-syn and the importance of α-syn in erythropoiesis.

Abstract Background Acupuncture combined with auricular acupressure has been used as a complementary and alternative treatment for smoking cessation in Hong Kong for over 10 years. This study aimed to investigate the success rates of smoking cessation posttreatment, and to evaluate treatment effects on tobacco dependence, smoking behavior, anxiety levels, and sleep disturbances between successful and unsuccessful quit smokers in Hong Kong. Methods This prospective, multicenter clinical study conducted between September 2020 and February 2022 in Hong Kong was part of the Guangdong-Hong Kong-Macau Greater Bay Area project on smoking cessation. Thirty eligible current smokers (mean age 47.10 years; 40% female) were recruited and received a combination of standardized acupuncture and auricular acupressure treatments twice weekly for 8 weeks. The primary outcome was the success rate of smoking cessation at week 24. The secondary outcomes were the success rates of smoking cessation at weeks 8 and 16, exhaled carbon monoxide (CO) levels, and changes in scores on the Fagerström Test for Nicotine Dependence (FTND), Autonomy Over Smoking Scale (AUTOS), Hamilton Anxiety Rating Scale (HAM-A), Self-rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI). Adverse events were also recorded. Results Of 30 eligible participants, 28 completed 6 or more treatment sessions; all completed follow-up assessments. At week 24, the success rate of smoking cessation was 46.67%. The successfully quit rates at weeks 8 and 16 were 36.67% and 43.33%, respectively. The overall change in mean FTND scores from baseline improved significantly from weeks 2 to 24 (P

BackgroundDeep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson’s disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years.MethodsParticipating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time.ResultsMD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores.ConclusionPallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

Coal gangue image recognition is a critical technology for achieving automatic separation in coal processing, characterized by its rapid, environmentally friendly, and energy-saving nature. However, the response characteristics of coal and gangue vary greatly under different illuminance conditions, which poses challenges to the stability of feature extraction and recognition, especially when strict illuminance requirements are necessary. This leads to fluctuating coal gangue recognition accuracy in industrial environments. To address these issues and improve the accuracy and stability of image recognition under variable illuminance conditions, we propose a novel coal gangue recognition method based on laser speckle images. Firstly, we studied the inter-class separability and intra-class compactness of the collected laser speckle images of coal and gangue by extracting gray and texture features from the laser speckle images, and analyzed the performance of laser speckle images in representing the differences between coal and gangue minerals. Subsequently, coal gangue recognition was achieved using an SVM classifier based on the extracted features from the laser speckle images. The fusion feature approach achieved a recognition accuracy of 94.4%, providing further evidence of the feasibility of this method. Lastly, we conducted a comparative experiment between natural images and laser speckle images for coal gangue recognition using the same features. The average accuracy of coal gangue laser speckle image recognition under various lighting conditions is 96.7%, with a standard deviation of the recognition accuracy of 1.7%. This significantly surpasses the recognition accuracy obtained from natural coal and gangue images. The results showed that the proposed laser speckle image features can facilitate more stable coal gangue recognition with illumination factors, providing a new, reliable method for achieving accurate classification of coal and gangue in the industrial environment of mines.

Abstract Background This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. Methods A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. Results There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P

Over the last two decades, task-based language teaching (TBLT) has been promoted as more effective for language acquisition than conventional communicative pedagogic practices in a variety of literature. However, it is unclear whether TBLT principles are integrated into English as additional language (EAL) teachers’ beliefs and how they made use of ideas announced in the TBLT literature at tertiary level in New Zealand. This exploratory study investigated whether TBLT is evident in three tertiary EAL teachers’ classes and how these teachers used tasks in language classes in New Zealand. Repeated semi-structured interviews and classroom observations were employed in this case study research. A key finding is that teachers were using a Communicative Language Teaching model rather than what they claimed to be TBLT. Furthermore, teachers did not prioritize a particular task feature, which was to have a non-linguistic outcome at the end of the task. This study contributes to our understanding of teachers’ beliefs and practices with regard to TBLT in New Zealand.

BackgroundCreutzfeldt–Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan.MethodsA total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies.ResultsAll patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected.DiscussionAll patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.

BackgroundLower-grade glioma (LGG) is one of the most common malignant tumors in the central nervous system (CNS). Accumulating evidence have demonstrated that tryptophan metabolism is significant in tumor. Therefore, this study aims to comprehensively clarify the relationship between tryptophan metabolism-related genes (TRGs) and LGGs.MethodsThe expression level of TRGs in LGG and normal tissues was first analyzed. Next, the key TRGs with prognostic value and differential expression in LGGs were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. Subsequently, a risk model was constructed and Consensus clustering analysis was conducted based on the expression level of key TRGs. Then, the prognostic value, clinicopathological factors, and tumor immune microenvironment (TIME) characteristics between different risk groups and molecular subtypes were analyzed. Finally, the expression, prognosis, and TIME of each key TRGs were analyzed separately in LGG patients.ResultsA total of 510 patients with LGG from The Cancer Genome Atlas (TCGA) dataset and 1,152 normal tissues from the Genotype-Tissue Expression (GTEx) dataset were included to evaluate the expression level of TRGs. After LASSO regression analysis, we identified six key TRGs and constructed a TRGs risk model. The survival analysis revealed that the risk model was the independent predictor in LGG patients. And the nomogram containing risk scores and independent clinicopathological factors could accurately predict the prognosis of LGG patients. In addition, the results of the Consensus cluster analysis based on the expression of the six TRGs showed that it could classify the LGG patients into two distinct clusters, with significant differences in prognosis, clinicopathological factors and TIME between these two clusters. Finally, we validated the expression, prognosis and immune infiltration of six key TRGs in patients with LGG.ConclusionThis study demonstrated that tryptophan metabolism plays an important role in the progression of LGG. In addition, the risk model and the molecular subtypes we constructed not only could be used as an indicator to predict the prognosis of LGG patients but also were closely related to the clinicopathological factors and TIME of LGG patients. Overall, our study provides theoretical support for the ultimate realization of precision treatment for patients with LGG.

BackgroundThis study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma.MethodsA total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What’s more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis.ResultsThe patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable (P

AIM: To assess changed spontaneous brain activity in hyperthyroid exophthalmos (HE) patients by the amplitude of the low-frequency fluctuation (ALFF) method, and to analyze the correlation between brain activity and ALFF values in these patients. METHODS: Totally 18 HE and 18 hyperthyroid non-exophthalmos (HNE) patients were enrolled. The participants were tested by resting-state functional magnetic resonance imaging, and receiver operating characteristic (ROC) curves were generated to classify the ALFF values of the study population. Pearson's correlation analysis was utilized to evaluate the relationship between the ALFF values obtained from different brain areas and clinical manifestations. RESULTS: Contrary to HNE patients, we observed lower ALFF values in the left calcarine fissure and surrounding cortex (LCFSC) in HE patients. In the ROC curve analysis of the LCFSC, the area under the curve reflected a high degree of accuracy. In addition, there was positive correlation between mean ALFF values of the LCFSC and the best-corrected visual acuity of the affected eyes. CONCLUSION: The study displays abnormal brain activity in LCFSC in patients with HE, which might suggest pathological mechanism of visual impairment of HE patients.

AIM: To explore the changes and influencing factors of effective optical zone(EOZ)after femtosecond laser small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:Retrospective study. From October 2019 to October 2020, fifty patients(92 eyes)with myopia who underwent SMILE surgery in the Affiliated Eye Hospital of Nanchang University and whose preoperative optical zone diameter was designed to be 6.5mm were selected. According to the preoperative equivalent spherical diopter, the patients were divided into three groups: low myopia group(-0.50D to -3.00D, 18 cases, 34 eyes), moderate myopia group(>-3.00D to -6.00D, 20 cases, 36 eyes)and high myopia group(>-6.00D, 12 cases, 22 eyes). The uncorrected visual acuity, best corrected visual acuity, manifest refraction spherical equivalent, optical zone diameter, corneal Q-value and high-order aberrations(HOA)were collected before and 3mo after operation.RESULTS:The postoperative 3mo EOZ of patients with low, moderate and high myopia were 5.07±0.69, 5.08±0.43 and 4.50±0.58 mm, respectively, and the corneal Q-values were 0.22±0.17, 0.57±0.34 and 0.63±0.73, there were significant differences among the three groups(all P

Background: Active engagement in intellectually enriching activities reportedly lowers the risk of cognitive decline; however, few studies have examined this association, including engagement in traditional cultural activities. This study aimed to elucidate the types of cultural engagement associated with lower risk of cognitive impairment. Methods: We examined the association between cultural engagement and cognitive impairment using Cox proportional hazards models in a cohort of 44,985 participants (20,772 males and 24,213 females) aged 65 years or older of the Japan Gerontological Evaluation Study from 2010 to 2016. Intellectual activities (eg, reading books, magazines, and/or newspapers), creative activities (eg, crafts and painting), and traditional cultural activities (eg, poetry composition [haiku], calligraphy, and tea ceremony/flower arrangement) were included among cultural engagement activities. Results: Over a follow-up period of 6 years, incident cognitive disability was observed in 4,198 respondents (9.3%). After adjusting for potential confounders, such as depression and social support, intellectual activities were protectively associated with the risk of cognitive impairment (hazard ratio [HR] for those who read and stated that reading was their hobby, 0.75; 95% confidence interval [CI] 0.66–0.85 and HR for those who read but did not consider reading a hobby, 0.72; 95% CI, 0.65–0.80). Engagement in creative activities was also significantly correlated with lower risk of cognitive impairment (crafts: HR 0.71; 95% CI, 0.62–0.81 and painting: HR 0.80; 95% CI, 0.66–0.96). The association between traditional cultural activities and the risk of cognitive impairment was not statistically significant. Conclusions: Engagement in intellectual and creative activities may be associated with reduced risk of dementia.

Hyperuricemic nephropathy (HN) is a common clinical complication of hyperuricemia. The pathogenesis of HN is directly related to urea metabolism in the gut microbiota. Febuxostat, a potent xanthine oxidase inhibitor, is the first-line drug used for the treatment of hyperuricemia. However, there have been few studies on the pharmacokinetics of febuxostat in HN animal models or in patients. In this study, a high-purine diet-induced HN rat model was established. The pharmacokinetics of febuxostat in HN rats was evaluated using LC-MS/MS. Astragaloside IV (AST) was used to correct the abnormal pharmacokinetics of febuxostat. Gut microbiota diversity analysis was used to evaluate the effect of AST on gut microbiota. The results showed that the delayed elimination of febuxostat caused drug accumulation after multiple administrations. Oral but not i. p. AST improved the pharmacokinetics of febuxostat in HN rats. The mechanistic study showed that AST could regulate urea metabolism in faeces and attenuate urea-ammonia liver-intestine circulation. Urease-related genera, including Eubacterium, Parabacteroides, Ruminococcus, and Clostridia, decreased after AST prevention. In addition, the decrease in pathogenic genera and increase in short-chain fatty acids (SCFA) producing genera also contribute to renal function recovery. In summary, AST improved the pharmacokinetics of febuxostat in HN rats by comprehensive regulation of the gut microbiota, including urea metabolism, anti-calcification, and short-chain fatty acid generation. These results imply that febuxostat might accumulate in HN patients, and AST could reverse the accumulation through gut microbiota regulation.

AIM: To study the postoperative optical zone decentration and visual quality by taking visual axis corneal reflect point(VACRP)and corneal vertex(CV)as the ablation center, exploring the femtosecond laser small incision lenticule extraction(SMILE).METHODS: Prospective randomized controlled trial. Totally 70 myopic patients(140 eyes)who underwent SMILE surgery in our hospital from May to June 2020 were randomly divided into two groups, 68 eyes of 34 cases took the VACRP as the ablation center(VACRP group), and 72 eyes of 36 cases took the CV as the ablation center(CV group). The visual acuity, refractive diopter, offset from corneal ablation center, and high-order corneal aberrations were observed before and 3mo after surgery. RESULTS: Three months after operation, there was no difference in uncorrected visual acuity, best corrected visual acuity and refractive diopter between the two groups(P>0.05). The ablation center deviation in CV group(0.20±0.13mm)was less than that in VACRP group(0.27±0.14mm, P

BackgroundClinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat are involved in the pathogenesis of human cancer. Here we conducted a systematic review and meta-analysis to examine whether meat mutagens [PhIP, MeIQx, DiMeIQx, total HCA, and B(a)P] present a risk factor for human cancer.MethodsWe searched the following databases for relevant articles published from inception to 10 Oct 2021 with no language restrictions: Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Baidu Academic, Zhejiang Digital Library. Two independent researchers screened all titles and obtained eligible texts for further screening. Independent data extraction was conducted, and meta-analysis was carried out using random-effects models to calculate the risk ratio of the meat mutagens exposure.ResultsA total of 1,786,410 participants and 70,653 cancer cases were identified. Among these, there were 12 different types of cancer at various sites, i.e., breast, bladder, colorectal, colon, rectum, prostate, lung, Non-Hodgkin lymphoma, kidney, gastric, esophagus, pancreatic, hepatocellular carcinoma. Cancer risk was significantly increased by intake of PhIP (OR = 1.13;95% CI 1.07–1.21; p < 0.001), MeIQx (OR = 1.14; 95% CI: 1.07–1.21; p < 0.001), DiMeIQx (OR = 1.07; 95% CI: 1.01–1.13; p = 0.013), total HCA (OR = 1.20; 95% CI: 1.03–1.38; p = 0.016), and cancer risk was not significantly increased by intake of B(a)P (OR = 1.04; 95% CI: 0.98–1.10; p = 0.206).ConclusionMeat mutagens of PhIP, MeIQx, DiMeIQx, and total HCA have a positive association with the risk of cancer.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022148856].

BackgroundA few intracranial lesions may present only with positional vertigo which are very easy to misdiagnose as benign paroxysmal positional vertigo (BPPV); the clinicians should pay more attention to this disease.ObjectivesTo analyze the clinical characteristics of 6 patients with intracranial tumors who only presented with positional vertigo to avoid misdiagnosing the disease.Material and methodsSix patients with intracranial tumors who only presented with positional vertigo treated in our clinic between May 2015 to May 2019 were reviewed, and the clinical symptoms, features of nystagmus, imaging presentation, and final diagnosis of the patients were evaluated.ResultsAll patients presented with positional vertigo and positional nystagmus induced by the changes in head position or posture, including one case with downbeating nystagmus in a positional test, two cases with left-beating nystagmus, one case with apogeotropic nystagmus in a roll test, one case with right-beating nystagmus, and one case with left-beating and upbeating nystagmus. Brain MRI showed the regions of the tumors were in the vermis of the cerebellum, the fourth ventricle, the lateral ventricle, and the cerebellar hemisphere.

In view of the presence of pathogenic Vibrio cholerae (V. cholerae) bacteria in environmental waters, including drinking water, which may pose a potential health risk to humans, an ultrasensitive electrochemical DNA biosensor for rapid detection of V. cholerae DNA in the environmental sample was developed. Silica nanospheres were functionalized with 3-aminopropyltriethoxysilane (APTS) for effective immobilization of the capture probe, and gold nanoparticles were used for acceleration of electron transfer to the electrode surface. The aminated capture probe was immobilized onto the Si-Au nanocomposite-modified carbon screen printed electrode (Si-Au-SPE) via an imine covalent bond with glutaraldehyde (GA), which served as the bifunctional cross-linking agent. The targeted DNA sequence of V. cholerae was monitored via a sandwich DNA hybridization strategy with a pair of DNA probes, which included the capture probe and reporter probe that flanked the complementary DNA (cDNA), and evaluated by differential pulse voltammetry (DPV) in the presence of an anthraquninone redox label. Under optimum sandwich hybridization conditions, the voltammetric genosensor could detect the targeted V. cholerae gene from 1.0 × 10−17–1.0 × 10−7 M cDNA with a limit of detection (LOD) of 1.25 × 10−18 M (i.e., 1.1513 × 10−13 µg/µL) and long-term stability of the DNA biosensor up to 55 days. The electrochemical DNA biosensor was capable of giving a reproducible DPV signal with a relative standard deviation (RSD) of n = 5). Satisfactory recoveries of V. cholerae cDNA concentration from different bacterial strains, river water, and cabbage samples were obtained between 96.5% and 101.6% with the proposed DNA sandwich biosensing procedure. The V. cholerae DNA concentrations determined by the sandwich-type electrochemical genosensor in the environmental samples were correlated to the number of bacterial colonies obtained from standard microbiological procedures (bacterial colony count reference method).

miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.

To analyze the seismic response characteristics of unequal-span subway station structures in saturated sites, a three-dimensional numerical model of an unequal-span subway station structure is established, based on the finite element analysis software MIDAS-GTS. The elastic modulus, cohesion, Poisson’s ratio, and friction angle are selected as the sensitivity parameters. Moreover, combined with the saturated two-phase medium dynamic analysis method, the orthogonal test method is also utilized, to obtain the corresponding seismic response range. The results show that, the lower end of the shear wall and the vicinity of the cantilever span are prone to bending failure, and that the central columns are prone to shear failure. Under the action of a horizontal ground motion, or under the combination of horizontal and vertical ground motions, the influence of the elastic modulus is the largest, the influence of the Poisson’s ratio and the friction angle is the second largest, and the influence of cohesion is the smallest. This procedure of seismic response characteristics for unequal-span subway station structures can provide a reference for the seismic design of these structures.

An impedimetric aptasensor based on a polyaniline (PAni) support matrix is developed through the surface modification of a screen-printed carbon electrode (SPE) for aflatoxin B1 (AFB1) detection in foodstuffs and feedstuffs for food safety. The PAni is synthesized with the chemical oxidation method and characterized with potentiostat/galvanostat, FTIR, and UV–vis spectroscopy techniques. The stepwise fabrication procedure of the PAni-based aptasensor is characterized by means of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods. The impedimetric aptasensor is optimized using the EIS technique, and its feasibility of detecting AFB1 in real sample matrices is evaluated via a recovery study in spiked foodstuffs and feedstuffs, such as pistachio nuts, cinnamons, cloves, corn, and soybeans, with a good recovery percentage, ranging from 87.9% to 94.7%. The charge transfer resistance (RCT) at the aptasensor interface increases linearly with the AFB1 concentration in the range of 3 × 10−2 nM to 8 × 10−2 nM, with a regression coefficient (R2) value of 0.9991 and detection limit of 0.01 nM. The proposed aptasensor is highly selective towards AFB1 and partially selective to AFB2 and ochratoxin A (OTA) due to their similar structures that differ only at the carbon–carbon double bond located at C8 and C9 and the large molecule size of OTA.

Abstract Severe combined immunodeficiency (SCID) is a rare genetic condition characterized by significant T cell lymphopenia and impaired T cell function. Many jurisdictions use the quantitation of T cell receptor excision circles (TRECs) to screen for SCID in newborns, but false positives may be seen in several conditions. We report 3 newborns with neonatal abstinence syndrome who presented with decreased TREC copy number.

This article aims to investigate the impact of employee perceptions of corporate social responsibility (CSR) on job embeddedness under the drastic circumstances of coronavirus disease 2019 (COVID-19). This study also investigated the role of organizational identification as a psychological mechanism linking employee perceptions of corporate social responsibility (CSR) to job embeddedness. Survey data were collected from 325 employees in banking industry of China and analyzed using partial least squares structural equation modeling (PLS-SEM). Results revealed that CSR to employees and organizational identification were positively and significantly related to job embeddedness, while CSR to customers, CSR to government, and CSR to society did not significantly predict job embeddedness. Organizational identification fully mediated the relationship between CSR to customers, CSR to government, CSR to society and job embeddedness, and partially mediated the relationship between CSR to employees and job embeddedness. The results suggest engaging in CSR activities can lead employees to identify themselves with the organization and enhance their embeddedness. The article concludes with several implications for practice and recommendations for future research.

This paper uses CiteSpace to visualize and analyze the literature related to agricultural non-point source pollution in China Knowledge Network (CNKI) from 1993~2022. The results showed that the research on agricultural non-point source pollution has gone through three stages: the beginning (1993~2006), booming development (2007~2011), and stable development (2011-2022). The research on agricultural non-point source pollution focuses mainly on agricultural non-point source pollution, pollution control, and model simulation. Agricultural non-point source pollution has always played a leading role in the development of the research field since the research until now, and model simulation and spatial distribution have been continuously cited from the emergence of clustering until now, and are widely available in the research field.

To comprehensively understand the research status and development trend of soil inorganic carbon development, this study comprised 441 inorganic carbon pool papers from 1991-2022 in the Web of Science database based on CiteSpace software, and conducted Visualization analysis to explore the research hotspots, research status and development trend in this field. The results show that number of publications has increased year by year, and the clustering results show that the research topics mainly involve terrestrial biosphere, coastal forest ecosystem, forest soil, changed temperature hutrient. The hotspots of research include the blue carbon, soil carbon sequestration and dissolution processes of inorganic carbon. In addition, development trend include the effects of land use change, temperature, organic matter and other changes. soil inorganic carbon sinks, carbon dioxide uptake and the application of isotope technology are the ongoing concerns in this field, which will be the hotspot of soil inorganic carbon sink research in the future period.

To explore the correlation between Fried Frailty Phenotype (FFP) and the muscle thickness and quality of local muscle, and to provide a reasonable basis for the application of ultrasound measurement in the frailty assessment. A total of 150 people (age ≥ 65 years, 58 women, 92 men) were included from the First Hospital Affiliated to Nanjing Medical University. They were divided into Normal group (40 cases), Prefrailty group (69 cases) and Frailty group (41 cases). The thickness and the quality of local muscle were detected by ultrasound. Participants in the prefrailty group had a higher grayscale value of the vastus lateralis muscle, indicating the deterioration of muscle quality. At the frailty stage, the muscle thickness and quality of the vastus lateralis muscle and the anterior tibialis muscle decreased significantly compared with the normal and the prefrailty group. Pearson's correlation analysis also showed FFP was negatively correlated with muscle thickness and quality of the lower limbs. In multiple regression model, FFP was positively associated with gray value (Vastus lateralis muscle:β =0.457, p < 0.001; Anterior tibialis muscle: β = 0.220, p = 0.037) and inversely associated with muscle thickness (Vastus lateralis muscle:β = −0.973, p = 0.031; Anterior tibialis muscle: β = −4.551, p = 0.004) in the frailty stage. Together, FFP was closely related to muscle thickness and quality, especially vastus lateralis muscle. Moreover, Muscle quality has deteriorated in the prefrailty stage, which is earlier than muscle thickness.

Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.

Abstract Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

Abstract Background Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy. Methodology We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients’ microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy. Results Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health. Conclusion Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

Based on localized surface plasmon resonance (LSPR) enhanced quantum dot (QD) emission in a sandwich assay of “capture PCT antibody/PCT/detection PCT antibody labelled with QD” on a gold nanoarray chip, a fully automated point-of-care (POC) system for quick quantitative analysis of procalcitonin (PCT) for sepsis diagnostics was developed. The core technology of the system is to design and fabricate gold nanostructures that can generate plasmonics at resonant wavelength coincident with excitation wavelength of the fluorescent dyes. Gold nanopillar arrays at the size of 140 nm square and 320 nm pitch were found to be good candidates for the desired dye emission. Gold nanochip fabricated by e-beam lithography or nanoimprinting was integrated into a microfluidic chip, with analyte sampling and bioassay reagent flow controlled by LabVIEW program. To detect QD emission of the bioassay from the chip, a CCD camera and a laser source controlled by LabVIEW were incorporated to form a user-friendly and fully-automated POC system for on-site detection of PCT in clinics. Upon detection, the microfluidic chip is inserted into the POC system, where the processes of blood sample loading, detection antibody recognition, fluorescent dye labelling, fluorescent detection, and data analysis are conducted automatically in the device within 30 min at a test sensitivity of 0.5 ng/ml, which fulfills the clinical needs for diagnosis of sepsis through PCT biomarker.

Summary: Human mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency. : This study highlights a novel strategy to improve cartilage repair using hMSCs cultured with heparan sulfates that target and stabilize fibroblast growth factor 2. The work is focused on developing bio-additives that prevent the loss of hMSCs stemness during their ex vivo expansion that is important for maintaining their therapeutic utility. Keywords: heparan sulfate, stemness, potency, ex vivo expansion, FGF2, efficacy, osteochondral regeneration, cartilage repair

Abstract Background Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55–199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours. Methods This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours. Results Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. Conclusions Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS.

Background: Dianbaizhu (Gaultheria leucocarpa var. yunnanensis), a traditional Chinese/ethnic medicine (TC/EM), has been used to treat rheumatoid arthritis (RA) for a long time. The anti–rheumatic arthritis fraction (ARF) of G. yunnanensis has significant anti-inflammatory and analgesic activities and is mainly composed of methyl salicylate glycosides, flavonoids, organic acids, and others. The effective ingredients and rudimentary mechanism of ARF remedying RA have not been elucidated to date.Purpose: The aim of the present study is to give an insight into the effective components and mechanisms of Dianbaizhu in ameliorating RA, based on the estimation of the absorption, distribution, metabolism, and excretion (ADME) properties, analysis of network pharmacology, and in vivo and in vitro validations.Study design and methods: The IL-1β–induced human fibroblast-like synoviocytes of RA (HFLS-RA) model and adjuvant-induced arthritis in the rat model were adopted to assess the anti-RA effect of ARF. The components in ARF were identified by using UHPLC-LTQ-Orbitrap-MSn. The quantitative structure–activity relationship (QSAR) models were developed by using five machine learning algorithms, alone or in combination with genetic algorithms for predicting the ADME properties of ARF. The molecular networks and pathways presumably referring to the therapy of ARF on RA were yielded by using common databases and visible software, and the experimental validations of the key targets conducted in vitro.Results: ARF effectively relieved RA in vivo and in vitro. The five optimized QSAR models that were developed showed robustness and predictive ability. The characterized 48 components in ARF had good biological potency. Four key signaling pathways were obtained, which were related to both cytokine signaling and cell immune response. ARF suppressed IL-1β–induced expression of EGFR, MMP 9, IL2, MAPK14, and KDR in the HFLS-RA .Conclusions: ARF has good druggability and high exploitation potential. Methyl salicylate glycosides and flavonoids play essential roles in attuning RA. ARF may partially attenuate RA by regulating the expression of multi-targets in the inflammation–immune system. These provide valuable information to rationalize ARF and other TC/EMs in the treatment of RA.