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Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Abstract Background Pulmonary embolism (PE) is life-threatening and requires timely and accurate diagnosis, yet current imaging methods, like computed tomography pulmonary angiography, present limitations, particularly for patients with contraindications to iodinated contrast agents. We aimed to develop a quantitative texture analysis pipeline using machine learning (ML) based on non-contrast thoracic computed tomography (CT) scans to discover intensity and textural features correlated with regional lung perfusion (Q) physiology and pathology and synthesize voxel-wise Q surrogates to assist in PE diagnosis. Methods We retrospectively collected 99mTc-labeled macroaggregated albumin Q-SPECT/CT scans from patients suspected of PE, including an internal dataset of 76 patients (64 for training, 12 for testing) and an external testing dataset of 49 patients. Quantitative CT features were extracted from segmented lung subregions and underwent a two-stage feature selection pipeline. The prior-knowledge-driven preselection stage screened for robust and non-redundant perfusion-correlated features, while the data-driven selection stage further filtered features by fitting ML models for classification. The final classification model, trained with the highest-performing PE-associated feature combination, was evaluated in the testing cohorts based on the Area Under the Curve (AUC) for subregion-level predictability. The voxel-wise Q surrogate was then synthesized using the final selected feature maps (FMs) and model score maps (MSMs) to investigate spatial distributions. The Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used to assess the spatial consistency between FMs or MSMs and Q-SPECT scans. Results The optimal model performance achieved an AUC of 0.863 during internal testing and 0.828 on the external testing cohort. The model identified a combination containing 14 intensity and textural features that were non-redundant, robust, and capable of distinguishing between high- and low-functional lung regions. Spatial consistency assessment in the internal testing cohort showed moderate-to-high agreement between MSMs and reference Q-SPECT scans, with median SCC of 0.66, median DSCs of 0.86 and 0.64 for high- and low-functional regions, respectively. Conclusions This study validated the feasibility of using quantitative texture analysis and a data-driven ML pipeline to generate voxel-wise lung perfusion surrogates, providing a radiation-free, widely accessible alternative to functional lung imaging in managing pulmonary vascular diseases. Clinical trial number Not applicable.

Abstract Background Animal and human health are seriously threatened by bacterial infections, which can lead to bacteremia and extremely high rates of morbidity and mortality. Recently, there have been reports indicating the involvement of exosomal circular RNAs (circRNAs) in a range of human disorders and tumor types. However, the role of exosomal circRNAs in bacterial infection remains elusive. Methods We extracted and identified exosomes from the culture medium of PIEC cells infected with or without Glaesserella parasuis. RNA sequencing analysis was performed on the exosomes to screen and identify circRNAs (circHIF1α) associated with Glaesserella parasuis infection. PIEC cells were infected with Staphylococcus aureus or Streptococcus suis 2 to further determine whether exosome-derived circHIF1α was the crucial circHIF1α associated with bacterial infections. The transmission process of exosomes and their circHIF1α between cells was clarified via exosome tracing and co-culture assay. Moreover, the mechanism of circHIF1α being packaged into exosomes was explored, and the effects of exosomes and their circHIF1α on cell proliferation, DNA damage and cell cycle were analyzed. In addition, the binding mode and site of interacting proteins with circHIF1α were further determined. In vivo and in vitro, the role of exosomes and their circHIF1α in host resistance to bacterial infection was confirmed. Results We first discovered a new circHIF1α that was very stable and detectable, encapsulated into exosomes by hnRNPA2B1, and whose expression in exosomes of bacterially infected PIEC cells significantly decreased. Additionally, exosomal circHIF1α reduced bacterial infection both in vitro and in vivo and suppressed the growth of reception cells. Mechanistically, the circHIF1α interacted with the KH domain of IGF2BP3 in an m6A-modified manner, which mediated DNA damage to arrest the cells at the G1/S phase through the interaction between the regulator of Chromosome Condensation 2 (RCC2) and γ-H2AX protein. Exosomal circHIF1α is a unique therapeutic target for bacterial infection since this work highlights its critical function in fighting bacterial infection.

Abstract Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins, which are crucial for dentinogenesis. Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1 (Creb3l1) was specifically enriched in the terminal differentiated odontoblasts. In this study, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells (mDPCs), the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation, protein biosynthesis and transport, all of which were evidenced by a diminished ability of odontoblastic differentiation, a significant reduction in intracellular proteins, and an even greater decline in extracellular supernatant proteins. Dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp), and transmembrane protein 30B (Tmem30b) were identified as direct transcriptional regulatory targets. TMEM30B was intensively expressed in the differentiated odontoblasts, and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro. Deletion of Tmem30b impaired the ability of odontoblastic differentiation, protein synthesis, and protein secretion in mDPCs. Moreover, overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion. Collectively, our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1, Dspp, and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.

Abstract The recent measurement of $$\mathcal {B}(B^+\rightarrow K^+\nu \bar{\nu })$$ B ( B + → K + ν ν ¯ ) by Belle-II reveals a $$2.8~\sigma $$ 2.8 σ deviation from the Standard Model (SM) prediction. Combining this with a prior Belle measurement of $$\mathcal {B}(B^{0}\rightarrow K^{*0}\nu \bar{\nu })$$ B ( B 0 → K ∗ 0 ν ν ¯ ) , the upper bound of the ratio $$\mathcal {B}(B^{0}\rightarrow K^{*0}\nu \bar{\nu })/\mathcal {B}(B^+\rightarrow K^+\nu \bar{\nu })$$ B ( B 0 → K ∗ 0 ν ν ¯ ) / B ( B + → K + ν ν ¯ ) is notably smaller than the SM prediction. In this work, tensions are solved within the framework of Standard Model effective field theory (SMEFT). The flavor-changing-neutral-current (FCNC) and charged-current observables of either down-type ( $$b\rightarrow s\nu \bar{\nu }$$ b → s ν ν ¯ , $$b\rightarrow s\ell ^+\ell ^-$$ b → s ℓ + ℓ - , and $$b\rightarrow u_i\ell \bar{\nu }$$ b → u i ℓ ν ¯ ) or up-type ( $$u_j\rightarrow u_i\nu \bar{\nu }$$ u j → u i ν ν ¯ , $$u_j\rightarrow u_i\ell ^+\ell ^-$$ u j → u i ℓ + ℓ - , and $$u_j\rightarrow s\ell \bar{\nu }$$ u j → s ℓ ν ¯ ) processes, described by low-energy effective field theory (LEFT) operators, are interconnected by a minimal set of four SMEFT operators at the electroweak scale. Subsequently, we obtain the latest ranges of Wilson coefficients for these four operators through a global fit that accommodates flavor anomalies such as $$R_{K^{(*)}}$$ R K ( ∗ ) , $$R_{D^{(*)}}$$ R D ( ∗ ) , and $$\mathcal {B}(B\rightarrow K^{(*)}\nu \bar{\nu })$$ B ( B → K ( ∗ ) ν ν ¯ ) . Our findings reveal that predictions for $$\mathcal {B}(B^+\rightarrow \tau ^+\nu _\tau )$$ B ( B + → τ + ν τ ) and $$\mathcal {B}(D_s^+\rightarrow \tau ^+\nu _\tau )$$ B ( D s + → τ + ν τ ) align well with measured values from Belle and BESIII, based on the fitted coefficients. The predicted branching fraction for $$B^0\rightarrow K^{*0}\nu \bar{\nu }$$ B 0 → K ∗ 0 ν ν ¯ is $$(1.42\pm 0.74)\times 10^{-5}$$ ( 1.42 ± 0.74 ) × 10 - 5 , closely approaching the current experimental upper limit. Anticipation surrounds the rare decay $$B_s\rightarrow \tau ^+ \tau ^-$$ B s → τ + τ - , expected in the near future with a branching fraction on the order of $$10^{-4}$$ 10 - 4 .

Abstract Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa_circ_0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5′ UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy.

Abstract Objective To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023. Methods Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS. Results From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P

Objective The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins. Methods An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs. Results In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test. Conclusion STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.

Abstract Terahertz frequency band (0.1 ~ 10 THz) can provide ultra-high transmitting rates for massive emerging applications. However, due to the radio frequency impairments and limited signal processing property of baseband devices, it is difficult for the current terahertz communication systems to be used in real applications. In this work, we report a 0.22 THz communication system, which can provide 84 Gbps air interface rate over 1.26 kilometers distance. Such a system is underpinned by three breakthroughs, namely, integrating the reported terahertz wireless communication system, redesigning the signal processing in baseband devices, and increasing the cut-off frequency and transmitting power of radio frequency component by parameter optimizing. Being applied to realize the real-time transmission of the uncompressed 8K ultra high-definition video in the 31st International University Sports Federation in Chengdu, China, this work is a leaping advancement to enable terahertz systems from experiment to promising applications.

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

To reduce the losses caused by aging failure of insulation gate bipolar transistor (IGBT), which is the core components of nuclear power plant rod position indicating and rod control (RPC) system. It is necessary to conduct studies on its life prediction. The selection of IGBT failure characteristic parameters in existing research relies heavily on failure principles and expert experience. Moreover, the analysis and learning of time-domain degradation data have not been fully conducted, resulting in low prediction efficiency as the monotonicity, time correlation, and poor anti-interference ability of extracted degradation features. This paper utilizes the advantages of the stacked denoising autoencoder(SDAE) network in adaptive feature extraction and denoising capabilities to perform adaptive feature extraction on IGBT time-domain degradation data; establishes a long-short-term memory (LSTM) prediction model, and optimizes the learning rate, number of nodes in the hidden layer, and number of hidden layers using the Gray Wolf Optimization (GWO) algorithm; conducts verification experiments on the IGBT accelerated aging dataset provided by NASA PCoE Research Center, and selects performance evaluation indicators to compare and analyze the prediction results of the SDAE-LSTM model, PSO-LSTM model, and BP model. The results show that the SDAE-LSTM model can achieve more accurate and stable IGBT life prediction.

AbstractContext Nine steaming and nine drying is a traditional Chinese medicine (TCM) processing method and it is widely used for processing tonifying herbs. Modern research reveals that the repeated steaming and drying process varies the composition and clinical efficacy of TCM.Objective This paper analyzes and explores the historical evolution, research progress, development strategies, and problems encountered in the nine steaming and nine drying process so as to provide a reasonable explanation for this method.Methods English and Chinese literature from 1986 to 2023 was collected from databases including Web of Science, PubMed, Elsevier, Chinese Pharmacopoeia 2020 (CP), and CNKI (Chinese). Nine steaming and nine drying, processing, TCM and pharmacological activity were used as the key words.Results Nine steaming and nine drying has undergone thousands of years of clinical practice. Under specific processing conditions of nine steaming and nine drying, the ingredients of the TCM have significant changes, which in turn altered clinical applications.Conclusions This review provides sufficient evidence to prove the rationality and scientific value of nine steaming and nine drying and puts forward a development direction for future research.

In the wake of the largest-ever recorded outbreak of mpox in terms of magnitude and geographical spread in human history since May 2022, we innovatively developed an automated online sewage virus enrichment and concentration robot for disease tracking. Coupled with an artificial intelligence (AI) model, our research aims to estimate mpox cases based on the concentration of the monkeypox virus (MPXV) in wastewater. Our research has revealed a compelling link between the levels of MPXV in wastewater and the number of clinically confirmed mpox infections, a finding that is reinforced by the ability of our AI prediction model to forecast cases with remarkable precision, capturing 87 % of the data’s variability. However, it is worth noting that this high precision in predictions may be related to the relatively high frequency of data acquisition and the relatively non-mobile isolated environment of the hospital itself. In conclusion, this study represents a significant step forward in our ability to track and respond to mpox outbreaks. It has the potential to revolutionize public health surveillance by utilizing innovative technologies for disease surveillance and prediction.

Abstract In this work, we make a study of the τ − → ωπ − ν τ decay in the framework of low-energy effective field theory. The J P G $$ {J}^{\mathcal{P}G} $$ decompositions of the quark currents and the ωπ final state show that, besides the Standard Model vector interaction, only the non-standard tensor interaction can have a non-zero contribution to the decay. To discuss its effect, a reliable calculation of the ωπ tensor form factors is necessary. After constructing the Lagrangian of resonance chiral theory with external tensor sources, we calculate both the vector and tensor form factors with the relevant resonance couplings determined by combining the QCD short-distance constraints, the fit to the spectral function of τ − → ωπ − ν τ decay, as well as the matching between the O p 4 $$ \mathcal{O}\left({p}^4\right) $$ odd-intrinsic-parity operators after integrating out the vector resonances and the O p 6 $$ \mathcal{O}\left({p}^6\right) $$ operators of chiral perturbation theory. The new physics effect is then investigated in the distributions of the spectral function and the forward-backward asymmetry of τ − → ωπ − ν τ decay. We find that the spectral function is dominated by the Standard Model, and the non-standard tensor contribution is negligible. However, since the forward-backward asymmetry can be only generated with a non-zero tensor interaction, the observable is quite sensitive to this kind of new physics. A future measurement of the observable at the Belle II experiment as well as at the proposed Tera-Z and STCF facilities is, therefore, strongly called for to check the existence of such a non-standard tensor interaction.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract Purpose Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. Methods We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. Results In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. Conclusions Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Abstract Background The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. Methods We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. Results We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. Conclusion We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K–AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

ABSTRACT Aims/Introduction Diabetes has been related to an increased risk of oral cancer. Nevertheless, the impact of diabetes on the outcome of individuals with oral and oropharyngeal cancer is not clear. In this study, a meta‐analysis was carried out to assess the link between diabetes and the survival of individuals with oral and oropharyngeal cancer. Materials and Methods Relevant cohort studies for the meta‐analysis objective were obtained through searching electronic databases, such as PubMed, Web of Science and Embase. The data were combined using a random effects model that accounted for differences between studies. Results A total of 10 cohorts involving 21,871 patients with oral and oropharyngeal cancer were included. Pooled results suggest that compared with those with normoglycemia, oral and oropharyngeal cancer patients with diabetes were associated with a poor overall survival (hazard ratio 1.69, 95% confidence interval 1.29–2.22, P 0.05). In addition, diabetes was also associated with a poor progression‐free survival of patients with oral and oropharyngeal cancer (hazard ratio 1.61, 95% confidence interval 1.30–1.99, P

Abstract Background Overt gastrointestinal bleeding (GIB) is a potentially serious and life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, relatively little information is available regarding overt GIB in children. Objectives To assess the prevalence, clinical patterns, and outcomes of overt GIB in children undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods A total of 123 consecutive patients with malignant or non-malignant blood disorders who received haplo-HSCT were reviewed in our hospital between October 2017 and October 2022. Overt GIB was determined as hematemesis, melena or hematochezia. Continuous variables were compared by Mann Whitney U test. Categorical parameters were compared by the χ2 test or Fisher’s exact test. Kaplan-Meier curves and log-rank tests were used to assess overall survival (OS), non-relapse mortality (NRM) and relapse. Univariate and multivariate analyses were performed to identify potential risk factors of overt GIB development. Results The median follow-up was 26.3 (range,1.7–74.8) months. Overt GIB occurred in 31 patients (25.2% incidence), with a median time elapsed after haplo-HSCT of 376 days (range, 58–1275 days). Compared with the non-GIB group, patients with overt GIB had reduced OS and increased NRM. In multivariate analysis, grade III–IV gut acute graft versus-host disease (aGvHD), thrombotic microangiopathy (TMA) and cytomegalovirus (CMV) viremia were significant risk factors for the occurrence of overt GIB after haplo-HSCT. Conclusions Overt GIB is a frequent complication after haplo-HSCT in pediatric patients, and associated with worse survival. Grade III–IV gut aGvHD, TMA and CMV viremia were associated with its development.

Objective There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

Abstract Background Today, the detection rate of lung nodules is increasing. Some of these nodules may become malignant. Thus, timely resection of potentially malignant nodules is essential. However, Identifying the location of nonsurface or soft-textured nodules during surgery is challenging. Various localization techniques have been developed to accurately identify lung nodules. Common methods include preoperative CT-guided percutaneous placement of hook wires and microcoils. Nonetheless, these procedures may cause complications such as pneumothorax and haemothorax. Other methods regarding localization of pulmonary nodules have their own drawbacks. We conducted a clinical study which was retrospective to identify a safe, accurate and suitable method for determining lung nodule localization. To evaluate the clinical value of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization in thoracoscopic lung nodule resection. Methods We retrospectively collected the clinical data of 120 patients who underwent lung nodule localization and resection surgery at the Department of Thoracic Surgery, First Affiliated Hospital of Bengbu Medical College, from January 2020 to January 2022. Among them, 30 patients underwent CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization, 30 patients underwent only CT-assisted body surface localization, 30 patients underwent only intraoperative stereotactic anatomical localization, and 30 patients underwent CT-guided percutaneous microcoil localization. The success rates, complication rates, and localization times of the four lung nodule localization methods were statistically analysed. Results The success rates of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization and CT-guided percutaneous microcoil localization were both 96.7%, which were significantly higher than the 70.0% success rate in the CT-assisted body surface localization group (P

Abstract The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Abstract Background Prior research has highlighted the involvement of a transcriptional complex comprising C-terminal binding protein 2 (CtBP2), histone acetyltransferase p300, and nuclear factor kappa B (NF-κB) in the transactivation of proinflammatory cytokine genes, contributing to inflammation in mice with acute respiratory distress syndrome (ARDS). Nonetheless, it remains uncertain whether the therapeutic targeting of the CtBP2-p300-NF-κB complex holds potential for ARDS suppression. Methods An ARDS mouse model was established using lipopolysaccharide (LPS) exposure. RNA-Sequencing (RNA-Seq) was performed on ARDS mice and LPS-treated cells with CtBP2, p300, and p65 knockdown. Small molecules inhibiting the CtBP2-p300 interaction were identified through AlphaScreen. Gene and protein expression levels were quantified using RT-qPCR and immunoblots. Tissue damage was assessed via histological staining. Key findings We elucidated the specific role of the CtBP2-p300-NF-κB complex in proinflammatory gene regulation. RNA-seq analysis in LPS-challenged ARDS mice and LPS-treated CtBP2-knockdown (CtBP2KD), p300KD, and p65KD cells revealed its significant impact on proinflammatory genes with minimal effects on other NF-κB targets. Commercial inhibitors for CtBP2, p300, or NF-κB exhibited moderate cytotoxicity in vitro and in vivo, affecting both proinflammatory genes and other targets. We identified a potent inhibitor, PNSC928, for the CtBP2-p300 interaction using AlphaScreen. PNSC928 treatment hindered the assembly of the CtBP2-p300-NF-κB complex, substantially downregulating proinflammatory cytokine gene expression without observable cytotoxicity in normal cells. In vivo administration of PNSC928 significantly reduced CtBP2-driven proinflammatory gene expression in ARDS mice, alleviating inflammation and lung injury, ultimately improving ARDS prognosis. Conclusion Our results position PNSC928 as a promising therapeutic candidate to specifically target the CtBP2-p300 interaction and mitigate inflammation in ARDS management.

Abstract Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

Abstract Background The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. Methods A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. Results A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P

Abstract The generation of alkyl radical from C(sp3)−H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp3)−H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N − H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration. The practical value of this protocol is further demonstrated by the gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives.

Abstract Background Schizochytrium sp. is commercially used for production of docosahexaenoic acid (DHA). Schizochytrium sp. utilizes the polyketide synthase complex (PKS) and a single type I fatty acid synthase (FAS) to synthesize polyunsaturated fatty acids and saturated fatty acids, respectively. The acyl carrier protein (ACP) domains of FAS or PKS are used to load acyl groups during fatty acids biosynthesis. Phosphopantetheinyl transferase (PPTase) transfers the pantetheine moiety from Coenzyme A to the conserved serine residue of an inactive ACP domain to produce its active form. Results In this study, in order to improve production and content of DHA, we decreased the expression of fas, strengthened the expression of the PKS pathway, and enhanced the supply of active ACP in Schizochytrium sp. ATCC20888. Weakening the expression of fas or disruption of orfA both led to growth defect and reduction of lipid yields in the resulting strains WFAS and DPKSA, indicating that both FAS and PKS were indispensable for growth and lipid accumulation. Although WFAS had a higher DHA content in total fatty acids than the wild-type strain (WT), its growth defect and low DHA yield hinders its use for DHA production. Overexpression of the orfAB, orfC, orfC-DH (truncated orfC), or ppt promoted DHA and lipid production, respectively. The yields and contents of DHA were further increased by combined overexpression of these genes. Highest values of DHA yield (7.2 g/L) and DHA content (40.6%) were achieved in a recombinant OPKSABC-PPT, ⁓56.5% and 15.3% higher than the WT values, respectively. Conclusions This study demonstrates that genetic engineering of the fatty acid biosynthetic pathways provides a new strategy to enhance DHA production in Schizochytrium.

Abstract Three-dimensional (3D) glass chips are promising waveguide platforms for building hybrid 3D photonic circuits due to their 3D topological capabilities, large transparent windows, and low coupling dispersion. At present, the key challenge in scaling down a benchtop optical system to a glass chip is the lack of precise methods for controlling the mode field and optical coupling of 3D waveguide circuits. Here, we propose an overlap-controlled multi-scan (OCMS) method based on laser-direct lithography that allows customizing the refractive index profile of 3D waveguides with high spatial precision in a variety of glasses. On the basis of this method, we achieve variable mode-field distribution, robust and broadband coupling, and thereby demonstrate dispersionless LP21-mode conversion of supercontinuum pulses with the largest deviation of

Abtract: Evidence-based guidelines suggest that High-Intensity Interval Training (HIIT) is more beneficial than aerobic exercise for patients with cardiovascular disease, but the differences in underlying pathophysiological mechanisms require further confirmation. The comparison between HIIT and Moderate-Intensity Continuous Training (MICT) in regulating vascular dysfunction in spontaneously hypertensive rats (SHR), along with their underlying mechanisms, has not been previously reported. The purpose of this study is to provide an experimental basis for exercise prescription therapy in hypertensive patients. In this study, six-week-old male SHR were randomly assigned to a HIIT group, MICT group, or sedentary group. Wistar Kyoto rats (WKY) of the same age were used as the control group. The weight, heart rate, and blood pressure of the rats were monitored weekly throughout twelve weeks of treadmill training. At the end of the protocol, serum and aortic vascular tissues were collected for further vascular function tests and molecular and biochemical analyses. The results show that MICT is more favorable for weight control than HIIT, while both forms of exercise offer equal protection against hypertension. However, MICT demonstrates a greater benefit in preserving vascular morphology, whereas HIIT is more effective in reducing oxidative stress. Both HIIT and MICT ameliorate vascular dysfunction in SHR by suppressing nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 3 (NLRP3)-induced pyroptosis. The superior effect of HIIT on vascular dysfunction may be related to the inhibition of oxidative stress injury through AMPKα-SIRT1 activation. This study provides insight into the dose-effect relationship of exercise for cardiovascular health and offers foundational evidence for the development of exercise prescription therapies.

Oysters, particularly Portuguese oyster (Crassostrea angulata), are highly valued for their nutritional and flavor qualities, making them important in global aquaculture. Triploid oysters have gained attention for maintaining higher meat quality year-round compared to diploids, but there is limited research on how ploidy affects their biochemical and flavor profiles. This study uses a non-targeted metabolomics approach, including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), to investigate flavor substance differences between triploid and diploid C. angulata. A total of 13 volatile compounds were identified in diploid oysters, while 28 were found in triploids. Significant upregulation of inosine, guanosine, L-aspartic acid, and taurine in triploids contributes to their enhanced flavor profile. Additionally, triploids showed higher nicotinamide concentrations, while diploids had increased 25-hydroxycholesterol. These findings highlight the advantages of triploid oysters in aquaculture for improved flavor and nutrition, supporting their potential for year-round production.

Reducing the oral bioavailability of metal contaminants including As, Cd, , and Pb in foods can protect human health. Studies showed reduced metal bioavailability with elevated Ca and Fe intake; however, the effectiveness of enhancing food Ca and Fe bioavailability remains unknown. Based on a mouse bioassay and using metal accumulation in mouse tissues (kidneys and liver) as the bioavailability endpoint, this study investigated the roles of casein phosphopeptides (CPP, food nutrition fortifier) in lowering the As, Cd, and Pb bioavailability from consuming a metal-contaminated wheat. The CPP amendment at 0.10–0.50% in wheat promoted its Ca bioavailability, causing 33–62% and 59–80% decreases in the gene expression encoding for duodenal Ca and phosphate transporters in mice. This limited transcellular transport of Cd2+ and inorganic arsenate via Ca and phosphate transporters respectively, thus leading to 27% and 34% decreases in Cd and As contents in mouse kidneys fed with wheat at 0.50% CPP amendment. In addition, CPP promoted the colonization of Feacalibaculum and Bifidobacterium in mouse gut, likely promoting As excretion in feces by 81–112%. In contrast to As, and Cd, CPP failed to reduce Pb contents in mouse tissue after consuming CPP-amended wheat, probably by elevating wheat-Pb solubility in the intestinal fluid by 48–136%. However, co-amendment of 0.30% CPP and 500 ​μg ​g−1 Ca as Ca gluconate lowered the As, Cd, and Pb contents in mouse kidneys by 38–71%. The data indicate that fortifying Ca together with CPP in wheat can reduce human exposure to multi-metals via dietary intake.

Abstract Real‐time polymerase chain reaction (RT‐PCR) remains the most prevalent molecular detection technology for sewage analysis but is plagued with numerous disadvantages, such as time consumption, high manpower requirements, and susceptibility to false negatives. In this study, an automated robot‐driven photoelectrochemical (PEC) biosensing platform is constructed, that utilizes the CRISPR/Cas12a system to achieve fast, ultrasensitive, high specificity detection of biological loads in sewage. The Shennong‐1 robot integrates several functional modules, involving sewage sampling and pretreatment to streamline the sewage monitoring. A screen‐printed electrode is employed with a vertical graphene‐based working electrode and enhanced with surface‐deposited Au nanoparticles (NPs). CdTe/ZnS quantum dots (QDs) are further fabricated through the double‐stranded DNA (dsDNA) anchored on Au NPs. Using the cDNA template of Omicron BA.5 spike gene as a model, the PEC biosensor demonstrates excellent analytical performance, with a lower detection limit of 2.93 × 102 zm and an outstanding selectivity at the level of single‐base mutation recognition. Furthermore, the rapid, accurate detection of BA.5 in sewage demonstrates the feasibility of the PEC platform for sewage monitoring. In conclusion, this platform allows early detection and tracking of infectious disease outbreaks, providing timely data support for public health institutions to take appropriate prevention and control measures.

Active fault zones are critical pathways for the migration of deep fluids to the Earth’s surface, carrying gases such as He, Rn, and CO2 that provide evidence for the physical and chemical dynamics of the Earth’s interior. This review examines the geochemical characteristics of fault zone gases and their implications for understanding fault activity and seismic events. Fault zones with high activity levels exhibit significant gas release, and variations in soil and hot spring gas concentrations can serve as indicators of seismic activity. Changes in gas concentrations and isotopic ratios, particularly before and after earthquakes, reflect the dynamic interplay between deep-sourced and shallow-sourced fluids. Seismic-induced stress alterations enhance gas release along fault zones, leading to observable anomalies that can aid in earthquake monitoring and prediction. The study underscores the importance of isotope tracing in deciphering fluid sources, migration pathways, and the evolution of fault zones, providing valuable information for assessing tectonic activity and mitigating seismic risks.

As a new class of robots, soft continuum manipulators have attracted attention due to their flexibility and compliance. However, these characteristics create challenges for precise modeling and control. This study proposes a hybrid offline and online data‐driven scheme to achieve high‐precision tracking control of a soft continuum manipulator. First, a novel multiscale deep neural network learns the manipulator model offline. Specifically, the feature fusion module extracts highly discriminative features and captures long‐term dependencies from the temporal trajectory data. The self‐attention module strengthens the ability to represent fusion features and enhances the model prediction accuracy. Then, the learnt model is updated using multisensor data online, and the proposed controller further compensates for the updated model and enhances the tracking accuracy in the movement stage. Finally, the experimental results demonstrate a significant improvement in motion accuracy under different trajectory‐tracking scenarios (i.e., deviations of

Abstract BackgroundThe increasing demand for personal health record (PHR) systems is driven by individuals’ desire to actively manage their health care. However, the limited functionality of current PHR systems has affected users’ willingness to adopt them, leading to lower-than-expected usage rates. The HL7 (Health Level Seven) PHR System Functional Model (PHR-S FM) was proposed to address this issue, outlining all possible functionalities in PHR systems. Although the PHR-S FM provides a comprehensive theoretical framework, its practical effectiveness and applicability have not been fully explored. ObjectiveThis study aimed to design and develop a tethered PHR prototype in accordance with the guidelines of the PHR-S FM. It sought to explore the feasibility of applying the PHR-S FM in PHR systems by comparing the prototype with the results of previous research. MethodsThe PHR-S FM profile was defined to meet broad clinical data management requirements based on previous research. We designed and developed a PHR prototype as a web application using the Fast Healthcare Interoperability Resources R4 (FHIR) and Logical Observation Identifiers Names and Codes (LOINC) coding system for interoperability and data consistency. We validated the prototype using the Synthea dataset, which provided realistic synthetic medical records. In addition, we compared the results produced by the prototype with those of previous studies to evaluate the feasibility and implementation of the PHR-S FM framework. ResultsThe PHR prototype was developed based on the PHR-S FM profile. We verified its functionality by demonstrating its ability to synchronize data with the FHIR server, effectively managing and displaying various health data types. Validation using the Synthea dataset confirmed the prototype’s accuracy, achieving 100% coverage across 1157 data items. A comparison with the findings of previous studies indicated the feasibility of implementing the PHR-S FM and highlighted areas for future research and improvements. ConclusionsThe results of this study offer valuable insights into the potential for practical application and broad adoption of the PHR-S FM in real-world health care settings.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Chromium, being among the most toxic heavy metals, continues to demand immediate attention in the remediation of Cr-contaminated environments. In this study, a strain of LBA36 (Bacillus toyonensis) was isolated from heavy metal contaminated soil in Luanchuan County, Luoyang City, China. The reduction and adsorption rates of LBA36 in 30 mg·L−1 Cr-containing medium were 97.95% and 8.8%, respectively. The reduction mechanism was confirmed by Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy (XPS). Cr(VI) reduction by this strain predominantly occurred outside the cell, with hydroxyl, amide, carboxyl, C-N group, carbonyl, and sulfur carbonyl as the main reaction sites. XPS analysis revealed the presence of Cr2p1/2 and Cr2p3/2. Furthermore, the hydroponic experiment showed that the fresh weight and plant height of radish seedlings increased by 87.87% and 37.07%, respectively, after inoculation with LBA36 strain under 7 mg·L−1 Cr(VI) stress. The levels of chlorophyll, total protein, malondialdehyde, superoxide dismutase and catalase were also affected to different degrees. In conclusion, this study demonstrated the potential of microbial and phytoremediation in the treatment of heavy metal toxicity, and laid the foundation for the development of effective bioremediation methods for Cr(VI) pollution.

ObjectiveTo compare the effects of robot-assisted therapy with conventional therapy for accelerating stratified intervention in poststroke patients with upper limb dysfunction.BackgroundFor stroke survivors, recovery of upper extremity function remains a major challenge in rehabilitation. Literature has suggested that the rate of recovery may improve if treatments can be individualized to their clinical profiles. However, there still lack clinical evidence on how to create treatment tailored to individual patients. Robot-assisted Therapy (RT) provides a straightforward approach to adjustment of the assistance-resistance continuum for individual patients. In early Brunnstrom stages of recovery, patients benefit from assistance training, whereas in later stages the training is favored with resistance. Therefore, RT may enhance Conventional Therapy (CT) but the use of RT in stratified intervention has not been investigated. This study evaluated the possible benefit of adopting RT following a protocol of upper-limb training, which was stratified with the Brunnstrom stage of each individual.MethodsThis study was a single-blinded randomized controlled trial. A total of 53 patients with stroke were recruited and randomized into 2 groups (CT, n = 27, 3 dropped out and RT, n = 26, 2 dropped out). Both groups were trained once per day, 5 days per week for 4 weeks. The CT group received 30 min of conventional therapy; the RT group received 30 min of upper limb robot-assisted training. Patients were assessed at the beginning, week-2, and week-4 of the treatment. The outcome measures included the Fugl-Meyer Assessment Upper-Extremity (FMA-UE) and the Modified Barthel Index (MBI).ResultsAcross the 4-week intervention, participants in the RT group recovered 1.979 points of FMA-UE per week, compared to 1.198 points per week in the CT group (t94 = 3.333, p

Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4+CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.