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Markov boundary (MB) has been widely studied in single-target scenarios. Relatively few works focus on the MB discovery for variable set due to the complex variable relationships, where an MB variable might contain predictive information about several targets. This paper investigates the multi-target MB discovery, aiming to distinguish the common MB variables (shared by multiple targets) and the target-specific MB variables (associated with single targets). Considering the multiplicity of MB, the relation between common MB variables and equivalent information is studied. We find that common MB variables are determined by equivalent information through different mechanisms, which is relevant to the existence of the target correlation. Based on the analysis of these mechanisms, we propose a multi-target MB discovery algorithm to identify these two types of variables, whose variant also achieves superiority and interpretability in feature selection tasks. Extensive experiments demonstrate the efficacy of these contributions.

Objective: To explore the clinicopathological features of solitary fibrous tumors (SFTs) of the lung. Methods: We collected the clinical data of 52 patients with SFTs of the lung confirmed by pathology, and summarized the clinical, radiological, and morphological features, the immunophenotypes, and the prognosis of SFTs. Results: Fifty-two cases of SFTs of the lung were enrolled in this study, including 51 cases of borderline and 1 case of malignancy, 22 males and 30 females. The average onset age was 52.7 years. The lower lobe of the left lung was the preferred site of SFTs, accounting for 30.77% (16/52). Chest CT showed regular and well-demarcated soft tissue density mass, and the tumor size of most cases (46/52, 88.46%) was 1–10 cm. Morphological features: The distribution of tumor cells showed sparse and dense areas. Tumor cells were spindle-shaped, in whorls or hemangiopericytoma-like conformation. Atypia, mitotic figures, and necrosis were found. Immunohistochemistry showed positive expression of CD34, STAT6, Vimentin, BCL2, and CD99. Ki-67 was ≤ 5% in borderline SFTs and >20% in a malignant SFT. Conclusions: Solitary fibrous tumors of the lung occur more frequently in middle-aged and elderly people, and there is no significant difference in gender. The lower lobe of the left lung is the preferred site of SFTs. The size of most SFTs is 1–10 cm. Chest CT shows morphologically regular and well-demarcated soft tissue density mass. Pathologically, SFTs of the lung are mostly borderline and occasionally malignant. Immunohistochemistry shows the positive expression of CD34, STAT6, Vimentin, BCL2, and CD99.

Immune checkpoint inhibitors (ICIs) achieve a milestone in cancer treatment. Despite the great success of ICI, ICI therapy still faces a big challenge due to heterogeneity of tumor, and therapeutic response is complicated by possible immune-related adverse events (irAEs). Therefore, it is critical to assess the systemic immune response elicited by ICI therapy to guide subsequent treatment regimens. Positron emission tomography (PET) molecular imaging is an optimal approach in cancer diagnosis, treatment effect evaluation, follow-up, and prognosis prediction. PET imaging can monitor metabolic changes of immunocytes and specifically identify immuno-biomarkers to reflect systemic immune responses. Here, we briefly review the application of PET molecular imaging to date of systemic immune responses following ICI therapy and the associated rationale.

The introduction of MXene improves hydrophobic properties and enhance the hydrophobic encapsulation effect of a hydrogel. It can effectively prevent the influence of external moisture on the hydrogel, enabling outstanding sensing stability performance in harsh environments.

The aim of the study is to investigate the diagnostic accuracy of radiomics on iodine maps from dual-energy computed tomography (DECT) in distinguishing lung cancer from benign pulmonary nodules.This retrospective study was approved by the institutional review board, and written informed consent was waived. A total of 109 patients with 55 malignant nodules and 62 benign nodules underwent contrast-enhanced DECT. Eight iodine uptake parameters on iodine maps generated by DECT were calculated and established a predictive model. Eighty-seven radiomics features of entire tumor were extracted from iodine maps and established a radiomics model. The iodine uptake model and radiomics model were independently built based on the highly reproducible features using the least absolute shrinkage and selection operator method. The diagnostic accuracy of 2 models were assessed using receiver operating curve analysis. For external validation, 47 patients (25 benign and 22 malignant) from another hospital were assigned to testing data set.All iodine uptake features showed significant association with malignancy ( P0.01) and 2 selected features (mean value of virtual noncontrast images and mean value of vital part on contrast-enhanced image) constituted the iodine model. The radiomics model comprised 2 features (original shape sphericity and original glszm small area high gray level emphasis), which showed good discrimination both in the training cohort (area under the curve, 0.957) and validation cohort (area under the curve, 0.800). Radiomics model showed superior performance than iodine uptake model (accuracy, 89.7% vs 80.6%).Radiomics model extracted from iodine maps provided a robust diagnostic tool for discriminating pulmonary malignant nodules and had high potential in clinical application.

In this paper, we introduce Gene Knockout Inference (GenKI), a virtual knockout (KO) tool for gene function prediction using single-cell RNA sequencing (scRNA-seq) data in the absence of KO samples when only wild-type (WT) samples are available. Without using any information from real KO samples, GenKI is designed to capture shifting patterns in gene regulation caused by the KO perturbation in an unsupervised manner and provide a robust and scalable framework for gene function studies. To achieve this goal, GenKI adapts a variational graph autoencoder (VGAE) model to learn latent representations of genes and interactions between genes from the input WT scRNA-seq data and a derived single-cell gene regulatory network (scGRN). The virtual KO data is then generated by computationally removing all edges of the KO gene—the gene to be knocked out for functional study—from the scGRN. The differences between WT and virtual KO data are discerned by using their corresponding latent parameters derived from the trained VGAE model. Our simulations show that GenKI accurately approximates the perturbation profiles upon gene KO and outperforms the state-of-the-art under a series of evaluation conditions. Using publicly available scRNA-seq data sets, we demonstrate that GenKI recapitulates discoveries of real-animal KO experiments and accurately predicts cell type-specific functions of KO genes. Thus, GenKI provides an in-silico alternative to KO experiments that may partially replace the need for genetically modified animals or other genetically perturbed systems.

We revealed that the profile of the urinary tract microbiota in RA featured with increased microbial richness and shifted taxa, associated with immunological and metabolic changes of the disease, underlining the interplay between urinary microbiota and host autoimmunity.

Background The plant hormone auxin is widely involved in plant growth, development, and morphogenesis, and the TIR1/AFB and AUX/IAA proteins are closely linked to rapid auxin response and signal transmission. However, their evolutionary history, historical patterns of expansion and contraction, and changes in interaction relationships are still unknown. Results Here, we analyzed the gene duplications, interactions, and expression patterns of TIR1/AFBs and AUX/IAAs to understand their underlying mechanisms of evolution. The ratios of TIR1/AFBs to AUX/IAAs range from 4:2 in Physcomitrium patens to 6:29 in Arabidopsis thaliana and 3:16 in Fragaria vesca. Whole-genome duplication (WGD) and tandem duplication have contributed to the expansion of the AUX/IAA gene family, but numerous TIR1/AFB gene duplicates were lost after WGD. We further analyzed the expression profiles of TIR1/AFBs and AUX/IAAs in different tissue parts of Physcomitrium patens, Selaginella moellendorffii, Arabidopsis thaliana and Fragaria vesca, and found that TIR1/AFBs and AUX/IAAs were highly expressed in all tissues in P. patens, S. moellendorffii. In A. thaliana and F. vesca, TIR1/AFBs maintained the same expression pattern as the ancient plants with high expression in all tissue parts, while AUX/IAAs appeared tissue-specific expression. In F. vesca, 11 AUX/IAAs interacted with TIR1/AFBs with different interaction strengths, and the functional specificity of AUX/IAAs was related to their ability to bind TIR1/AFBs, thus promoting the development of specific higher plant organs. Verification of the interactions among TIR1/AFBs and AUX/IAAs in Marchantia polymorpha and F. vesca also showed that the regulation of AUX/IAA members by TIR1/AFBs became more refined over the course of plant evolution. Conclusions Our results indicate that specific interactions and specific gene expression patterns both contributed to the functional diversification of TIR1/AFBs and AUX/IAAs.

Cell-surface proteins play a critical role in cell function and are primary targets for therapeutics. CITE-seq is a single-cell technique that enables simultaneous measurement of gene and surface protein expression. It is powerful but costly and technically challenging. Computational methods have been developed to predict surface protein expression using gene expression information such as from single-cell RNA sequencing (scRNA-seq) data. Existing methods however are computationally demanding and lack the interpretability to reveal underlying biological processes. We propose CrossmodalNet, an interpretable machine learning model, to predict surface protein expression from scRNA-seq data. Our model with a customized adaptive loss accurately predicts surface protein abundances. When samples from multiple time points are given, our model encodes temporal information into an easy-to-interpret time embedding to make prediction in a time point-specific manner able to uncover noise-free causal gene-protein relationships. Using two publicly available time-resolved CITE-seq data sets, we validate the performance of our model by comparing it to benchmarking methods and evaluate its interpretability. Together, we show our method accurately and interpretably profiles surface protein expression using scRNA-seq data, thereby expanding the capacity of CITE-seq experiments for investigating molecular mechanisms involving surface proteins.

Objective. Evaluate the effectiveness of extracellular vesicles derived from mesenchymal stem cells (MSCs) in the treatment of chronic kidney disease based on meta-analysis. Methods. We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science and other databases on randomized controlled trial (RCT) of oral traditional Chinese patent medicines and simple preparations to improve inflammatory response in patients with diabetes nephropathy. The search time was from the establishment of the database to October 2022. All researchers independently screened and extracted documents for quality evaluation. Data analysis was conducted on documents that met quality standards using Stata 16.0 software and RevMan 5.4. Results. 12 studies (n=198) satisfied the inclusion criteria.The results demonstrated that the levels of Scr (SMD=-0.38;95%CI=-4.29,-1.87;PPPPP=0.003) and the apoptotic cells (SMD=-3.85%, 95%CI=-5.05, -2.65;P＜0.00001) were significantly decreased in the EV group. Conclusion. The results confirmed that MSCs-EV therapy could improve renal function and delaying kidney fibrosis in preclinical animal CKD model.

Background: Thyroid cancer (TC) is a frequent endocrine malignant tumor with various pathologic types. miRNA-363-3p plays a pivotal part in the occurrence, development, prognosis, and treatment of cancer. Objective: To explore the mechanism of miRNA-363-3p in TC and provide a new idea for targeted therapy of TC. Methods: Differential miRNAs and downstream target mRNAs in TC tissues were predicted with bioinformatics analysis. Expression levels of miRNA-363-3p and Synaptotagmin I (SYT1) in TC cells were ascertained by qRT-PCR. Cell migration, invasion, and proliferation were detected by wound healing assay, transwell assay, colony formation assay, CCK-8, and BrdU fluorescence experiment, respectively. Flow cytometry was utilized to detect the levels of apoptosis and necrosis. Immunofluorescence assay was used for detecting autophagosome formation in cells, and the expression levels of autophagy-related proteins, as well as NF-κB related proteins, were measured by western blot. Dual-luciferase reporter gene assay was applied for detecting the interaction between miRNA-363-3p and SYT1. Results: miRNA-363-3p was prominently down-regulated in TC cells. miRNA-363-3p overexpression suppressed migration, invasion, and proliferation, promoting apoptosis and necrosis of TC cells. As the downstream target of miRNA-363-3p, SYT1 was up-regulated in TC cells. SYT1 overexpression reversed the inhibition of TC cell proliferation, invasion, migration, and autophagy mediated by miRNA-363-3p overexpression. In addition, miRNA-363-3p overexpression inhibited the activation of the NF-κB pathway in cells, while further overexpression of SYT1 weakened the inhibition of miRNA-363-3p overexpression on the NF-κB pathway. Conclusion: miRNA-363-3p affected the NF-κB signaling pathway by down-regulating SYT1 expression to inhibit the malignant progression of TC cells, providing theoretical support for the treatment of TC.

Objective: The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer. Methods: A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. Results: Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA), high ApoB/ApoA level indicated a shorter OS (HR:2.028, 95% CI: 1.174-2.504, P = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076-3.009, P = 0.025). Other serum lipid molecules were not associated with PFS and OS. Conclusion: ApoB/ApoA might be an independent prognostic factor of pancreatic cancer.

Background Metastasis is the leading cause of death among patients with colorectal cancer (CRC). Therefore, it is important to explore the molecular mechanisms of metastasis to develop effective therapeutic targets for CRC. In the present study, ribosomal protein L21 (RPL21) was considered as being involved in promoting CRC metastasis, yet the underlying mechanism requires further investigation. Methods Immunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction were performed to measure the expression of RPL21 and lysosome-associated membrane protein 3 (LAMP3) in CRC tissues and cells. Wound healing, transwell migration, and invasion assays were performed to study the migration and invasion of cultured CRC cells. An orthotopic CRC mouse model was developed to investigate the metastatic ability of CRC. Transcriptome sequencing was conducted to identify the genes related to RPL21. The dual-luciferase reporter gene assay was performed to determine the transcriptional activity of transcription factor EB (TFEB). The GST/His pull-down assay was performed to investigate the specific binding sites of RPL21 and LAMP3. The cell adhesion assay was performed to determine the adhesion ability of CRC cells. Immunofluorescence staining was performed to observe focal adhesions (FAs). Results RPL21 was highly expressed in CRC, contributing to tumor invasiveness and poor patient prognosis. Functionally, RPL21 promoted the migration and invasion of CRC cells in vitro and tumor metastasis in vivo. Moreover, LAMP3 was identified as being highly related to RPL21 and was essential in promoting the migration and invasion of CRC cells. Mechanistically, RPL21 activated the transcriptional function of TFEB to upregulate LAMP3 expression. RPL21 directly bound to the aa 341–416 domain of LAMP3 via its aa 1–40 and aa 111–160 segments. The combination of RPL21 and LAMP3 enhanced the stability of the RPL21 protein by suppressing the degradation of the ubiquitin–proteasome system. Furthermore, RPL21 and LAMP3 promoted the formation of immature FAs by activating the FAK/paxillin/ERK signaling pathway. Conclusions RPL21 promoted invasion and metastasis by regulating FA formation in a LAMP3-dependent manner during CRC progression. The interaction between RPL21 and LAMP3 may function as a potential therapeutic target against CRC.

Metabolic syndrome (MS) has become a health concern worldwide. Gut microbiota and metabolites play an important role in human health.

Background To compare all-cause rebleeding rates and mortality after transjugular intrahepatic portosystemic shunt (TIPS) between severe thrombocytopenia (TCP) and non-severe TCP patients admitted for variceal bleeding.Methods Between January 2017 and June 2020, patients with severe TCP (platelets 9/L) who received TIPS procedures for variceal bleeding at three medical centers were included. As controls, non-severe TCP patients were matched (1:1) by age, viral hepatitis, splenectomy, white blood cell, prothrombin time, international normalized ratio, total bilirubin, and acute variceal bleeding. Primary outcome was 6-week all-cause rebleeding. Secondary outcomes included 1-year all-cause rebleeding, 30-day and 1-year all-cause mortality and complications occurred during or after TIPS creation.Results A total of 373 patients were included in the study, with 84 patients in each cohort after matching. All-cause rebleeding rates at 6-week and 1-year post-TIPS were similar in cohorts with severe versus non-severe TCP (6.0% vs 4.8% at 6-week and 10.7% vs 10.7% at 1-year; P = 0.962; HR: 1.023; 95% CI, 0.406–2.577). One-year all-cause mortality was also comparable between the two cohorts (10.7% vs 9.5%, P = 0.754; HR: 1.164; 95% CI, 0.449–3.018). The comparison of 30-day post-TIPS mortality was inconclusive due to the relatively small number of positive outcome events. A trend toward slightly higher major complications was observed in the severe TCP cohort (8.3% vs 2.4%, P = 0.078).Conclusions Compared with non-severe TCP, severe TCP did not increase the risk of early and late rebleeding after TIPS in patients with variceal bleeding.

Supplementary Data from High-Throughput Hacking of the Methylation Patterns in Breast Cancer by In vitro Transcription and Thymidine-Specific Cleavage Mass Array on MALDI-TOF Silico-Chip

Over the last decade, the rapidly expanding interest in the involvement of DNA methylation in developmental mechanisms, human diseases, and malignancies has highlighted the need for an accurate, quantitative, and high-throughput assay. Existing methods are limited and are often too laborious for high-throughput analysis or inadequate for quantitative analysis of methylation. Recently, a MassCLEAVE assay has been developed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to analyze base-specific methylation patterns after bisulfite conversion. To find an efficient and more cost-effective high-throughput method for analyzing the methylation profile in breast cancer, we developed a method that allows for the simultaneous detection of multiple target CpG residues by using thymidine-specific cleavage mass array on matrix-assisted laser desorption/ionization time-of-flight silicon chips. We used this novel quantitative approach for the analysis of DNA methylation patterns of four tumor suppressor genes in 96 breast tissue samples from 48 patients with breast cancer. Each individual contributed a breast cancer specimen and corresponding adjacent normal tissue. We evaluated the accuracy of the approach and implemented critical improvements in experimental design. (Mol Cancer Res 2008;6(11):1702–9)

Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.

Brain iron overload is positively correlated with the pathogenesis of Alzheimer's disease (AD). However, the role of iron in AD pathology is not completely understood. Furin is the first identified mammalian proprotein convertase that catalyzes the proteolytic maturation of large numbers of prohormones and proproteins. The correlation between altered furin expression and AD pathology has been suggested, but the underlying mechanism remains to be clarified. Here, we found that the expression of furin in the hippocampus of Alzheimer's model APP/PS1 mice was significantly reduced, and we demonstrated that the reduction of furin was directly caused by hippocampal iron overload using wild-type mice with intrahippocampal injection of iron. In cultured neuronal cells, this suppression effect was observed as transcriptional inhibition. Regarding the changes of furin-mediated activities caused by hippocampal iron overload, we found that the maturation of brain-derived neurotrophic factor (BDNF) was impeded and the expression levels of synaptogenesis-related proteins were downregulated, leading to cognitive decline. Furthermore, iron chelation or furin overexpression in the hippocampus of APP/PS1 mice increased furin expression, restored synapse plasticity, and ameliorated cognitive decline. Therefore, the inhibitory effect of hippocampal iron accumulation on furin transcription may be an important pathway involved in iron-mediated synapse damage and memory loss in AD. This study provides new insights into the molecular mechanisms of the toxic effects of iron in neurons and AD pathophysiology and renders furin as a potential target for treatment of iron overload-related neurodegenerative diseases.

As a fossil energy with low carbon, natural gas has been regarded as an important energy for the energy green transition in the past few decades. It has long shouldered the mission of improving air quality and slowing climate warming. However, in recent years, with the acceleration of the energy transition, natural gas has become a major source of carbon emissions in Europe, but before the full coverage of renewable energy, natural gas remains the Europe's main energy in the short term. In such a complicated background, what is the short-term outlook for the European Union's (EU) natural gas demand? This paper will answer this question by forecasting the EU's natural gas consumption. A review of the literature that studies on gas consumption forecasting for the Europe has always been for one country or one region; there is no study for all EU countries, and the forecast periods are mostly for hourly, daily and annual data and no studies for monthly data. In order to fill these two research gaps, this paper forecasts the monthly natural gas consumption from 2021 to 2025 of the top seven gas-consuming countries in the EU and obtains the EU's total consumption on this basis. In addition, due to the nonlinear seasonal fluctuations in the monthly consumption data of the countries studied, a novel seasonal forecasting model is proposed to better fit this trend, named nonlinear grey Bernoulli model based on Hodrick-Prescott (HP) filter (HP-NGBM(1,1)). To demonstrate that HP-NGBM(1,1) model has better predictive ability, this paper uses other seasonal models to make comparative forecasts, and the results show that the HP-NGBM(1,1) model has the smallest error. The forecasting results can provide the reference for the EU's natural gas consumption market regulation and the formulation of short-term environmental protection strategies and climate change response plannings.

Background/Objective. Impaired glucose tolerance (IGT) is an intermediate metabolic state between normal and diabetes and shows insulin resistant (IR) which to be linked with mitochondria dysfunction. This study is aimed at investigating whether aerobic exercise increases Mfn2 to promote mitochondrial function and improve glucose tolerance and insulin sensitivity in mice with high-fat diet. Methods. Male C57BL/6J mice were randomly divided into six different experimental groups (8 animals/group): (1) normal group (NOR), (2) normal control group (NC), (3) normal + exercise group (NE), (4) IGT group (IGT), (5) IGT control group (IC), and (6) IGT+ exercise group (IE).The exercise group received aerobic exercise for 8 weeks. After the intervention, a blood glucose meter was used to detect the level of glucose tolerance in the mouse’s abdominal cavity; a biochemical kit was used to detect serum lipid metabolism indicators, malondialdehyde, and superoxide dismutase levels; the ELISA method was used to detect serum insulin and mouse gastrocnemius homogenate LDH, PDH, SDH, and CCO levels. Western blot method was used to detect the protein expression levels of NOX4, PGC-1α, and Mfn2 in the gastrocnemius muscle of mice. Results. (1) Mice with high-fat diet for 30 weeks showed impaired glucose tolerance, insulin resistance, and lipid metabolism disorders. The level of LDH, PDH, SDH, and CCO in the gastrocnemius homogenate of mice was reduced. The expressions of NOX4 protein were significantly upregulated, while the expressions of PGC-1α and Mfn2 proteins were significantly downregulated. (2) 8-week aerobic exercise improved the disorders of glucose and lipid metabolism in IGT mice and increased homogenized LDH, PDH, SDH, and CCO levels, and the expressions of NOX4, PGC-1α, and Mfn2 proteins in the gastrocnemius muscle of mice were reversed. It is speculated that aerobic exercise can accelerate energy metabolism. Conclusion. (1) C57BL/6 mice were fed high fat for 30 weeks and successfully constructed a mouse model of reduced diabetes; the mice with reduced diabetes have impaired glucose tolerance, insulin resistance, and lipid metabolism disorders; (2) 8 weeks of aerobic exercise improve glucose tolerance, reduce glucose tolerance in mice, reduce insulin resistance, improve lipid metabolism disorders, and reduce oxidative stress; (3) 8-week aerobic exercise reduces skeletal muscle NOX4 expression and increases glucose tolerance; reduces the expression of LDH, PDH, SDH, and CCO in mouse skeletal muscle; increases the expression level of mitochondrial fusion protein 2 and PGC-1α; improves glucose tolerance; reduces energy metabolism of mouse skeletal muscle; reduces oxidative stress; and reduces insulin resistance. It is speculated that aerobic exercise can accelerate energy metabolism. This process may involve two aspects: firstly, increase the expression level of oxidative metabolism enzymes and promote the tricarboxylic acid cycle; secondly, increase the expression of Mfn2 and accelerate mitochondria fission or fusion to regulate energy metabolism, thereby reducing oxidative stress and insulin resistance.

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy. This is a 6-year retrospective review of patients with a diagnosis of disseminated deep dermatophytosis seen at a single tertiary care institution. Trichophyton rubrum was isolated in four patients, and T. mentagrophyte complex in one patient. All the dermatophyte isolates can grow at 37 °C. Microscopy of purulence sampling from intact nodules demonstrated abundant septate hyphae, and also isolation from purulence was concordance with skin tissue culture. Ultrasound-guided sampling from non-eroded can yield purulence, and direct microscopy of purulence may facilitate rapid diagnosis of deep dermatophytosis and serve to prevent disease progression and dissemination.

Presence and absence polymorphisms (PAPs) exist extensively and have been investigated in different organisms. However, PAPs have rarely been detected between strawberry species at the genome level. This study identified the presence and absence genes (P/A genes) between wild strawberry species (Fragaria vesca) and octoploid cultivated species (F. × ananassa) under a relatively strict criterion. In total, 333 P/A genes present in the wild strawberry but absent in the cultivated strawberry were detected. Of the P/A genes, 91.89% (306/333) were single genes, and only 8.11% were confirmed as multi-genes. The majority of the identified P/A genes in Fragaria were generated by tandem duplications. The P/A genes were unevenly distributed on the seven chromosomes of woodland strawberry, and they clustered preferentially near the telomeric regions of the chromosomes. The P/A genes tended to encode proteins with domains closely associated with responses to varying ecological factors, such as PPR, Protein kinases (PKs), NB-ARC, F-box and EF-hand domains. This indicated that the P/A genes were associated with coping with biotic and abiotic stresses to improve the adaptability of plants to changing environments.

Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field, and can lead to development of novel therapeutic options. Recent findings A series of biological processes induced by TTFields to exert anti-cancer effects have been identified, and applications of TTFields in oncology have been increasingly reported. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategies, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

Tetradymite-structured chalcogenides, such as Bi2Te3 and Sb2Te3, are quasi-two-dimensional (2D) layered compounds, which are significant thermoelectric materials applied near room temperature. The intercalation of guest species in van der Waals (vdW) gap implemented for tunning properties has attracted much attention in recent years. We attempt to insert Ga atoms in the vdW gap between the Te layers in p-type Bi0.3Sb1.7Te3 (BST) for further improving thermoelectrics. The vdW-related defects (including extrinsic interstitial and intrinsic defects) induced by Ga intercalation can not only modulate the carrier concentration but enhance the texture, thereby yielding excellent electrical properties, which is reflected in the power factor PF ~4.43 mW m-1 K-2. Furthermore, the intercalation of Ga produces multi-scale lattice imperfections such as point defects, Te precipitations, and nanopores, realizing the low lattice thermal conductivity in BST-Ga samples. Ultimately, a peak zT ~1.1 at 373 K is achieved in the BST-1%Ga sample and greatly improved by ~22% compared to the pristine BST. The weak bonding of vdW interlayer interaction can boost the synergistic effect for advancing BST-based or other layered thermoelectrics.

Ischemic stroke is associated with high mortality and morbidity rates worldwide. However, the molecular mechanisms underlying the neuronal damage incurred by stroke victims remain unclear. It has previously been reported that ischemic stroke can induce an increase in the levels of brain iron, which is an important factor of in the associated brain damage. Ferroportin 1 (FPN1), the only known cellular iron export protein, is found in brain microvascular endothelial cells (BMVECs) at the blood-brain barrier, and is considered the gateway for entry of plasma iron into the central nervous system. Despite the connection of brain iron to neuronal damage, the role of BMVECs FPN1 in ischemic stroke remains unexplored. Herein, we conditionally deleted Fpn1 in mouse endothelial cells (ECs), using VE-cadherin-Cre transgenic mice, and explored the impact on brain iron homeostasis after stroke. Our data demonstrated that Fpn1 knockout in ECs decreased the brain iron levels in mice, attenuated the oxidative stress and inflammatory responses after stroke, and inhibited both ferroptosis and apoptosis, ultimately alleviating neurological impairment and decreasing cerebral infarct volume during the acute phase of ischemic stroke. By contrast, we found that Fpn1 knockout in ECs delayed the recovery of neurological function in mice following ischemic stroke. We also found that ECs Fpn1 knockout decreased the brain iron levels after stroke, exacerbated glial cell proliferation, and inhibited neuronal development, indicating that the diminished brain iron levels hindered the repair of neural injury in mice. In conclusion, our findings reveal a dual consequence of FPN1 deficiency in ECs in the development of ischemic stroke. More specifically, iron deficiency initially exerts a neuroprotective effect during the acute phase of ischemic stroke but inhibits recovery during the later stages. Our findings are important to the development of iron- or FPN1-targeting therapeutics for the treatment of ischemic stroke.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P