A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Visible-Light-Driven Coupling of 1,3,4-Oxadiazoles and Hydroxamic Acid Derivatives.

A visible-light-induced radical-radical cross-coupling reaction between 1,3,4-oxadiazoles and hydroxamic acid derivatives has been realized under base- and metal-free conditions. The protocol was characterized by broad substrate scope, excellent functional group tolerance, and simple operation procedures. By using this protocol, a variety of biologically important 5-aryl-1,3,4-oxadiazole-2-methylamines were obtained in good yields with excellent chemoselectivity.

Enhancement of endothelial function and attenuation of portal vein injury using mesenchymal stem cells carrying miRNA-25-3p.

The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.

The therapeutic potential of phosphodiesterase 9 (PDE9) inhibitors: a patent review (2018-present).

INTRODUCTION: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates. AREA COVERED: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present. EXPERT OPINION: Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.

Downregulation of DIP2B as a prognostic marker inhibited cancer proliferation and migration and was associated with immune infiltration in lung adenocarcinoma via CCND1 and MMP2.

Background: DIP2B is related to cancer progression. This study investigated the roles and pathways of DIP2B in lung adenocarcinoma (LUAD). Methods: DIP2B expression and the relationship between survival time of cancer patients and DIP2B expression were analyzed. The relationship between DIP2B expression and survival time in LUAD patients was evaluated by a meta-analysis. Cox and survival analyses were used to evaluate the prognostic factors and construct a prognostic nomogram. The mechanisms and effects of DIP2B and the relationship between DIP2B expression and the immune microenvironment were investigated using bioinformatics, CCK-8, western blotting, and transwell experiments. Results: DIP2B was overexpressed in LUAD tissues. DIP2B overexpression was associated with shorter prognosis and was an unfavorable risk factor for prognosis in LUAD patients. DIP2B co-expressed genes were involved in cell division, DNA repair, cell cycle, and others. Inhibition of DIP2B expression could downregulate the proliferation, migration, and invasion of LUAD A549 and H1299 cells, which was related to the decrease in CCND1 and MMP2 protein expression. BRCA1 overexpression was associated with short prognosis, and the nomogram formed by DIP2B and BRCA1 was associated with a poor prognosis in LUAD patients. DIP2B expression correlated with immune cells (such as CD8 T cells, Tcm, and iDCs) and cell markers. Conclusion: DIP2B is a potential biomarker of poor prognosis and the immune microenvironment in LUAD. Inhibition of DIP2B expression downregulated cancer cell proliferation, migration, and invasion, which might be related to the decrease in CCND1 and MMP2 protein expression. DIP2B-related nomograms might be useful tools for predicting the prognosis of LUAD patients.

Correlation between bone mineral density and type 2 diabetes mellitus in elderly men and postmenopausal women.

The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1-4 (L1-L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients.Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028 .

An Active Halide Catholyte Boosts the Extra Capacity for all-Solid-State Batteries.

Replacing flammable organic liquid electrolytes with nonflammable solid electrolytes (SEs) in lithium batteries is crucial for enhancing safety across various applications, including portable electronics, electric vehicles, and scalable energy storage. Since typical cathode materials do not possess superionic conductivity, Li-ion conduction in the cathode predominantly relies on incorporating a significant number of SEs as additives to form a composite cathode, which substantially compromises the energy density of solid-state lithium batteries. Here, we demonstrate a halide SE, Li3VCl6, which not only exhibits a decent Li+ conductivity, but more importantly, delivers a highly reversible capacity of approximately 80 mAh g-1 with an average voltage of 3 V versus Li+/Li. The ionic conductivity of Li3VCl6 experiences marginal fluctuations upon electrochemical lithiation/delithiation, as its prototypical solid-solution reaction results solely in a reduction of lithium vacancy. When combined with the traditional LiFePO4 cathode, the active Li3VCl6 catholyte enables an impressive capacity of 217.1 mAh g-1 LFP and about 50% increase in energy density compared with inactive catholytes. Harnessing the integrated mass of the catholyte-which can serve as an active material-presents an opportunity to boost the extra capacity, rendering it feasible in applications. This article is protected by copyright. All rights reserved.

Agarose-Based Hydrogel Film with Embedded Oriented Photonic Nanochains for Sensing pH.

Responsive photonic crystal hydrogel sensors are renowned for their colorimetric sensing ability and can be utilized in many fields such as medical diagnosis, environmental detection, food safety, and industrial production. Previously, our group invented responsive photonic nanochains (RPNCs), which improve the response speed of photonic crystal hydrogel sensors by at least 2 to 3 orders of magnitude. However, RPNCs are dispersed in a liquid medium, which needs a magnetic field to orient them for the generation of structural colors. In addition, during repeated use, the process of cleaning and redispersing can cause entanglement, breakage, and a loss of RPNCs, resulting in poor stability. Moreover, when mixing with the samples in liquid, the RPNCs may lead to the contamination of the samples being tested. In this paper, we incorporate one-dimensional oriented RPNCs with agarose gel film to prepare heterogeneous hydrogel films. Thanks to the non-responsive and porous nature of the agarose gel, the protons diffuse freely in the gel, which facilitates the fast response of the RPNCs. Furthermore, the "frozen" RPNCs in agarose gel not only enable the display of structural colors without the need for a magnet but also improve the cycling stability and long-term durability of the sensor, and will not contaminate the samples. This work paves the way for the application of photonic crystal sensors.

N-Salicyloyl Tryptamine Derivatives as Potent Neuroinflammation Inhibitors by Constraining Microglia Activation via a STAT3 Pathway.

Neuroinflammation is an important factor that exacerbates neuronal death and abnormal synaptic function in neurodegenerative diseases (NDDs). Due to the complex pathogenesis and the presence of blood-brain barrier (BBB), no effective clinical drugs are currently available. Previous results showed that N-salicyloyl tryptamine derivatives had the potential to constrain the neuroinflammatory process. In this study, 30 new N-salicyloyl tryptamine derivatives were designed and synthesized to investigate a structure-activity relationship (SAR) for the indole ring of tryptamine in order to enhance their antineuroinflammatory effects. Among them, both in vitro and in vivo compound 18 exerted the best antineuroinflammatory effects by suppressing the activation of microglia, which is the culprit of neuroinflammation. The underlying mechanism of its antineuroinflammatory effect may be related to the inhibition of transcription, expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) that subsequently regulated downstream cyclooxygenase-2 (COX-2) expression and activity. With its excellent BBB permeability and pharmacokinetic properties, compound 18 exhibited significant neuroprotective effects in the hippocampal region of lipopolysaccharides (LPS)-induced mice than former N-salicyloyl tryptamine derivative L7. In conclusion, compound 18 has provided a new approach for the development of highly effective antineuroinflammatory therapeutic drugs targeting microglia activation.

Immunological characteristics of CD103+CD161+ T lymphocytes on chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous disease characterized by local inflammation of the upper airway and sinus mucosa. T cell-mediated immune responses play irreplaceable roles in the pathogenesis of nasal polyps. CD161+ T cells have been implicated in the pathology of several diseases through cytokine production and cytotoxic activity. However, the immunological characteristics of CD161+ T cells in nasal mucosa are still not well understood, particularly in CRSwNPs. Our research revealed a notable enrichment of CD161+ T cells in nasal tissues compared to peripheral blood, with a significantly more infiltration of CD161+ T cells in CRSwNPs compared to control nasal samples. Phenotypical analysis found that CD161+ T cells predominantly co-expressed tissue-resident memory surface markers CD103, CD69, and CD45RO. CD161+CD103+ T cells demonstrated complicated effector functions, marked by elevated levels of PD-1, CTLA-4, IL-17, and IFN-γ and diminished expression of FoxP3 and CD25. Interestingly, despite CD161+ T cells was more abundant in polyp tissues compared to normal control tissues, and then further categorizing polyp samples into distinct groups based on clinical characteristics, only the recurrent CRSwNP group showed a significant reduction in CD161+CD8+ T cells compared to the primary CRSwNP group. This finding suggested the necessity for further research to comprehensively understand the underlying mechanisms and the broader significance of CD161+ T cells in the advancement and relapse of CRSwNPs.

The effect of behavioral activation play therapy in adolescents with depression: A study protocol for a randomized controlled trial.

BACKGROUND: Depression is a common psychological problem in adolescents worldwide. Although the World Health Organization recommends that members of this population engage in physical activity to reduce depressive symptoms, compliance with this recommendation is often low. Furthermore, although behavioral activation (BA) is recommended as a treatment for adolescents with depression, the reported effect size is small. Compared with traditional exercises, gamified physical activity (GPA) can be particularly appealing to adolescents because it is perceived as an enjoyable experience. In this study, we integrated BA and GPA to create behavioral activation play therapy (BAPT). We designed a clinical trial to investigate the feasibility, acceptability, and effectiveness of this treatment in adolescents with depression. METHODS: This study is a randomized controlled trial (RCT) with a three-arm, assessor-blinded design, conducted to validate the effectiveness and applicability of BAPT for treating adolescent with depression. We will recruit 258 participants and randomly assign them to a BAPT group, BA group, or GPA group using a ratio of 1:1:1. Based on conventional strategies for treatment and care, the three groups will receive nine BAPT sessions, nine BA sessions, or nine GPA sessions, respectively. We will compare the outcomes of the BAPT with those of the BA and GPA interventions. DISCUSSION: This is the first RCT to explore the effectiveness and applicability of BAPT in adolescents with depression. This study will provide evidence that may help to decrease depressive symptoms in adolescents, and will demonstrate the treatment effectiveness in terms of increasing levels of physical activity, reducing the rate of non-suicidal self-injury behaviors, and improving sleep quality. We will also assess the presence of side effects and the treatment adherence of patients receiving BAPT. TRIAL REGISTRATION: Trial registration: Chinese Clinical Trial Registry, ChiCTR2300072671. Registered on 20 June 2023.

Associations between particulate matter exposure during pregnancy and executive function of toddlers in a prospective cohort study.

BACKGROUND: Exposure to particulate matter (PM) has been found to be associated with impaired cognitive function. However, limited evidence is available on the relationship between PM exposure in the prenatal period and toddler executive function (EF), and the potential influence of breastfeeding. METHODS: The study included 1106 mother-toddler pairs recruited between 2015 and 2019. We assessed mothers' PM1, PM2.5, and PM10 prenatal exposure with a satellite-based dataset at a 1 × 1 km spatial resolution and assigned to participants based on residential addresses. Toddler EF was measured using the Behavior Rating Inventory of Executive Function for Preschoolers (BRIEF-P) questionnaire, higher BRIEF-P scores indicated poorer EF in toddlers. We determined the associations of PM exposure during pregnancy with BRIEF-P scores using multiple linear regression models. RESULTS: In the first trimester, a 10 µg/m3 increase of PM was associated with 1.49 (95% confidence interval [CI]: 0.14-2.83; PM1), 0.68 (95% CI: 0.10-1.26; PM2.5), and 0.63 (95% CI: 0.07-1.20; PM10) elevated toddler global executive composite index scores, respectively. In the stratified analysis, a 10 µg/m3 increase in first trimester PM1 exposure was related to 0.54 (95% CI: 0.19-0.89) higher inhibition scores in toddlers who received complementary breastfeeding for less than six months and -0.15 (95% CI: 0.81-0.51) higher inhibition scores in toddlers who received complementary breastfeeding for six months or more (P for interaction: 0.046). Additionally, a 10 µg/m3 increment in first trimester PM1 exposure was related to 0.36 (95% CI: 0.13-0.59) higher emotional control scores in toddlers who received breastfeeding for less than 12 months and -0.54 (95% CI: 1.25-0.18) higher inhibition scores in toddlers who received breastfeeding for no less than 12 months (P for interaction: 0.043). CONCLUSIONS: PM exposure during the first trimester, especially PM1, has been linked to lower toddler EF performance in toddlers; feeding with breast milk may be a potential protective measure.

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

Objective: The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. Methods: We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. Results: For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1µmol/L, Cit higher than 26 µmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Conclusion: Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

Distribution and health risk of chromium in wheat grains at the national scale in China.

Chromium (Cr) pollution may threaten food safety in China. In this study, the concentration, pollution level, distribution, and non-cancer risk of Cr in wheat grains grown in 186 areas across 28 provinces in China were investigated. Results indicated that mean concentration of Cr was 0.28 ± 2.5 mg/kg, dry mass (dm). Of the samples, 7.5 % were found to be polluted with Cr. The mean concentrations were in the following order: Northwest > Northeast > South > East > North > Southwest > Central China. Based on deterministic models, mean hazard quotient (HQ) values for adult males, adult females, and children were 0.11 ± 3.4, 0.11 ± 3.4, and 0.13 ± 3.5, respectively with < 6 % of HQ values ≥ 1. Eleven sites in northern China were identified as hotspots, whereas Gansu Province and Northwestern China were labeled as priority provinces and regions for risk control. The mean HQ values estimated by probabilistic risk assessment were two times greater than those estimated using deterministic models. The risk probabilities for adult males, adult females, and children were 4.81 %, 3.78 %, and 6.55 %, respectively. This study provides valuable information on Cr pollution in wheat grains and its risks at a national scale in China.

Stabilizing atomic Ru species in conjugated sp2 carbon-linked covalent organic framework for acidic water oxidation.

Suppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g-1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.

Investigating the genetic determination of duration-of-fertility trait in breeding hens.

The duration-of-fertility (DF), which was defined as the number of days when breeding hens lay fertile eggs following copulation or artificial insemination (AI), is an important economic trait in chick production when it has strong effects on fertile egg output and production costs. Little is known about the underlying genes and molecular markers related to DF trait to date. Here, we measured the DF of 701 Chinese Jinghong hens and 408 Jingfen hens. The DF showed high individual variability and potential for genetic improvement. Then, 192 Jinghong breeding hens were provided for a genome-wide association study, 27 SNPs respectively located in three genomic linkage regions (GGA1:41Kb; GGA3:39Kb and GGA8:39Kb) were suggested to be significantly associated with DF. Particularly, 6 of these 27 SNPs were further verified to be associated with DF in the 701 Jinghong and 408 Jingfen hens using PCR-RFLP genotyping method. These 27 SNPs were also mapped to 7 genes according to their genomic position. Furtherly, 5 of these 7 genes were tested using qPCR. Results show that the CYP2D6, WBP2NL, ESR1 and TGFBR3 mRNA expression levels of hens with long DF were significantly higher than the hens with short DF (P < 0.05). Overall, findings in our research provide new insight into the genetic basis of duration-of-fertility in breeding hens while providing new clues for further functional validation on the DF-related genetic regulation mechanism and improvement of DF through chicken breeding.

Skin-inspired, sensory robots for electronic implants.

Drawing inspiration from cohesive integration of skeletal muscles and sensory skins in vertebrate animals, we present a design strategy of soft robots, primarily consisting of an electronic skin (e-skin) and an artificial muscle. These robots integrate multifunctional sensing and on-demand actuation into a biocompatible platform using an in-situ solution-based method. They feature biomimetic designs that enable adaptive motions and stress-free contact with tissues, supported by a battery-free wireless module for untethered operation. Demonstrations range from a robotic cuff for detecting blood pressure, to a robotic gripper for tracking bladder volume, an ingestible robot for pH sensing and on-site drug delivery, and a robotic patch for quantifying cardiac function and delivering electrotherapy, highlighting the application versatilities and potentials of the bio-inspired soft robots. Our designs establish a universal strategy with a broad range of sensing and responsive materials, to form integrated soft robots for medical technology and beyond.

Photonic Nanochains for Continuous Glucose Monitoring in Physiological Environment.

Diabetes is a common disease that seriously endangers human health. Continuous glucose monitoring (CGM) is important for the prevention and treatment of diabetes. Glucose-sensing photonic nanochains (PNCs) have the advantages of naked-eye colorimetric readouts, short response time and noninvasive detection of diabetes, showing immense potential in CGM systems. However, the developed PNCs cannot disperse in physiological environment at the pH of 7.4 because of their poor hydrophilicity. In this study, we report a new kind of PNCs that can continuously and reversibly detect the concentration of glucose (Cg) in physiological environment at the pH of 7.4. Polyacrylic acid (PAA) added to the preparation of PNCs forms hydrogen bonds with polyvinylpyrrolidone (PVP) in Fe3O4@PVP colloidal nanoparticles and the hydrophilic monomer N-2-hydroxyethyl acrylamide (HEAAm), which increases the content of PHEAAm in the polymer shell of prepared PNCs. Moreover, 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA), with a relatively low pKa value, is used as the glucose-sensing monomer to further improve the hydrophilicity and glucose-sensing performances of PNCs. The obtained Fe3O4@(PVP-PAA)@poly(AFPBA-co-HEAAm) PNCs disperse in artificial serum and change color from yellow-green to red when Cg increases from 3.9 mM to 11.4 mM, showing application potential for straightforward CGM.

FOXL2 regulates RhoA expression to change actin cytoskeleton rearrangement in granulosa cells of chicken pre-ovulatory follicles.

Forkhead box L2 (FOXL2) is an indispensable key regulator of female follicular development, and it plays important roles in the morphogenesis, proliferation, and differentiation of follicle granulosa cells (GCs), such as establishing normal estradiol signaling and regulating steroid hormone synthesis. Nevertheless, the effects of FOXL2 on GC morphology and the underlying mechanism remain unknown. Using FOXL2 ChIP-seq analysis, we found that FOXL2 target genes significantly enriched in the actin cytoskeleton-related pathways. We confirmed that FOXL2 inhibited the expression of RhoA, a key gene for actin cytoskeleton rearrangement, by binding to TCATCCATCTCT in RhoA promoter region. In addition, the overexpression of FOXL2 in GCs induced the depolymerization of F-actin and the disordered of the actin filaments, resulting in a slowdown in the expansion of GCs, while silencing FOXL2 inhibited F-actin depolymerization and stabilized the actin filaments, thereby accelerating GC expansion. RhoA/ROCK pathway inhibitor Y-27632 exhibited similar effects to FOXL2 overexpression, even reversed the actin polymerization in FOXL2 silencing GCs. This study revealed for the first time that FOXL2 regulated GC actin cytoskeleton by RhoA/ROCK pathway, thus affecting GC expansion. Our findings provide new insights for constructing the regulatory network of FOXL2 and propose a potential mechanism for facilitating rapid follicle expansion, thereby laying a foundation for further understanding follicular development.

Harnessing Disparities in Magnetic Microswarms: From Construction to Collaborative Tasks.

Individual differences in size, experience, and task specialization in natural swarms often result in heterogeneity and hierarchy, facilitating efficient and coordinated task accomplishment. Drawing inspiration from this phenomenon, a general strategy is proposed for organizing magnetic micro/nanorobots (MNRs) with apparent differences in size, shape, and properties into cohesive microswarms with tunable heterogeneity, controlled spatial hierarchy, and collaborative tasking capability. In this strategy, disparate magnetic MNRs can be manipulated to show reversible transitions between synchronization and desynchronization by elaborately regulating parameter sets of the rotating magnetic field. Utilizing these transitions, alongside local robust hydrodynamic interactions, diverse heterospecific pairings of disparate magnetic MNRs can be organized into heterogeneous microswarms, and their spatial organization can be dynamically adjusted from egalitarian to leader-follower-like hierarchies on the fly, both in open space and complex microchannels. Furthermore, when specializing the disparate MNRs with distinct functions ("division of labor") such as sensing and drug carrying, they can execute precise drug delivery targeting unknown sites in a collaborative sensing-navigating-cargo dropping sequence, demonstrating significant potential for precise tumor treatment. These findings highlight the critical roles of attribute differences and hierarchical organization in designing efficient swarming micro/nanorobots for biomedical applications.