Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.

Synergistic effects of oral inoculation with a recombinant Lactobacillus plantarum NC8 strain co-expressing interleukin-2 and interleukin-17B on the efficacy of the infectious bronchitis vaccine in chickens.

Mucosal vaccination strategies are easier to implement than others in large-scale poultry farming. However, the adjuvants that are approved for veterinary use, which are predominantly aluminum- and oil-emulsion-based adjuvants, are not suitable for mucosal vaccination and carry a risk of adverse reactions. In this study, we engineered a novel Lactobacillus plantarum NC8 strain that co-expresses chicken interleukin-2 (IL-2) and IL-17B, which we designated NC8-ChIL2-17B, and evaluated its potential as an oral immunoadjuvant. The immunomodulatory properties of NC8-ChIL2-17B were evidenced by its ability to activate macrophages and inhibit the proliferation of infectious bronchitis virus (IBV) in vitro. We then confirmed its immunoadjuvant activity in vivo by orally administering NC8-ChIL2-17B along with a commercial IBV vaccine to chicks. The results indicated that NC8-ChIL2-17B enhanced the immune response elicited by the IBV vaccine and increased the levels of IBV-specific IgG and sIgA antibodies produced in response to IBV infection. Additionally, administration of NC8-ChIL2-17B promoted weight gain and beneficially modulated the gut microbiota, resulting in improved chicken performance. These findings suggest that oral administration of NC8-ChIL2-17B is a promising strategy to enhance the immune efficacy of the IBV vaccine in chickens, offering an efficacious alternative adjuvant.

Development and evaluation of immunological effects of a DNA vaccine encoding phosphoketolase family protein against Nocardia seriolae in hybrid snakehead.

Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata ♀ × Channa argus ♂), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1ß, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.

Association between tea, coffee and caffeine consumption and risk of female infertility: a cross-sectional study.

OBJECTIVES: To explore the association between tea, coffee, and caffeine consumption and the risk of female infertility. METHODS: We analyzed data from 2099 females aged 18 to 44 years, participating in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. We used generalized linear models (GLM) and generalized additive model (GAM) to investigate the dose-response relationship between the tea, coffee, and caffeine consumption and infertility, adjusting for potential confounders. RESULTS: A non-linear relationship was detected between tea consumption and infertility and the inflection point was 2 cups/day. On the right side of the inflection point, we did not detect a significant association. However, on the left side, we found a negative relationship between tea consumption and infertility (OR: 0.73; 95% CI: 0.57 to 0.93; P = 0.0122). Meanwhile, our study found no significant association between coffee (0.96, 0.81 to 1.13, P = 0.6189) or caffeine consumption (1.15, 0.93 to 1.42, P = 0.2148) and female infertility. CONCLUSIONS: Tea consumption was non-linearly associated with infertility, whereas no significant associations were found between coffee, caffeine consumption and infertility.

Association between bedtime and female infertility: a secondary analysis from a cross-sectional study.

Objective: To evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age. Methods: We conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration. Results: After adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25-30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014). Conclusion: Bedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.

Impact of intelligent convolutional neural network -based algorithms on head computed tomography evaluation and comprehensive rehabilitation acupuncture therapy for patients with cerebral infarction.

This work was to evaluate the impacts of comprehensive rehabilitation acupuncture therapy on the recovery of neurological function in cerebral infarction (CI) patients and to utilize convolutional neural network (CNN) intelligent algorithms to optimize head computed tomography (CT) images and improve lesion localization accuracy. 98 CI patients were divided into a control group (Ctrl group) and an experimental group (Exp group), with 48 patients in each group. The patients in the Ctrl group received CT evaluation combined with comprehensive rehabilitation acupuncture therapy. While, those in the Exp group received CT evaluation with the use of CNN algorithms for optimization, along with comprehensive rehabilitation acupuncture therapy. Acupuncture therapy included selecting acupoints on the patient's head, selecting two horizontal needling needles from top to bottom at the acupoints on the front side of the lesion, and then horizontal needling along the top midline. The differences in treatment outcomes were compared between the two groups based on Fugl-Meyer upper limb assessment (FMA) scores, Barthel Index (BI) scores, National Institutes of Health Stroke Scale (NIHSS4) scores, Modified Edinburgh-Scandinavian Stroke Scale (MESSS) scores, and hemodynamics. Simultaneously, the CT images were optimized using CNN intelligent algorithms to improve image quality and lesion localization accuracy. The results showed that the CI CT images processed by the CNN-based intelligent algorithm showed significant improvements in clarity and contrast compared to conventional CT images. The CNN-based intelligent algorithm demonstrated higher sensitivity (97.5 %, 93.8 %), higher PSNR (30.14 dB, 24.72 dB), and lower missed detection rate (0.52 %, 1.88 %) in detecting CI lesions. The total effective rate in the Exp group was 95.83 %, which was significantly higher than the 85.42 % in the Ctrl group (P < 0.05). The Exp group showed significantly higher levels in FMA and BI scores (P < 0.05). After treatment, the NIHSS4 and MESSS scores in the Exp group were lower than those in the Ctrl group (P < 0.05). Additionally, post-treatment, the plasma concentrations and whole-blood viscosity (low shear and high shear) in the Exp group were lower than those in the Ctrl group, and the plasma concentration and whole-blood viscosity (high shear) were also lower than those in the Ctrl group (P < 0.05). In conclusion, comprehensive rehabilitation acupuncture therapy had a positive impact on the recovery of neurological function in CI patients. By applying CNN-based intelligent algorithms to optimize head CT images, lesion localization accuracy can be improved, thereby guiding rehabilitation treatment more effectively.

3D Conjugated Hole Transporting Materials for Efficient and Stable Perovskite Solar Cells and Modules.

The orthogonal structure of the widely used hole transporting material (HTM) 2,2',7,7'-tetrakis(N, N-di-p-methoxyphenylamino)-9,9'-spirobifluorene (Spiro-OMeTAD) imparts isotropic conductivity and excellent film-forming capability. However, inherently weak intra- and inter-molecular π-π interactions result in low intrinsic hole mobility. Herein, a novel HTM, termed FTPE-ST, with a twist conjugated dibenzo(g,p)chrysene core and coplanar 3,4-ethylenedioxythiophene (EDOT) as extended donor units, is designed to enhance π-π interactions, without compromising on solubility. The three-dimensional (3D) configuration provides the material multi-direction charge transport as well as excellent solubility even in 2-methylanisole, and its large conjugated backbone endows the HTM with a high hole mobility. Moreover, the sulfur donors in EDOT units coordinate with lead ions on the perovskite surface, leading to stronger interfacial interactions and the suppression of defects at the perovskite/HTM interface. As a result, perovskite solar cells (PSCs) employing FTPE-ST achieve a champion power conversion efficiency (PCE) of 25.21% with excellent long-time stability, one of the highest PCEs for non-spiro HTMs in n-i-p PSCs. In addition, the excellent film-forming capacity of the HTM enables the fabrication of FTPE-ST-based large-scale PSCs (1.0 cm2) and modules (29.0 cm2), which achieve PCEs of 24.21% (certificated 24.17%) and 21.27%, respectively.

Detection of fucosylated extracellular vesicles miR-4732-5p related to diagnosis of early lung adenocarcinoma by the electrochemical biosensor.

Our preliminary investigation has identified the potential of serum fucosylated extracellular vesicles (EVs) miR-4732-5p in the early diagnosis of lung adenocarcinoma (LUAD) by a fucose-captured strategy utilizing lentil lectin (LCA)-magnetic beads and subsequent screening of high throughput sequencing and validation of real-time quantitative polymerase chain reaction (RT-qPCR). Considering the relatively complicated procedure, expensive equipment, and stringent laboratory condition, we have constructed an electrochemical biosensor assay for the detection of miR-4732-5p. miR-4732-5p is extremely low in serum, down to the fM level, so it needs to be detected by highly sensitive electrochemical methods based on the Mg2+-dependent DNAzyme splitting nucleic acid lock (NAL) cycle and hybridization chain reaction (HCR) signal amplification. In this study, signal amplification is achieved through the dual amplification reactions using NAL cycle in combination with HCR. In addition, hybridized DNA strands bind to a large number of methylene blue (MB) molecules to enhance signaling. Based on the above strategy, we further enhance our signal amplification strategies to improve detection sensitivity and accuracy. The implementation of this assay proceeded as follows: initially, miR-4732-5p was combined with NAL, and then Mg2+-dependent DNAzyme splitted NAL to release auxiliary DNA (S1) strands, which were subsequently captured by the immobilized capture probe DNA (C1) strands on the electrode surface. Following this, abundant quantities of DNA1 (H1) and DNA2 (H2) tandems were generated by HCR, and S1 strands then hybridized with the H1 and H2 tandems through base complementary pairing. Finally, MB was bonded to the H1 and H2 tandems through π-π stacking interaction, leading to the generation of a signal current upon the detection of a potential capable of inducing a redox change of MB by the electrode. Furthermore, we evaluated the performance of our developed electrochemical biosensor assay. The results demonstrated that our assay is a reliable approach, characterized by its high sensitivity (with a detection limit of 2.6 × 10-17 M), excellent specificity, good accuracy, reproducibility, and stability. Additionally, it is cost-effective, requires simple operation, and is portable, making it suitable for the detection of serum fucosylated extracellular vesicles miR-4732-5p. Ultimately, this development has the potential to enhance the diagnostic efficiency for patients with early-stage LUAD.

Effects of physical activity on infertility in reproductive females.

OBJECTIVES: To explore the relationship between different types of physical activity and female infertility. METHODS: This study analyzed data from 2,796 female participants aged 18-44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors. RESULTS: We found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008). CONCLUSIONS: The relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.

Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression.

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. RESULTS: We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. CONCLUSIONS: NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

A Multifunctional Dye Molecule as the Interfacial Layer for Perovskite Solar Cells.

In perovskite solar cells (PSCs), defects in the interface and mismatched energy levels can damage the device performance. Improving the interface quality is an effective way to achieve efficient and stable PSCs. In this work, a multifunctional dye molecule, named ThPCyAc, was designed and synthesized to be introduced in the perovskite/HTM interface. On one hand, various functional groups on the acceptor unit can act as Lewis base to reduce defect density and suppress nonradiative combinations. On the other hand, the stepwise energy-level alignment caused by ThPCyAc decreases the accumulation of interface carriers for facilitating charge extraction and transmission. Therefore, based on the ThPCyAc molecule, the devices exhibit elevated open-circuit voltage and fill factor, resulting in the best power conversion efficiency (PCE) of 23.16%, outperforming the control sample lacking the interface layer (PCE = 21.49%). Excitingly, when attempting to apply it as a self-assembled layer in inverted devices, ThPCyAc still exhibits attractive behavior. It is worth noting that these results indicate that dye molecules have great potential in developing multifunctional interface materials to obtain higher-performance PSCs.

Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy.

Immune checkpoint blockade therapy provides a new strategy for tumor treatment; however, the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects. Herein, we reported a lipid/PLGA nanocomplex (RDCM) co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1MT to improve immunotherapy of colon cancer. Arginine-glycine-aspartic acid (RGD) as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol (PEG), and programmed cell death-ligand 1 (PD-L1) peptide inhibitor DPPA (sequence: CPLGVRGK-GGG-d(NYSKPTDRQYHF)) was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker. The Ce6 and 1MT were encapsulated in PLGA nanoparticles. The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes. When the nanocomplexes were delivered to tumor, DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding. RGD facilitated the cellular internalization of nanocomplexes via avß3 integrin. Strong immunogenic cell death was induced by 1O2 generated from Ce6 irradiation under 660 nm laser. 1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment. The RDCM facilitated the maturation of dendritic cells, inhibited the activity of IDO, and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice, triggering a robust immunological memory effect, thus effectively preventing tumor metastasis. The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.

Dopant-Free Pyrene-Based Hole Transporting Material Enables Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transporting materials (HTMs) is significant to the stability of perovskite solar cells (PSCs). Here, we developed a novel star-shape arylamine HTM, termed Py-DB, with a pyrene core and carbon-carbon double bonds as the bridge units. Compared to the reference HTM (termed Py-C), the extension of the planar conjugation backbone endows Py-DB with typical intermolecular π-π stacking interactions and excellent solubility, resulting in improved hole mobility and film morphology. In addition, the lower HOMO energy level of the Py-DB HTM provides efficient hole extraction with reduced energy loss at the perovskite/HTM interface. Consequently, an impressive power conversion efficiency (PCE) of 24.33 % was achieved for dopant-free Py-DB-based PSCs, which is the highest PCE for dopant-free small molecular HTMs in n-i-p configured PSCs. The dopant-free Py-DB-based device also exhibits improved long-term stability, retaining over 90 % of its initial efficiency after 1000 h exposure to 25 % humidity at 60 °C. These findings provide valuable insights and approaches for the further development of dopant-free HTMs for efficient and reliable PSCs.

A Biodegradable Janus Sponge for Negative Pressure Wound Therapy.

Negative pressure wound therapy (NPWT) is effective in repairing serious skin injury. The dressing used in the NPWT is important for wound healing. In this paper, we develop biodegradable amphiphilic polyurethanes (PUs) and fabricate the PUs into sponges as wound dressings (Bi@e) with Janus pore architectures for NPWT. The Bi@e is adaptive to all the stages of the wound healing process. The Janus Bi@e sponge consists of two layers: the dense hydrophobic upper layer with small pores provides protection and support during negative pressure drainage, and the loose hydrophilic lower layer with large pores absorbs large amounts of wound exudate and maintains a moist environment. Additionally, antibacterial agent silver sulfadiazine (SSD) is loaded into the sponge against Escherichia coli and Staphylococcus aureus with a concentration of 0.50 wt%. The Janus sponge exhibits a super absorbent capacity of 19.53 times its own water weight and remarkable resistance to compression. In a rat skin defect model, the Janus Bi@e sponge not only prevents the conglutination between regenerative skin and dressing but also accelerates wound healing compared to commercially available NPWT dressing. The Janus Bi@e sponge is a promising dressing for the NPWT.

Identification of Hedyotis diffusa Willd-specific mRNA-miRNA-lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification.

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

The Effect of Uncertainty Training on the Improvement of Diagnostic Ability in Chinese Medical Students.

Objective: To evaluate the effect of the uncertainty training on improvement of students' diagnostic ability. Methods: Data were collected on 70 fifth-year medical students enrolled in the Case Discussion courses on Obstetrics and Gynecology in the spring of 2020. Of these students, 36 were in the uncertainty training group and 34 in the control group. The effect of training was evaluated by cognitively diagnostic assessment which mapped exam questions to 4 attributes assessing clinical reasoning and basic science knowledge. Results: Uncertainty training was able to improve students' ability to use basic science concepts for inference and problem solving, and the ability to integrate complex clinical information to arrive at a diagnosis. But it could not improve students' ability on the basic recall of foundational concepts and the ability to use basic science concepts in clinical reasoning. Medical students could do well in integrating complex clinical information although they didn't recall basic science knowledge well. Conclusion: Uncertainty training could be used as an effective teaching method in Case Discussion course on Obstetrics and Gynecology. However, students still need to improve their basic knowledge besides the training.

Multifunctional Interface Modification Enables Efficient and Stable HTL-Free Carbon-Electroded CsPbI2Br Perovskite Solar Cells.

In recent years, hole transport layer-free all-inorganic CsPbI2Br carbon-electroded perovskite solar cells (C-PSCs) have garnered significant attention due to a trade-off between stability and photovoltaic performance. However, there are inevitably many defects generated at the surfaces or grain boundaries of CsPbI2Br perovskite films, which will serve as carrier non-radiative recombination centers, and CsPbI2Br perovskite films are sensitive to water molecules to degrade, together with energy level mismatch between CsPbI2Br perovskite and carbon electrodes. Herein, 1-benzyl-3-methylimidazolium hexafluorophosphate (1-B-3-MIMPF6), an imidazolium-based ionic liquid simultaneously containing benzene ring and fluorine atoms, was introduced for the modification of the perovskite/carbon interface. The results showed that it could effectively reduce defects, enhance carrier transfer, mitigate carrier non-radiative recombination, facilitate energy alignment, and block moisture intrusion. Therefore, the photovoltaic performance of the modified PSCs with ITO/SnO2/CsPbI2Br/1-B-3-MIMPF6/carbon architecture has been boosted with a champion power conversion efficiency (PCE) of 13.47 %, open circuit voltage of 1.20 V, short circuit current density of 14.69 mA/cm2, and fill factor of 76 %. Moreover, the unencapsulated modified devices exhibited an improved stability and the PCE maintained 78 % of their initial PCE after 24 h storage at room temperature in a 30 %-35 % humidity environment, whereas that of the pristine devices dropped to almost zero.

Identifying the in vivo-induced antigenic genes is a strategy to develop DNA vaccine against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).

Nocardia seriolae has been identified as the causative agent of fish nocardiosis, resulting in serious economic losses in aquaculture. With an aim to screen potential candidates for vaccine development against N. seriolae, the in vivo-induced genes of N. seriolae in hybrid snakehead (Channa maculate ♀ × Channa argus ♂) model were profiled via in vivo-induced antigen technology (IVIAT) in the present study, and 6 in vivo-induced genes were identified as follows: IS701 family transposase (is701), membrane protein insertase YidC (yidC), ergothioneine biosynthesis glutamate-cysteine ligase (egtA), molybdopterin respectively-dependent oxidoreductase (mol), phosphoketolase family protein (Ppl), hypothetical protein 6747 (hp6747). Additionally, the yidC was inserted into eukaryotic expression vector pcDNA3.1-myc-his-A to construct a DNA vaccine named as pcDNA-YidC to evaluate immunoprotection in hybrid snakehead after artificial challenge with N. serioale. Results showed that the transcription of yidC was detected in spleen, trunk kidney, muscle and liver in vaccinated fish, suggesting that this antigenic gene can be recombinantly expressed in fish. Meanwhile, indexes of humoral immunity were evaluated in the vaccinated fish through assessing specific-antibody IgM and serum enzyme activities, including lysozyme (LZM), superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Quantitative real-time PCR analysis indicated that pcDNA-YidC DNA vaccine could notably enhance the expression of immune-related genes (CD4、CD8α、MHCIIα、TNFα、IL-1ß and MHCIα) in 4 tissues (spleen, trunk kidney, muscle and liver) of the vaccinated fish. Finally, an immuno-protection with a relative survival rate of 65.71 % was displayed in vaccinated fish in comparison to the control groups. Taken together, these results indicate that pcDNA-YidC DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, indicating that IVIAT is a helpful strategy to screen the highly immunogenic antigens for vaccine development against fish nocardiosis.

Artesunate-loaded solid lipid nanoparticles resist esophageal squamous cell carcinoma by inducing Ferroptosis through inhibiting the AKT/mTOR signaling.

Esophageal squamous cell carcinoma (ESCC) is a severe malignancy with high incidence and mortality rate in China, while the application of standard chemotherapeutic drugs for ESCC meets the barriers of high toxicity and multiple drug resistance (MDR). In recent years, the anticancer effects of artesunate (ART), a Chinese medicine monomer have gained extensive attentions due to its characteristics of low toxicity, high potency, and reversal of MDR. In this study, we develop the artesunate-loaded solid lipid nanoparticles (SLNART) to overcome the poor water solubility and bioavailability of ART, further improving the efficiency of ART on ESCC treatment. Especially mentioned, SLNART is shown to present marked inhibitory effects on ESCC development based on the induction of ferroptosis by two pathways included upregulating TFR to increase Fe2+ ions and inhibiting the AKT/mTOR signaling to downregulate GPX4. Collectively, this study is the first to pave a promising approach for ESCC therapy based on a strategy of developing SLNART to induce ferroptosis by mediating Fe2+ ions and AKT/mTOR signaling.