A wearable iontophoresis enables dual-responsive transdermal delivery for atopic dermatitis treatment.

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 µg cm-2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way.

Establishment of Cephalic Index by Computed Tomography in Sampled Chinese Children.

OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.

Predictive value of Doppler echocardiography parameters for cardiovascular events in patients with systemic lupus erythematosus.

BACKGROUND AND OBJECTIVES: This study aimed to assess the utility of Doppler echocardiography in evaluating left ventricular diastolic function, and prognosis in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A total of 286 SLE patients were selected along with 100 age- and gender-matched healthy individuals who underwent physical examinations. Clinical baseline characteristics were collected. Various Doppler echocardiographic parameters were measured and analyzed, including left ventricular posterior wall thickness (LVPWT), interventricular septal diameter (IVSD), left ventricular mass (LVM), LVM index (LVMI), and others. RESULTS: Compared to the control group, SLE patients exhibited significantly higher levels of C-reactive protein and lower levels of complement (C) 3 and C4 (p < .001). Doppler echocardiographic parameters showed significant differences between SLE patients and healthy controls, including increased LVPWT, IVSD, LVM, LVMI, peak A, PWI + Tei, E/e', TDI-Tei, and decreased e' and E/A (p < .001). Subgroup analyses indicated more severe ventricular diastolic dysfunction in patients with higher SLE activity and those who experienced cardiovascular events. Correlation analysis revealed positive associations of PWI + Tei, TDI-Tei, and GLS with SLE activity and cardiovascular events (p < .01). Multivariate logistic regression analysis identified LVMI, PWI + Tei, TDI-Tei, and GLS as significant predictors of cardiovascular events (p < .05). CONCLUSION: Doppler echocardiography is a valuable tool for the early diagnosis of left ventricular diastolic dysfunction in SLE patients. Key echocardiographic parameters, including LVMI, PWI + Tei, TDI-Tei, and GLS, are effective in predicting cardiovascular events, underscoring the importance of comprehensive cardiac function assessments in these patients.

Acupuncture combined with gonadotropin-releasing hormone agonists improves endometrial receptivity and pregnancy outcome in patients with recurrent implantation failure of in vitro fertilization-embryo transfer.

OBJECTIVE: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. METHODS: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. RESULTS: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. CONCLUSION: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

A Wearable Self-Charging Electroceutical Device for Bacteria-Infected Wound Healing.

The prolonged wound-healing process caused by pathogen infection remains a major public health challenge. The developed electrical antibiotic administration typically requires metal electrodes wired to a continuous power supply, restricting their use beyond clinical environments. To obviate the necessity for antibiotics and an external power source, we have developed a wearable synergistic electroceutical device composed of an air self-charging Zn battery. This battery integrates sustained tissue regeneration and antibacterial modalities while maintaining more than half of the initial capacity after ten cycles of chemical charging. In vitro bacterial/cell coculture with the self-charging battery demonstrates inhibited bacterial activity and enhanced cell function by simulating the endogenous electric field and dynamically engineering the microenvironment with released chemicals. This electroceutical device provides accelerated healing of a bacteria-infected wound by stimulating angiogenesis and modulating inflammation, while effectively inhibiting bacterial growth at the wound site. Considering the simple structure and easy operation for long-term treatment, this self-charging electroceutical device offers great potential for personalized wound care.

Development of an immune-related diagnostic predictive model for oral lichen planus.

Oral lichen planus (OLP) was a chronic inflammatory disease of unknown etiology with a 1.4% chance of progressing to malignancy. However, it has been suggested in several studies that immune system disorders played a dominant role in the onset and progression of OLP. Therefore, this experiment aimed to develop a diagnostic prediction model for OLP based on immunopathogenesis to achieve early diagnosis and treatment and prevent cancer. In this study, 2 publicly available OLP datasets from the gene expression omnibus database were filtered. In the experimental group (GSE52130), the level of immune cell infiltration was assessed using MCPcounter and ssGSEA algorithms. Subsequently, differential expression analysis and gene set enrichment analysis were performed between the OLP and control groups. The resulting differentially expressed genes were intersected with immunologically relevant genes provided on the immunology database and analysis portal database (ImmPort) website to obtain differentially expressed immunologically relevant genes (DEIRGs). Furthermore, the gene ontology and kyoto encyclopedia of genes and genomes analyses were carried out. Finally, protein-protein interaction network and least absolute shrinkage and selection operator regression analyses constructed a model for OLP. Receiver operating characteristic curves for the experimental and validation datasets (GSE38616) were plotted separately to validate the model's credibility. In addition, real-time quantitative PCR experiment was performed to verify the expression level of the diagnostic genes. Immune cell infiltration analysis revealed a more significant degree of inflammatory infiltration in the OLP group compared to the control group. In addition, the gene set enrichment analysis results were mainly associated with keratinization, antibacterial and immune responses, etc. A total of 774 differentially expressed genes was obtained according to the screening criteria, of which 65 were differentially expressed immunologically relevant genes. Ultimately, an immune-related diagnostic prediction model for OLP, which was composed of 5 hub genes (BST2, RNASEL, PI3, DEFB4A, CX3CL1), was identified. The verification results showed that the model has good diagnostic ability. There was a significant correlation between the 5 hub diagnostic biomarkers and immune infiltrating cells. The development of this model gave a novel insight into the early diagnosis of OLP.

Auxochrome Dimethyl-Dihydroacridine Improves Fluorophores for Prolonged Live-Cell Super-Resolution Imaging.

Superior photostability, minimal phototoxicity, red-shifted absorption/emission wavelengths, high brightness, and an enlarged Stokes shift are essential characteristics of top-tier organic fluorophores, particularly for long-lasting super-resolution imaging in live cells (e.g., via stimulated emission depletion (STED) nanoscopy). However, few existing fluorophores possess all of these properties. In this study, we demonstrate a general approach for simultaneously enhancing these parameters through the introduction of 9,9-dimethyl-9,10-dihydroacridine (DMA) as an electron-donating auxochrome. DMA not only induces red shifts in emission wavelengths but also suppresses photooxidative reactions and prevents the formation of triplet states in DMA-based fluorophores, greatly improving photostability and remarkably minimizing phototoxicity. Moreover, the DMA group enhances the fluorophores' brightness and enlarges the Stokes shift. Importantly, the "universal" benefits of attaching the DMA auxochrome have been exemplified in various fluorophores including rhodamines, difluoride-boron complexes, and coumarin derivatives. The resulting fluorophores successfully enabled the STED imaging of organelles and HaloTag-labeled membrane proteins.

The SlGRAS9-SlZHD17 transcriptional cascade regulates chlorophyll and carbohydrate metabolism contributing to fruit quality traits in tomato.

Some essential components of fleshy fruits are dependent on photosynthetic activity and carbohydrate metabolism. Nevertheless, the regulatory mechanisms linking chlorophyll and carbohydrate metabolism remain partially understood. Here, we uncovered the role of SlGRAS9 and SlZHD17 transcription factors in controlling chlorophyll and carbohydrate accumulation in tomato fruit. Knockout or knockdown of SlGRAS9 or SlZHD17 resulted in marked increase in chlorophyll content, reprogrammed chloroplast biogenesis and enhanced accumulation of starch and soluble sugars. Combined genome-wide transcriptomic profiling and promoter-binding experiments unveiled a complex mechanism in which the SlGRAS9/SlZHD17 regulatory module modulates the expression of chloroplast and sugar metabolism either via a sequential transcriptional cascade or through binding of both TFs to the same gene promoters, or, alternatively, via parallel pathways where each of the TFs act on different target genes. For instance, the regulation of SlAGPaseS1 and SlSUS1 is mediated by SlZHD17 whereas that of SlVI and SlGLK1 occurs only through SlGRAS9 without the intervention of SlZHD17. Both SlGRAS9 and SlZHD17 can also directly bind the promoter of SlPOR-B to regulate its expression. Taken together, our findings uncover two important regulators acting synergistically to manipulate chlorophyll and carbohydrate accumulation and provide new potential breeding targets for improving fruit quality in fleshy fruits.

Knockout of OsSPL10 confers enhanced glufosinate resistance in rice.

This study shows that OsSPL10 is a novel genetic locus of glufosinate resistance in rice. OsSPL10 negatively regulates the expression of OsGS genes and thereby decreases GS activity. Knockout of OsSLP10 thus enhances glufosinate resistance, making it a candidate gene for improvement of crop glufosinate and stress resistance.

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence.

Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.

The Application of Graphene Field-Effect Transistor Biosensors in COVID-19 Detection Technology: A Review.

Coronavirus disease 2019 (COVID-19) is a disease caused by the infectious agent of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). The primary method of diagnosing SARS-CoV-2 is nucleic acid detection, but this method requires specialized equipment and is time consuming. Therefore, a sensitive, simple, rapid, and low-cost diagnostic test is needed. Graphene field-effect transistor (GFET) biosensors have become the most promising diagnostic technology for detecting SARS-CoV-2 due to their advantages of high sensitivity, fast-detection speed, label-free operation, and low detection limit. This review mainly focus on three types of GFET biosensors to detect SARS-CoV-2. GFET biosensors can quickly identify SARS-CoV-2 within ultra-low detection limits. Finally, we will outline the pros and cons of the diagnostic approaches as well as future directions.

Identification of SRS transcription factor family in Solanum lycopersicum, and functional characterization of their responses to hormones and abiotic stresses.

The SHI RELATED SEQUENCE (SRS) family plays a vital role in the development of multiple plant organs such as floral meristem determinacy, organ morphogenesis, and signal transduction. Nevertheless, there is little understanding of the biological significance of tomato SRS family at this point. Our research identified eight SlSRS family members and classified them into three subfamilies based on phylogenetics, conserved motifs, and characteristic domain analysis. The intraspecies and interspecies collinearity analysis revealed clues of SRS family evolution. Many cis-elements related to hormones, stresses, and plant development can be found in the promoter region of SlSRS genes. All of eight SlSRS proteins were located in the nucleus and possessed transcriptional activity, half of which were transcriptional activators, and the other half were transcriptional repressors. Except for SlSRS1, which showed high transcript accumulation in vegetative organs, most SlSRS genes expressed ubiquitously in all flower organs. In addition, all SlSRS genes could significantly respond to at least four different plant hormones. Further, expression of SlSRS genes were regulated by various abiotic stress conditions. In summary, we systematically analyzed and characterized the SlSRS family, reviewed the expression patterns and preliminarily investigated the protein function, and provided essential information for further functional research of the tomato SRS genes in the determination of reproductive floral organs and the development of plants, and possibly other plants.

Calcineurin inhibitors or cyclophosphamide in the treatment of membranous nephropathy superimposed with FSGS lesions: a retrospective study from China.

BACKGROUND: Cyclophosphamide (CTX) and calcineurin inhibitors (CNIs) based regimens are recommended as immunosuppressive therapies for patients with idiopathic membranous nephropathy (IMN). Focal and segmental glomerular sclerosis (FSGS) lesions, which are common in membranous nephropathy (MN), are poor predictors of outcome. This study compared the differences of prognosis between two regimens in patients with IMN combined with FSGS lesions. METHODS: This retrospective study enrolled 108 patients with biopsy-proven IMN, accompanied with FSGS lesions, nephrotic syndrome and an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 who were treated with CTX or CNIs. We used propensity score matching (PSM) for balancing the confounding variables. RESULTS: During follow-up, 10 patients (10/55 [18.2%]; nine males) in the CNIs group showed a 50% decline in eGFR; eight had a not otherwise specified variant. Patients initially treated with CNIs had a significantly higher risk of progression to the primary outcome and a lower probability of complete or total remission. The relapse rate was higher in patients who initially received CNIs- than in those who received CTX-based treatment. Before PSM, age and 24-h urine protein level differed significantly between the groups. The PSM model included data from 72 patients. Worse outcomes were also noted among patients who initially received CNIs than those who received CTX-based treatments after matching. CONCLUSIONS: Patients with MN combined with FSGS lesions have a higher risk of renal functional decline and a higher rate of relapse after CNIs than after CTX therapy.

First report on the molecular detection of Enterocytozoon bieneusi in livestock and wildlife around Qinghai Lake in the Qinghai-Tibetan Plateau area, China.

Enterocytozoon bieneusi is considered to be a microsporidial species of humans and animals in the worldwide. Limited data have been reported on the prevalence and genotypes of E. bieneusi in livestock and wild animals around Qinghai Lake in the Qinghai-Tibetan Plateau area, which shares water sources, grasslands, and harsh climate with high altitudes. In this study, fecal samples from 110 Tibetan sheep, 128 yaks, 227 wild birds, 96 blue sheep (Pseudois nayaur) and 268 Przewalski's gazelle (Procapra przewalskii) around Qinghai Lake were collected, and then tested for E. bieneusi by PCR and sequencing analysis based on the ribosomal internal transcribed spacer. Among them, ten (9.09%) samples from Tibetan sheep, five (3.91%) from yaks, five (2.20%) from wild birds, one (1.04%) from wild blue sheep and two (0.75%) from Przewalski's gazelle were positive for E. bieneusi. Among sheep, there were nine E. bieneusi genotypes, including two known genotypes (BEB6 and J), and seven novel genotypes (named CHS18-CHS24). From yaks, four genotypes were identified, including two known ones (BEB4 and J) and two novel genotypes (named CHN15 and CHN16). While in wild animals, eight genotypes were found, including five different genotypes from wild bids, with three known genotypes (EbpC, J and NCF2), two novel genotypes (named CHWB1 and CHS24), and two genotypes from Przewalski's gazelle, with one known genotype J and one novel genotype CHWPG1, and one novel genotype CHWBS1 from blue sheep. According to the phylogenetic analysis, five isolates belonged to group 1, and the others were clustered into group 2. This study provides unique data on the epidemiological reports and potential risk factors for E. bieneusi in both domesticated livestock and wild animals around Qinghai Lake in the Qinghai-Tibetan Plateau area; it is important to better understand the molecular epidemiology and zoonotic potential of E. bieneusi in the Qinghai-Tibetan Plateau area.

Conductive Viologen Hydrogel Based on Hyperbranched Polyamidoamine for Multiple Stimulus-Responsive Drug Delivery.

The emergence of precision medicine and personalized pharmacotherapy has led to the development of advanced drug delivery systems that can respond to multiple stimuli. Conductive hydrogels have excellent electrical signal responsiveness and drug storage capabilities; however, current conductive hydrogels suffer from poor mechanical properties, low ionic conductivity, and high voltage. Herein, a covalently crosslinked viologen hydrogel was prepared using electroactive hyperbranched polyamidoamine (EHP) as the crosslinking center in a polymeric network. Attributed to its unique molecular architecture, this hydrogel exhibits improved mechanical properties (high tensile strength and desirable stretchability up to 1280%). Approvable ionic conductivity, biocompatibility, antibacterial properties, and wearable strain-sensing performance were also disclosed, ascribed to the participation of versatile viologen groups in the hydrogel structure. This hydrogel exhibited high efficiency in drug release (81.6%) at a lower voltage of -1.2 V. Moreover, fascinating pH-stimulus drug release behavior was also demonstrated in both acidic and alkalescent environments owing to the dramatic conformational transition of EHP. This work provides a new design strategy for conductive hydrogels for multiple stimulus-responsive drug delivery systems.

A rare case of cardiogenic shock caused by takotsubo syndrome associated with SARS-CoV-2 infection: The value of echocardiography in the diagnosis and monitoring of the efficacy of extracorporeal membrane oxygenation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly invades the respiratory system, but may also cause various cardiovascular complications. We report a rare case of myocarditis associated with SARS-CoV-2 infection. A 61-year-old man was admitted to the hospital with a positive nucleic acid test for SARS-CoV-2. A sudden increase in troponin level (up to .144 ng/mL) was observed on the 8th day after admission. He developed symptoms of heart failure and progressed rapidly to cardiogenic shock. Echocardiography on the same day showed reduced left ventricular ejection fraction, reduced cardiac output, and segmental ventricular wall motion abnormalities. Takotsubo cardiomyopathy associated with SARS-CoV-2 infection was considered based on the typical echocardiography findings. We immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. The patient was successfully withdrawn from VA-ECMO after 8 days following recovery of ejection fraction to 65% and all indicators qualifying the withdrawal criteria. Echocardiography plays an important role in dynamic monitoring of cardiac changes in such cases and can help determine the timing of extracorporeal membrane oxygenation treatment and withdrawal.

The antioxidant protein glutaredoxin 1 is essential for oxidative stress response and pathogenicity of Toxoplasma gondii.

Glutaredoxins (Grxs) are ubiquitous antioxidant proteins involved in many molecular processes to protect cells against oxidative damage. Here, we study the roles of Grxs in the pathogenicity of Toxoplasma gondii. We show that Grxs are localized in the mitochondria (Grx1), cytoplasm (Grx2), and apicoplast (Grx3, Grx4), while Grx5 had an undetectable level of expression. We generated Δgrx1-5 mutants of T. gondii type I RH and type II Pru strains using CRISPR-Cas9 system. No significant differences in the infectivity were detected between four Δgrx (grx2-grx5) strains and their respective wild-type (WT) strains in vitro or in vivo. Additionally, no differences were detected in the production of reactive oxygen species, total antioxidant capacity, superoxide dismutase activity, and sensitivity to external oxidative stimuli. Interestingly, RHΔgrx1 or PruΔgrx1 exhibited significant differences in all the investigated aspects compared to the other grx2-grx5 mutant and WT strains. Transcriptome analysis suggests that deletion of grx1 altered the expression of genes involved in transport and metabolic pathways, signal transduction, translation, and obsolete oxidation-reduction process. The data support the conclusion that grx1 supports T. gondii resistance to oxidative killing and is essential for the parasite growth in cultured cells and pathogenicity in mice and that the active site CGFS motif was necessary for Grx1 activity.