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Summary: Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

Adenovirus (Ad) is a non-enveloped linear double-stranded DNA virus with >50 serotypes in humans. Ad vectors have been used as gene delivery vehicles to express transgenes, small interfering RNAs (siRNAs) for gene silencing, or CRISPR/Cas and designer nucleases for genome editing. Although several methods are used to generate Ad vectors, the Ad-making process remains technically challenging and time consuming. Moreover, the Ad-making techniques have not been improved for the past two decades. Gibson DNA Assembly (GDA) technology allows one-step isothermal DNA assembly of multiple overlapping fragments. Here, we developed a one-step construction of Ad (OSCA) system using GDA technology. Specifically, we first engineered several adenoviral recipient vectors that contain the ccdB suicide gene flanked with two 20-bp unique sequences, which serve as universal sites for GDA reactions in the Ad genome ΔE1 region. In two proof-of-principle experiments, we demonstrated that the GDA reactions were highly efficient and that the resulting Ad plasmids could be effectively packaged into Ads. Ad-mediated expression of mouse BMP9 in mesenchymal stem cells was shown to effectively induce osteogenic differentiation both in vitro and in vivo. Collectively, our results demonstrate that the OSCA system drastically streamlines the Ad-making process and should facilitate Ad-based applications in basic, translational, and clinical research.

Finger joint motion monitoring is crucial for rehabilitation training and ergonomics. Based on a multilayer dielectric structure, this study proposed flexible and highly sensitive ionic skins (sensors) for the measurement of the bending angles of finger joints. Each ionic skin, consisting silicon rubber films (multiple dielectric layers) and highly stretchable ionic conductors, was attached to the finger joint surface. The capacitance change of the skin was captured and used to measure finger joint bending angles. On this basis, the relationship between angles and capacitance variations was established. The relationship agreed with the experimental results. Furthermore, the effect of number of dielectric layers on sensitivity and linearity was discussed. The experimental results indicated that an increase in the number of dielectric layers improved sensitivity but suppressed linearity. The proposed ionic skins provided higher sensitivity and linearity than other flexible sensors. The five-layer ionic skin was four times more sensitive than existing ionic skins. The results confirmed that the multilayer dielectric structure of our ionic skins substantially enhanced the sensitivity for finger joint bending angle measurements.

RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.

Objective: Zishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women’s health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB). Results: Compared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P

Objective: Zishen Yutai Pill (ZYP), containing 15 Chinese traditional medicine, is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction. The current study was designed to investigate the therapeutic effects of ZYP on sperm quality and testis in varicocele (VC) rats. Materials and methods: Male Wistar rats were randomly divided into four groups (n = 6), i.e., a sham group, a VC group, and VC groups treated with different dose of ZYP (1575 and 3150 mg/kg/d, respectively). The experimental VC model was established by partial ligation of left renal vein. Six weeks after model establishment, ZYP was orally administered once a day for the next 6 weeks. Parameters relating to testis and sperm quality were assessed. Hematoxylin–eosin staining was used to showed testicular tissue damage in experimental VC rats. Expressions of proteins relating to NLRP3 inflammasome pathways were determined using Western blot (WB). The mRNA expressions of relating genes were determined using quantitative real-time PCR (qRT-PCR) analysis. Results: ZYP could significantly improve sperm motility and decrease sperm DNA fragmentation index in VC rats (P

Background: Zishen Guchong Pill (ZGP), a traditional oriental herbal medicine, has been applied broadly in the treatment of threatened or recurrent miscarriages in clinics, but little is known about its developmental toxicity.Aim of the study: This study aimed to investigate the potential toxicity of ZGP and its mechanisms.methods: We investigated the developmental toxicity of ZGP using a zebrafish model. Zebrafish embryos at 4 hours post-fertilization (hpf) were exposed to 25, 50, 100, and 200 µg/mL ZGP until 120 hpf. The zebrafish morphology, organ development, reactive oxygen species (ROS) content, oxidative stress-related enzyme activity, and mRNA levels of oxidative stress and apoptosis-related genes were measured.Results: Our results demonstrated that ZGP had no toxicity at 50 µg/mL ZGP but induced phenotypic defects and decreased the hatching rate and body length at more than 50 µg/mL ZGP (high dose). High doses of ZGP caused severe heart failure, including a significant increase in the sinus venosus (SV) and bulbus arteriosus (BA) distance and pericardial area, and reduced heart rate and numbers of red blood cells. In addition, high doses of ZGP caused liver atrophy and decreased the length of dopamine ganglia and neurovascular. High doses of ZGP elicited the generation of ROS and elevated malondialdehyde levels, but reduced the activity of superoxide dismutase (SOD) and catalase (CAT). Real-time PCR data showed the downregulation of oxidative stress-related genes (sod and cat) and the activation of Nrf2 (nrf2, keap1, ho-1, nqo1, gclc, and gclm) and P53 (p53, bcl-2, and bax) signal pathway genes after high ZGP exposure.Conclusions: Taken together, our results indicate that ZGP has no developmental toxicity under 50 µg/mL ZGP but induced developmental toxicity in zebrafish embryos at more than 50 µg/mL ZGP, and oxidative stress contributed to the toxic response. • ZGP is safe and reliable in clinical use. • ZGP (high does) caused an increase in ROS, which induced oxidative stress, leading to apoptosis and developmental toxicity. • The Nrf2 signaling pathway is impaired during the early stages of ZGP-induced developmental toxicity.

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57–84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p

Summary: Adhesive hydrogels containing catechol moieties have many important applications, but the fabrication of effective long-lasting adhesive hydrogels remains a challenge because of oxidative damage. Inspired by the traditional use of quercetin in ancient China, here, we have developed a novel method, based on quercetin-assisted photoradical chemistry, to fabricate a durable adhesive hydrogel, Q-hydrogel. In the presence of light, quercetin generates quinone/semiquinone radicals, which subsequently interact with ammonium persulfate (APS) to produce a large amount of free radicals and initiate polymerization of the hydrogel. As-prepared Q-hydrogel showed good mechanical and adhesive properties, which were attributed to the inherent structural advantages of quercetin. Because of the resistance of quercetin to oxidation, as-prepared Q-hydrogel also showed good adhesive properties even after treatment with oxidizing agents. Capitalizing on its conductivity and adhesive properties, Q-hydrogel was successfully used to produce wearable sensors capable of detecting human motion.

Male sterility induced by a chemical hybridization agent (CHA) is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in this study. CHA induced programmed cell death (PCD) as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and DNA laddering analysis. In the early phase, CHA-SQ-1 trig-gered organelle changes and PCD in wheat leaves accompanied by excess production of reactive oxygen species (O2 and H2O2) and down-regulation of the activities of superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (POD). Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-1-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.