Combination treatment with interferon-γ may be a potential strategy to improve the efficacy of cytotherapy for rheumatoid arthritis: A network meta-analysis.

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): -0.70; 95% confidence interval (CI): -1.25, -0.15; P = 0.01) and 3rd month (SMD: -1.47; 95% CI: -2.77, -0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: -0.38; 95% CI: -0.72, -0.05; P = 0.03) and 6th months (SMD: -0.81; 95% CI: -1.32, -0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels.

Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study.

BACKGROUND: Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain. METHODS: We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test. RESULTS: The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d-1; IQR, 120-408 mg.d-1), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d-1 at day 1 postimplant (P = .001), to 0 (0-0) mg.d-1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred. CONCLUSIONS: Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Evaluation of the invasiveness of pure ground-glass nodules based on dual-head ResNet technique.

OBJECTIVE: To intelligently evaluate the invasiveness of pure ground-glass nodules with multiple classifications using deep learning. METHODS: pGGNs in 1136 patients were pathologically confirmed as lung precursor lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Four different models [EfficientNet-b0 2D, dual-head ResNet_3D, a 3D model combining three features (3D_3F), and a 3D model combining 19 features (3D_19F)] were constructed to evaluate the invasiveness of pGGNs using the EfficientNet and ResNet networks. The Obuchowski index was used to evaluate the differences in diagnostic efficiency among the four models. RESULTS: The patients with pGGNs (360 men, 776 women; mean age, 54.63 ± 12.36 years) included 235 cases of AAH + AIS, 332 cases of MIA, and 569 cases of IAC. In the validation group, the areas under the curve in detecting the invasiveness of pGGNs as a three-category classification (AAH + AIS, MIA, IAC) were 0.8008, 0.8090, 0.8165, and 0.8158 for EfficientNet-b0 2D, dual-head ResNet_3D, 3D_3F, and 3D_19F, respectively, whereas the accuracies were 0.6422, 0.6158, 0.651, and 0.6364, respectively. The Obuchowski index revealed no significant differences in the diagnostic performance of the four models. CONCLUSIONS: The dual-head ResNet_3D_3F model had the highest diagnostic efficiency for evaluating the invasiveness of pGGNs in the four models.

Conformation-Confined Organic Butterfly-Molecule with High Photoluminescence Efficiency, Deep-Blue Amplified Spontaneous Emission, and Unique Piezochromic Luminescence.

Organic fluorophores with tunable π-conjugated paths have attracted considerable attention owing to their diverse properties and promising applications. Herein, we present a tailored butterfly like molecule, 2,2'-(2,5-bis (2,2-diphenylvinyl)-1,4-phenylene)dinaphtha-lene (BDVPN), which exhibits diverse photophysical features in its two polymorphs. The BP phase crystal, with its "aligned wings" conformation, possesses emissive characteristics that are nearly identical to those in dilute solutions. In contrast, the BN phase crystal, which adopts an "orthogonal wings" conformation, exhibits an unusual hypsochromic-shifted emission compared to its dilute solution counterparts. This intriguing hypsochromic-shifted emission originates from the reduction in the effective conjugated length of the molecular skeleton. Notably, BN phase crystals also exhibit exceptional optical performance, featuring high-efficiency emission (76.6%), low-loss optical waveguides (0.571 dB mm-1), deep-blue amplified spontaneous emission (ASE) with a narrow full width at half maximum (FWHM: 6.4 nm), and a unique 200 nm bathochromic shift of piezochromic luminescence.

Salviapenghuana (Lamiaceae), a new species from Guizhou, China.

Salviapenghuana, a new species from Guizhou Province of southwestern China, is described and illustrated. Morphologically, Salviapenghuana is similar to S.filicifolia, but can be easily distinguished from the latter by ovate-lanceolate bracts, purple corolla, and foot-shaped fused lower arms of connective. In addition, S.penhuana is morphologically similar to S.cavaleriei, but differs by having 3-4-pinnate leave, ovate-lanceolate bracts, puberulent calyx, and longer upper arms of connective. Based on the fibril root, small calyx and corolla, and completely reduced posterior thecae, S.penghuana should be placed in section Sobiso of subg. Glutinaria.

Solid State Additive Manufacturing of Thermoset Composites.

Softening and subsequent deformation are significant challenges in additive manufacturing of thermal-curable thermosets. This study proposes an approach to address these issues, involving the preparation of thermosetting composite powders with distinct curing temperatures, the utilization of cold spray additive manufacturing (CSAM) for sample fabrication, and the implementation of stepwise curing for each component. To validate the feasibility of this approach, two single-component thermosetting powders P1 and P2 and their composite powder C were subjected to CSAM and stepwise curing. From the sample morphology observation and deposition/curing mechanism investigation based on thermomechanical analysis and differential scanning calorimetry, it is found that severe plastic deformation occurs during the CSAM process, accompanied by heat generation, leading to local melting to promote a good bond at the contact surface of the particles and form small pores. During the progressive curing, the samples printed using C demonstrate superior deformation resistance compared with those using P1 and P2, and the curing time is reduced from 16.7 h to 1.5 h, due to the sequential curing reactions of P1 and P2 components in composite C, allowing the uncured P2 and cured P1 to alternately remain solid for providing structural support and minimizing deformation.

Characterization of Lomofungin Gene Cluster Enables the Biosynthesis of Related Phenazine Derivatives.

Phenazine-based small molecules are nitrogen-containing heterocyclic compounds with diverse bioactivities and electron transfer properties that exhibit promising applications in pharmaceutical and electrochemical industries. However, the biosynthetic mechanism of highly substituted natural phenazines remains poorly understood. In this study, we report the direct cloning and heterologous expression of the lomofungin biosynthetic gene cluster (BGC) from Streptomyces lomondensis S015. Reconstruction and overexpression of the BGCs in Streptomyces coelicolor M1152 resulted in eight phenazine derivatives including two novel hybrid phenazine metabolites, and the biosynthetic pathway of lomofungin was proposed. Furthermore, gene deletion suggested that NAD(P)H-dependent oxidoreductase gene lomo14 is a nonessential gene in the biosynthesis of lomofungin. Cytotoxicity evaluation of the isolated phenazines and lomofungin was performed. Specifically, lomofungin shows substantial inhibition against two human cancer cells, HCT116 and 5637. These results provide insights into the biosynthetic mechanism of lomofungin, which will be useful for the directed biosynthesis of natural phenazine derivatives.

The modified exhaust method is used in open-heart surgery for cardiopulmonary bypass in children with congenital heart disease.

Objective: This study aimed to assess the efficacy of a modified exhaust method in pediatric open-heart surgery involving cardiopulmonary bypass. Method: Data from 303 cases conducted at the Department of Cardiac Surgery, Guizhou Hospital, Shanghai Children's Medical Center, between October 2023 and March 2024 were analyzed. Among these cases, 202 utilized the modified exhaust method, divided into group A (101 cases with median thoracotomy) and group C (101 cases with lateral thoracotomy), while 101 cases used the traditional exhaust method in group B (median thoracotomy). Comparative analysis included general patient data, cardiopulmonary bypass duration, aortic cross-clamp time, time for exhaust and reperfusion upon opening, post-reperfusion ST segment abnormalities on electrocardiogram, intracardiac pneumogram observations via esophageal ultrasound, relevant plasma biochemical indexes on postoperative day one, postoperative drainage volume, duration of ventilator use, and length of stay in the intensive care unit (ICU). Results: There was no difference in between-group comparisons regarding age (27.98 ± 3.57 vs. 34.05 ± 3.96 months; P = 0.401) and weight (12.23 ± 0.55vs. 12.59 ± 0.70 Kg; P = 0.563). Longer Cardiopulmonary bypass times were observed in patients undergoing median thoracotomy than those undergoing lateral thoracotomy (group B: 108.47 ± 2.30 min vs. group C: 117.03 ± 2.82 min, P = 0.002; group A: 108.91 ± 2.63 min vs. group C: 117.03 ± 2.82 min, P = 0.035). Exhaust and rebound times after opening were significantly shorter in the modified exhaust-method group compared with the traditional-method group (Group A: 52.62 ± 1.39 s vs. Group B: 65.20 ± 1.49 s, P < 0.001; Group B: 65.20 ± 1.49 s vs. Group C: 4.31 ± 1.16 s, P < 0.001). There was no statistical difference in terms of postoperative biochemical indexes, drainage volume, ventilator use time, and ICU stay time (all P > 0.05). Conclusions: The modified exhaust method demonstrates overall good immediate results in pediatric congenital heart surgery. It was superior to the traditional exhaust method in terms of reducing exhaust times and potentially minimizing the risk of local aortic injuries. Additionally, it appeared to be suitable for lateral thoracotomy surgery.

Age-Disturbed Vascular Extracellular Matrix Links to Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a common but life-threatening vascular condition in men at an advanced age. However, the underlying mechanisms of age-increased incidence and mortality of AAA remain elusive. Here, we performed RNA sequencing (RNA-seq) of mouse aortas from males (young: 3-month, n = 4 vs old: 23-month, n = 4) and integrated with the data sets of human aortas (young: 20-39, n = 47 vs old: 60-79 years, n = 92) from GTEx project and the data set (GSE183464) for AAA to search for age-shifted aortic aneurysm genes, their relevant biological processes, and signaling pathways. Angiotensin II-induced AAA in mice was used to verify the critical findings. We found 1 001 genes transcriptionally changed with ages in both mouse and human. Most age-increased genes were enriched intracellularly and the relevant biological processes included mitochondrial function and translational controls, whereas the age-decreased genes were largely localized in extracellular regions and cell periphery and the involved biological processes were associated with extracellular matrix (ECM). Fifty-one were known genes for AAA and found dominantly in extracellular region. The common age-shifted vascular genes and known aortic aneurysm genes had shared functional influences on ECM organization, apoptosis, and angiogenesis. Aorta with angiotensin II-induced AAA exhibited similar phenotypic changes in ECM to that in old mice. Together, we present a conserved transcriptional signature for aortic aging and provide evidence that mitochondrial dysfunction and the imbalanced ribosomal homeostasis act likely as driven-forces for aortic aging and age-disturbed ECM is the substrate for developing AAA.

Distinct neural pathway and its information flow for blind individual's Braille reading.

Natural Braille reading presents significant challenges to the brain networks of late blind individuals, yet its underlying neural mechanisms remain largely unexplored. Using natural Braille texts in behavioral assessments and functional MRI, we sought to pinpoint the neural pathway and information flow crucial for Braille reading performance in late blind individuals. In the resting state, we discovered a unique neural connection between the higher-order 'visual' cortex, the lateral occipital cortex (LOC), and the inferior frontal cortex (IFC) in late blind individuals, but not in sighted controls. The left-lateralized LOC-IFC connectivity was correlated with individual Braille reading proficiency. Prolonged Braille reading practice led to increased strength of this connectivity. During a natural Braille reading task, bidirectional information flow between the LOC and the IFC was positively modulated, with a predominantly stronger top-down modulation from the IFC to the LOC. This stronger top-down modulation contributed to higher Braille reading proficiency. We thus proposed a two-predictor multiple regression model to predict individual Braille reading proficiency, incorporating both static connectivity and dynamic top-down communication between the LOC-IFC link. This work highlights the dual contributions of the occipito-frontal neural pathway and top-down cognitive strategy to superior natural Braille reading performance, offering guidance for training late blind individuals.

Activation of α7 nicotinic acetylcholine receptors inhibits hepatic necroptosis and ameliorates acute liver injury in mice.

BACKGROUND: Acute liver injury (ALI) is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate ALI and investigate its possible mechanisms. METHODS: ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type (WT), α7nAChR knockout (α7nAChR -/-) and Sting mutation (Stinggt/gt) mice in the presence or absence of a pharmacological selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis and infiltration of immune cells during ALI were assessed. RESULTS: The expression of α7nAChR in liver tissue was increased in LPS/D-Gal induced ALI mice. Compared to the age-matched WT mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacological activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86 hiCD163low), Ly6Chi monocytes (CD45+CD11b+MHCⅡ lowLy6C hi), but increased the resident Kupffer cells (CD45+CD11bintF4/80 hiTIM4 hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR. CONCLUSIONS: Our study revealed that activating α7nAChR could protect against LPS/D-Gal induced ALI by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway.

Comparative analysis of visual-thermal perceptions and emotional responses in outdoor open spaces: Impacts of look-up vs. look-forward viewing perspectives.

Horizontal and vertical viewing perspectives exert varying influences on the environmental perceptions and emotional states of college students. Despite this, scant research addresses the impact on this demographic. We selected typical campus open spaces for comprehensive physical parameter assessments, encompassing meteorological and spatial characteristics. A cohort of 36 healthy college students participated in a questionnaire survey designed to ascertain shifts in visual comfort, thermal comfort, and emotional responses when viewing landscapes in look-forward and look-up orientations. Key findings following both viewing modalities included: 1) a notable rise in mean visual comfort vote (MVCV), by 1.22 for look-forward and 1.01 for look-up, with a pronouncedly higher sunlight sensation vote (SSV) for the latter orientation; 2) a significant increase in thermal comfort vote (TCV), although the difference in increments between the two viewing angles was minimal; 3) Positive affect (PA) exhibited considerable improvement in both viewing conditions, while negative affect (NA) was markedly reduced in the look-up condition relative to look-forward viewing; 4) The SSV was predominantly influenced by the trunk ratio and canopy-to-trunk ratio, with substantial weights of 31.47% and 32.15%, respectively. Landscape element diversity emerged as the most critical factor affecting visual comfort vote (VCV) and aesthetic assessment score (AAS), with overwhelming weights of 70.67% and 63.15%, respectively. Moreover, the leaf ratio was identified as the chief determinant of emotional responses. Our results provide insights into the design of campus spaces for enhanced student well-being.

Existence of Blastocystis infection in bar-headed goose (Anser indicus).

Blastocystis is a common intestinal protist in humans and animals. Currently, Blastocystis infection in bar-headed geese is unknown. To understand the prevalence and distribution of Blastocystis subtypes in bar-headed geese, fecal samples were collected from 358 bar-headed geese in three regions. The total infection rate of Blastocystis in bar-headed in China was 5.9% (21/358), with 5.0% (6/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 11.8% (14/119) in Maqu county, Gansu province, and 0.8% (1/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rates by region were statistically significant. Sequences analyses showed that one known subtype (ST7, n = 16) and one potentially novel ST (n = 5) in bar-headed geese were detected in this study. This is the first report on the prevalence and subtype distribution of Blastocystis in bar-headed geese, which will improve our understanding of the epidemiology and public health implications of Blastocystis infection in wild migratory birds.

Machine learning analysis of serum cholesterol's impact on knee osteoarthritis progression.

The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K-L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

Performance of Activities of Daily Living in Typically Developing Children in Korea: Normative Value of K-MBI.

OBJECTIVE: To determine the normative values of the Korean version of the Modified Barthel Index (K-MBI) score for typically developing children in Korea and assess its suitability for use in children. METHODS: Rehabilitation physicians and occupational therapists with children were invited through an online platform to participate in a survey assessing their children's performance of activity of daily living (ADL) using the K-MBI. The questionnaire encompassed queries on sociodemographic information of children and the assessment criteria outlined in the K-MBI. The standardized K-MBI scores by age were estimated using the nonlinear least squares method. RESULTS: The analysis incorporated responses from a total of 206 individuals. K-MBI total scores showed a rapid increase over the first 8 years of life, with 99% of children achieving a score of 90 or higher by age 8. Mobility scores exhibited a swift increase during early childhood, surpassing 90% of the maximum score at 3 years of age and nearing 100% at 7 years of age. In contrast, self-care scores demonstrated a more gradual advancement, achieving approximately 100% of the maximum score by the age of 10 years. CONCLUSION: Age-specific normative values for K-MBI scores of typically developing children were established, which can be used as a reference in clinical care. While the K-MBI captured the overall trajectory of children's ADL development, it did not discern subtle differences across various developmental stages. There is a need for the development of more refined assessment tools tailored specifically to children.

Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.

Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.

Help-Seeking Situations Related to Visual Interactions on Mobile Platforms and Recommended Designs for Blind and Visually Impaired Users.

While it is common for blind and visually impaired (BVI) users to use mobile devices to search for information, little research has explored the accessibility issues they encounter in their interactions with information retrieval systems, in particular digital libraries (DLs). This study represents one of the most comprehensive research projects, investigating accessibility issues, especially help-seeking situations BVI users face in their DL search processes. One hundred and twenty BVI users were recruited to search for information in six DLs on four types of mobile devices (iPhone, iPad, Android phone, and Android tablet), and multiple data collection methods were employed: questionnaires, think-aloud protocols, transaction logs, and interviews. This paper reports part of a large-scale study, including the categories of help-seeking situations BVI users face in their interactions with DLs, focusing on seven types of help-seeking situations related to visual interactions on mobile platforms: difficulty finding a toggle-based search feature, difficulty understanding a video feature, difficulty navigating items on paginated sections, difficulty distinguishing collection labels from thumbnails, difficulty recognizing the content of images, difficulty recognizing the content of graphs, and difficulty interacting with multilayered windows. Moreover, corresponding design recommendations are also proposed: placing meaningful labels for icon-based features in an easy-to-access location, offering intuitive and informative video descriptions for video players, providing structure information about a paginated section, separating collection/item titles from thumbnail descriptions, incorporating artificial intelligence image/graph recognition mechanisms, and limiting screen reader interactions to active windows. Additionally, the limitations of the study and future research are discussed.

The ASB@HNTs-PVA nanofiber membrane, possessing both anti-inflammatory and hemostatic activities, promotes the healing of T2D skin wounds.

The healing of diabetic wounds has long been a significant challenge in the field of medicine. The elevated sugar levels surrounding diabetic wounds create a conducive environment for harmful bacterial growth, resulting in purulent infections that impede the healing process. Thus, the development of a biomaterial that can enhance the healing of diabetic wounds holds great importance. This study developed electrospun dressings for wound healing by combining traditional Chinese medicine and clay. The study utilized electrospinning technology to prepare polyvinyl alcohol (PVA) nanofiber membranes containing ASB and HNTs. These ASB@HNTs-PVA nanofiber membranes demonstrated rapid hemostasis, along with antibacterial and anti-inflammatory properties, facilitating the recovery of type 2 diabetic (T2D) wounds. Various analyses were conducted to assess the performance of the composite nanofiber membrane, including investigations into its biocompatibility and hemostatic abilities through antibacterial experiments, cell experiments, and mouse liver tail bleeding experiments. Western blot analysis confirmed that the composite nanofiber membrane could decrease the levels of inflammatory factors IL-1ß and TNF-α. A type 2 diabetic mouse model was utilized, with wounds artificially induced on the backs of mice. Application of the nanofiber membrane to the wounds further confirmed its anti-inflammatory effects and ability to enhance wound healing in vivo.

The role of Fusobacterium nucleatum in the pathogenesis of colon cancer.

Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.

Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.