Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Effectivenss of electroacupuncture for skeletal muscle pain in Parkinson's disease: a Clinical randomized controlled trial.

OBJECTIVE: To explore the effect of electroacupuncture on skeletal muscle pain in Parkinson's disease (PD). METHODS: A single-center randomized controlled trial was conducted with sixty patients with Parkinson's disease with skeletal muscle pain were randomly divided into electroacupuncture group and sham acupuncture control group with 30 patients each. The electric acupuncture group was treated with electric acupuncture, while the control group was treated with Park needle pseudoacupuncture. Both groups were treated 5 times a week for a total of 4 weeks, and both groups completed 20 treatments. King's Parkinson's Pain Scale (KPPS) and visual analog scale (VAS) were used before and after treatment to evaluate the pain degree of patients. Real-time shear wave elastography (SWE) and modified Ashworth score (MAS) were used to evaluate the changes of muscle tone. Parkinson's comprehensive Score Scale (MDS-UPDRS, including UPDRSⅡ and UPDRS Ⅲ) was used to evaluate exercise ability. Hamilton Depression Scale (HAMD) score was used to evaluate the emotional changes of patients. Spearman correlation analysis was used to explore the correlation between pain degree and muscle tone, exercise ability and emotion. RESULTS: During the study, one case fell off in the control group, and 30 cases were eventually included in the analysis and treatment group and 29 cases in the control group. After treatment, Young's modulus of biceps and quadriceps and shear wave velocity of biceps were decreased in electroacupuncture group compared with before treatment, while KPPS score, VAS score, UPDRSⅡ, UPDRS Ⅲ and modified Ashworth score were decreased, with statistical significance (P < 0.05). There was no statistical significance in control group (P > 0.05). After treatment, KPPS score, VAS score, UPDRSⅡ and UPDRS Ⅲ, MAS, HAMD score, Young's modulus of biceps and shear wave velocity in electroacupuncture group were significantly lower than those in control group (P < 0.05). Spearman correlation analysis showed that KPPS score was positively correlated with UPDRS Ⅲ (r = 0.414, P < 0.05). KPPS score was positively correlated with HAMD score (r = 0.576, P < 0.01). CONCLUSION: Electroacupuncture therapy can effectively improve skeletal muscle pain in patients with Parkinson's disease, reduce the muscle hardness of patients, improve patients' daily life ability, and improve patients' emotional disorders. The degree of skeletal muscle pain in PD patients is correlated with motor ability and emotional disorders, but there is no significant correlation between the degree of skeletal muscle pain and the muscle tone of PD patients.

[Ecological network optimization of Jiuquan City, Gansu, China based on complex network theory and circuit model]. / åŸºäºŽå¤æ‚ç½‘ç»œç†è®ºå’Œç”µè·¯æ¨¡åž‹çš„é ’æ³‰å¸‚ç”Ÿæ€ç½‘ç»œä¼˜åŒ–.

Building a scientific and reasonable ecological network is the key for optimizing the pattern of territorial development and protection, and is of great significance for ensuring regional ecological security and promoting the virtuous cycle of ecosystems. In previous studies, nodal attack method (destruction of ecological source area) was often used in the "robustness" evaluation of ecological networks. Actually, the ecological corridor is more fragile than the source area, and thus the nodal attack method is not reasonable. In this study, taking Jiuquan City as the research area, based on the circuit model to construct the ecological network, we carried out the topology optimization of ecological network by using three strategies (random edge increase, node degree and priority edge increase with low node intermedium number) in complex network theory. We compared and analyzed the "robustness" of ecological network before and after optimization by constructing edge attack strategy, and selected the best network optimization strategy. The results showed that 65 ecological source areas were identified in Jiuquan City, with a total area of 20275.15 km2, and that grassland accounted for 89.5% of the source area. We identified 179 ecological corridors with a total length of 6387.16 km, 158 ecological barrier points with a total area of 1385.5 km2. The unused land accounted for 92.2% of the total barrier points area. We identified 63 ecological pinch points, mainly concentrated in the source edge and corridor intersection. Among them, the spatial distribution of 11 barrier points and pinch points was consistent, which was the key area to be repaired in ecological network optimization. The three optimization strategies had significantly improved the stability of ecological network in Jiuquan City. The relative size of the maximum connected subgraph and the edge connected rate of the ecological network of the optimization strategy of adding edges according to degree were all the most stable under random attack mode and deliberate attack mode, which was the best optimization scheme for ecological network in Jiuquan City.

tRNAGlu-derived fragments from embryonic extracellular vesicles modulate bovine embryo hatching.

Transfer RNA-derived small RNAs (tsRNAs) have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem cells. However, it is unknown whether tsRNAs also regulate embryo hatching. In this study, we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA (miRNA) cargo of preimplantation embryonic extracellular vesicles (EVs) influences embryo development. We thus profiled the tsRNA cargo of EVs secreted by blastocysts and non-blastocysts. The majority of tsRNAs was identified as tRNA halves originating from the 5´ ends of tRNAs. Among the 148 differentially expressed tsRNAs, the 19 nt tRNA fragment (tRF) tDR-14:32-Glu-CTC-1 was found to be significantly up-regulated in EVs derived from non-blastocysts. RT-qPCR assays confirmed its significant up-regulation in non-blastocyst embryos and their conditioned medium compared to the blastocyst group (P < 0.05). Inhibition of tDR-14:32-Glu-CTC-1 by supplementing antagomirs to the conditioned medium improved embryo hatching (P < 0.05). Transcriptomic analysis of embryos treated with tDR-14:32-Glu-CTC-1 antagomirs further showed differential expression of genes that are associated with embryo hatching and implantation. In summary, tDR-14:32-Glu-CTC-1 is up-regulated in non-blastocyst embryos and their secretions, and inhibition of tDR-14:32-Glu-CTC-1 promotes embryo hatching, while influencing embryo implantation-related genes and pathways. These results indicate that embryonic EVs containing specific tRFs may regulate preimplantation embryo development.

Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort.

BACKGROUND: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. METHODS: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. RESULTS: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). CONCLUSION: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.

Molecular Engineering Enables Hydrogel Electrolyte with Ionic Hopping Migration and Self-Healability toward Dendrite-Free Zinc-Metal Anodes.

Hydrogel electrolytes (HEs), characterized by intrinsic safety, mechanical stability, and biocompatibility, can promote the development of flexible aqueous zinc-ion batteries (FAZIBs). However, current FAZIB technology is severely restricted by the uncontrollable dendrite growth arising from undesirable reactions between the HEs with sluggish ionic conductivity and Zn metal. To overcome this challenge, this work proposes a molecular engineering strategy, which involves the introduction of oxygen-rich poly(urea-urethane) (OR-PUU) into polyacrylamide (PAM)-based HEs. The OR-PUU/PAM HEs facilitate rapid ion transfer through their ionic hopping migration mechanism, resulting in uniform and orderly Zn2+ deposition. The abundant polar groups on the OR-PUU molecules in OR-PUU/PAM HEs break the inherent H-bond network, tune the solvation structure of hydrated Zn2+, and inhibit the occurrence of side reactions. Moreover, the interaction of hierarchical H-bonds in the OR-PUU/PAM HEs endows them with self-healability, enabling in situ repair of cracks induced by plating/stripping. Consequently, Zn symmetric cells incorporating the novel OR-PUU/PAM HEs exhibit a long cycling life of 2000 h. The resulting Zn-MnO2 battery displays a low capacity decay rate of 0.009% over 2000 cycles at 2000 mA g-1. Overall, this work provides valuable insights to facilitate the realization of dendrite-free Zn-metal anodes through the molecular engineering of HEs.

Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients.

BACKGROUND: Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. METHODS: Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. RESULTS: The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013-0.915). CONCLUSION: Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

[Spatial-Temporal Evolution and Prediction of Carbon Storage in Jiuquan City Ecosystem Based on PLUS-InVEST Model].

Based on the background of carbon peaking and carbon neutrality goal strategies, it is important to explore the impact of land use change on carbon storage and the drivers of spatial variation in carbon storage in the Northwest Arid Zone, which is vital to improve the carbon sink increment of the regional ecosystem and promote the regional carbon breakeven. The arid region of northwest China is an extremely fragile natural ecology, and with the rapid advancement of new urbanization, the rate of land use change has accelerated significantly, which has a certain impact on the carbon storage and fixation capacity of ecosystems. The PLUS-InVEST model was used to simulate the spatial and temporal evolution characteristics of carbon storage under natural development, intensive development, water resource constraint, and ecological protection scenarios in Jiuquan City in 2035, and the parameter optimal geographic detector model was used to analyze the spatial divergence drivers of carbon storage. The results showed that:① the area of cultivated land, watershed, and construction land in Jiuquan City showed a significant increasing trend from 1990 to 2020, whereas the area of the remaining land use types showed a decreasing trend. ② The carbon storage in Jiuquan City increased from 7 722 808.1 t to 7 784 371 t from 1990 to 2020, and the conversion of grassland into unused land was the main cause of the loss of regional carbon storage, accounting for 85% of the total loss. ③ All four development scenarios in 2035 showed an increasing trend of carbon storage, among which the ecological protection scenario had the most significant increase, with an increment of 76 989.29 t. ④ The degree of land use, population density, GDP density, and NDVI were the main driving factors of the spatial variation in carbon storage in Jiuquan City, among which the degree of land use had the strongest explanatory power (q value of 0.849), and the interaction of natural and anthropogenic factors enhanced the explanatory power of each factor on the spatial variation in carbon storage. The results of the study can provide a scientific basis and decision basis for the integrated ecosystem management and territorial space optimization in Jiuquan City.

Impacts of climate change and human activity on the potential distribution of Aconitum leucostomum in China.

Aconitum leucostomum is a poisonous grass that disturbs grassland populations and livestock development, and its spread is influenced by climate change and human activities. Therefore, exploring its potential distribution area under such conditions is crucial to maintain grassland ecological security and livestock development. The present study initially selected 39 variables that may influence the spatial distribution of A. leucostomum, including bioclimate, soil, topography, solar radiation, and human footprint data; the variables were screened by Spearman's correlation coefficient and the jackknife method. Twenty variables were finally identified, and three types of models based on the maximum entropy (MaxEnt) model were constructed to predict the distribution of A. leucostomum within China under three shared economy pathways (SSP126, SSP245, and SSP585): A: prediction of environmental variables under the current climate model; B: prediction of environmental variables + human footprint under the current climate model; and C: prediction of environmental variables under the future climate model (including the 2030s, 2050s, and 2070s). The effects of human activities and climate change on the potential geographic distribution of A. leucostomum were explored separately. The results show that precipitation seasonality, human footprint, solar radiation and mean diurnal range are the main factors affecting the distribution of A. leucostomum. Human activities inhibit the spread of A. leucostomum, and climate change promotes its growth, with areas of high suitability and area variation mainly in northern Xinjiang and northern Yunnan. With climate change, in the future, the distribution center of A. leucostomum shows a tendency to migrate to the southeast on the horizontal gradient and to move to higher altitudes on the vertical gradient. This study provides a positive reference value for the control of A. leucostomum and the maintenance of grassland ecological security.

Spotlight on iron overload and ferroptosis: Research progress in female infertility.

Iron is an essential trace element for organisms. However, iron overload, which is common in haematological disorders (e.g. haemochromatosis, myelodysplastic syndromes, aplastic anaemia, and thalassaemia, blood transfusion-dependent or not), can promote reactive oxygen species generation and induce ferroptosis, a novel form of programmed cell death characterised by excess iron and lipid peroxidation, thus causing cell and tissue damage. Infertility is a global health concern. Recent evidence has indicated the emerging role of iron overload and ferroptosis in female infertility by inducing hypogonadism, causing ovary dysfunction, impairing preimplantation embryos, attenuating endometrial receptivity, and crosstalk between subfertility-related disorders, such as polycystic ovary syndrome and endometriosis. In addition, gut microbiota and their metabolites are involved in iron metabolism, ferroptosis, and female infertility. In this review, we systematically elaborate on the current research progress in female infertility with a novel focus on iron overload and ferroptosis and summarise promising therapies targeting iron overload and ferroptosis to recover fertility in women. In summary, our study provides new insights into female infertility and offers literature references for the clinical management of female infertility associated with iron overload and ferroptosis, which may be beneficial for females with haematopoietic disorders suffering from both iron overload and infertility.

Improved method for modulation transfer function measurement of Bayer color cameras.

Aiming at the difficulty of detecting the modulation transfer function (MTF) of Bayer color cameras during focusing, the traditional scheme is modified in this paper. First, through analysis, it is found that the MTF of the Bayer detector decreased substantially compared to the monochromatic detector, which was caused by the loss of a large amount of light from the Bayer detector. When the MTF is calculated for the color image after de-mosaicing, the degradation of image quality leads to the inability to obtain the full-frequency MTF curve. Therefore, this paper proposes a solution to detect the MTFs of the three primary colors in the Bayer image individually, and then weight the MTFs of each primary color to obtain the MTF of the color image based on the calibration results of the light source. Then, considering the steps of differentiation and Fourier transform in the slanted-edge method, this paper solves the problem of non-uniform sampling of edge spread function by using the modification of the slanted-edge method with non-uniform Fourier transform. Finally, the optimal imaging position of a certain type of Bayer color camera is determined using the methods proposed in this paper. Simulation and test results verify the effectiveness and accuracy of the methods in this paper.

The clinical efficacy of laminectomy fusion fixation and posterior single open-door laminoplasty in the treatment of multilevel cervical ossification of the posterior longitudinal ligament (OPLL): a retrospective study.

BACKGROUND: To compared the clinical efficacy of two surgical methods, posterior laminectomy fusion fixation, and posterior single open-door laminoplasty, in treating multilevel cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: The study retrospectively included 102 patients treated between December 2016 and December 2020. The patients were included into an observation group (56 cases) treated with total laminectomy and lateral screw fixation, and a control group (46 cases) treated with single open-door laminoplasty. RESULTS: After 24 months, both groups showed significant improvement in Japanese Orthopaedic Association (JOA) scores and Visual Analogue Scale (VAS) scores, indicating better clinical symptoms and functional recovery. There was no significant difference in preoperative JOA and VAS scores between the two groups (P > 0.05). At 24 months after surgery, there was no significant difference in JOA and VAS scores between the two groups (P > 0.05). However, the observation group had a significantly higher cervical curvature index (CCI) and lower range of motion (ROM) of the cervical spine compared to the control group (P < 0.05). The CCI in control group was lower than before surgery, while the CCI in observation group was higher than before surgery, and CCI in the control group was considerably lower than that in the observation group (P < 0.05). The complication rate was lower in the control group, with fewer cases of axial symptoms, fifth cervical nerve root palsy, and overall complications. The overall complication rate was 25.0% (14/56) in the observation group and 10.8% (5/46) in the control group (P < 0.05). CONCLUSIONS: Both posterior laminectomy fusion fixation and posterior single open-door laminoplasty yield positive outcomes in improving clinical neurological function, cervical curvature, range of motion of the cervical spine, and cervical sagittal balance. Although open-door laminoplasty is less effective than total laminectomy in maintaining CCI and sagittal balance, it excels in preserving cervical range of motion, less surgical trauma and complications. Thus, open-door laminoplasty may be a suitable first-choice treatment for multi-segmental cervical OPLL, especially for patients with lordotic cervical spine physiological curvature.

Oral administration of hyaluronic acid to improve skin conditions via a randomized double-blind clinical test.

OBJECTIVE: To evaluate the impact of oral intake of Hyaluronic Acid (HA) on skin health. BACKGROUND: HA, an endogenous substance in the human body, plays a key role in skin health. However, its concentration in the skin decreases significantly with age. Previous studies suggested that oral intake of HA can supplement the body's HA level, but did not reveal the effects on different age groups and skin types. METHODS: A double-blind, randomized clinical trial with 129 female participants, covering young and elderly groups and differnet skin types, was conducted to assess the efficacy of orally administered HA on skin health. RESULTS: Oral administration of HA significantly promoted skin hydration after 2-8 weeks among both young and elderly groups. Skin tone improvement was observed after 4-8 weeks, while an increase in epidermal thickness was noted after 12 weeks. CONCLUSION: This study provides direct evidence supporting the clinical efficacy of oral intake of HA in promoting skin health.

Network Pharmacology Studies on the Molecular Mechanism of Hashimoto's Thyroiditis Treated with Shutiao Qiji Decoction.

BACKGROUND: In recent years, the number of patients with Hashimoto's thyroiditis has been increasing, and traditional Chinese medicine ingredients and combinations have been applied to treat Hashimoto's thyroiditis to increase efficacy and reduce side effects during the treatment process. OBJECTIVE: Shutiao Qiji Decoction is one of the Chinese traditional medicine prescriptions, which is commonly used to treat cancer, tumor, etc. It is also used for thyroid-related diseases in the clinic. Hashimoto's thyroiditis is an autoimmune disease. In this study, the mechanism of Shutiao Qiji Decoction in treating Hashimoto's thyroiditis was studied through network pharmacology and molecular docking verification. METHOD: Each Chinese medicine ingredient of Shutiao Qiji Decoction was retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The related genes of HT were searched from the UniProt and GeneCards databases. Meanwhile, we used Cytoscape to construct the protein-protein interaction (PPI) visual network analysis, and used the search tool to search the database of Interacting Genes (STRING) to build a PPI network. These key proteins were enriched and analyzed by molecular docking validation, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hashimoto's thyroiditis disease model was established in SD rats, and SQD was administered by gavage after the successful establishment of the model. After 6 weeks of continuous administration of the drug by gavage, tissue samples were collected and the thyroid and spleen tissues were visualized by HE staining to verify the therapeutic effect. RESULTS: The results showed that there were 287 TCM active ingredients, 1920 HT-related disease targets, and 176 drug and disease targets in SQD. Through PPI analysis, GP analysis, and KEGG analysis of the common targets of drugs and diseases, we found their pathways of action to be mainly cancer action pathway, PI3K-AKT signaling pathway, and T-cell action pathway. The active ingredients of the drugs in SQD, malvidin, stigmasterol, porin-5-en-3bta-ol, and chrysanthemum stigmasterol, were docked with the related target proteins, MAPK, GSK3ß, TSHR, and NOTCH molecules. The best binding energies obtained from docking were mairin with TSHR, stigmasterol with TSHR, poriferast-5-en-3beta-ol with MAPK, and chryseriol with GSK3ß, with binding energies of -6.84 kcal/mol, -6.53 kcal/mol, -5.03 kcal/mol, and -5.05 kcal/mol, respectively. HE staining sections of rat thyroid and spleen tissues showed that SQD had a therapeutic effect on Hashimoto's thyroiditis and restored its immune function. CONCLUSION: It is verified by molecular docking results that Shutiao Qiji Decoction has a potential therapeutic effect on Hashimoto's thyroiditis in the MAPK/TSHR/NOTCH signal pathway, and that the main components, mairin, stigmasterol, poriferast-5-en-3beta-ol, and chryseriol play a role in it. SQD has been shown to have a good therapeutic effect on Hashimoto's thyroiditis.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Recurrent Implantation Failure: Bioinformatic Discovery of Biomarkers and Identification of Metabolic Subtypes.

Recurrent implantation failure (RIF) is a challenging scenario from different standpoints. This study aimed to investigate its correlation with the endometrial metabolic characteristics. Transcriptomics data of 70 RIF and 99 normal endometrium tissues were retrieved from the Gene Expression Omnibus database. Common differentially expressed metabolism-related genes were extracted and various enrichment analyses were applied. Then, RIF was classified using a consensus clustering approach. Three machine learning methods were employed for screening key genes, and they were validated through the RT-qPCR experiment in the endometrium of 10 RIF and 10 healthy individuals. Receiver operator characteristic (ROC) curves were generated and validated by 20 RIF and 20 healthy individuals from Peking University People's Hospital. We uncovered 109 RIF-related metabolic genes and proposed a novel two-subtype RIF classification according to their metabolic features. Eight characteristic genes (SRD5A1, POLR3E, PPA2, PAPSS1, PRUNE, CA12, PDE6D, and RBKS) were identified, and the area under curve (AUC) was 0.902 and the external validated AUC was 0.867. Higher immune cell infiltration levels were found in RIF patients and a metabolism-related regulatory network was constructed. Our work has explored the metabolic and immune characteristics of RIF, which paves a new road to future investigation of the related pathogenic mechanisms.

Experimental Demonstration of Fully Passive Quantum Key Distribution.

The passive approach to quantum key distribution (QKD) consists of removing all active modulation from the users' devices, a highly desirable countermeasure to get rid of modulator side channels. Nevertheless, active modulation has not been completely removed in QKD systems so far, due to both theoretical and practical limitations. In this Letter, we present a fully passive time-bin encoding QKD system and report on the successful implementation of a modulator-free QKD link. According to the latest theoretical analysis, our prototype is capable of delivering competitive secret key rates in the finite key regime.

A General Deep Learning Method for Computing Molecular Parameters of a Viscoelastic Constitutive Model by Solving an Inverse Problem.

Prediction of molecular parameters and material functions from the macroscopic viscoelastic properties of complex fluids are of great significance for molecular and formulation design in fundamental research as well as various industrial applications. A general learning method for computing molecular parameters of a viscoelastic constitutive model by solving an inverse problem is proposed. The accuracy, convergence and robustness of a deep neural network (DNN)-based numerical solver have been validated by considering the Rolie-Poly model for modeling the linear and non-linear steady rheometric properties of entangled polymer solutions in a wide range of concentrations. The results show that as long as the DNN could be trained with a sufficiently high accuracy, the DNN-based numerical solver would rapidly converge to its solution in solving an inverse problem. The solution is robust against small white noise disturbances to the input stress data. However, if the input stress significantly deviates from the original stress, the DNN-based solver could readily converge to a different solution. Hence, the resolution of the numerical solver for inversely computing molecular parameters is demonstrated. Moreover, the molecular parameters computed by the DNN-based numerical solver not only reproduce accurately the steady viscoelastic stress of completely monodisperse linear lambda DNA solutions over a wide range of shear rates and various concentrations, but also predict a power law concentration scaling with a nearly same scaling exponent as those estimated from experimental results.

Free-standing conductive nickel metal-organic framework nanowires as bifunctional electrodes for wearable pressure sensors and Ni-Zn batteries.

Free-standing metal-organic frameworks (MOFs) with controllable structure and good stability are emerging as promising materials for applications in flexible pressure sensors and energy-storage devices. However, the inherent low electrical conductivity of MOF-based materials requires complex preparation processes that involve high-temperature carbonization. This work presents a simple method to grow conductive nickel MOF nanowire arrays on carbon cloth (Ni-CAT@CC) and use Ni-CAT@CC as the functional electrodes for flexible piezoresistive sensor. The resulting sensor is able to monitor human activity, including elbow bending, knee bending, and wrist bending. Besides, the soft-packaged aqueous Ni-Zn battery is assembled with Ni-CAT@CC, a piece of glass microfiber filters, and Zn foil acting as cathode, separator, and anode, respectively. The Ni-Zn battery can be used as a power source for finger pressure monitoring. This work demonstrates free-standing MOF-based nanowires as bifunctional fabric electrodes for wearable electronics.