Elucidating Iron Metabolism through Molecular Imaging.

Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology's potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.

Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection.

There has been an increase in the use of molecular probe diagnostic techniques for lung cancer, and magnetic resonance imaging (MRI) offers specific advantages for diagnosing pulmonary carcinoma. Furthermore, advancements in near-infrared II (NIR-II) fluorescence have provided a new method for precise intraoperative tumor resection. However, few probes combine preoperative diagnosis with intraoperative imaging. This study aims to fill this research void by employing a dual-modal probe that targets the epidermal growth factor receptor for MR and NIR-II imaging, enabling the preoperative diagnosis of lung cancer using MRI and precise intraoperative tumor localization using NIR-II with a single probe. The imaging effects and targeting ability of the probe were confirmed in cell lines, mouse models, and clinical samples. The MR signal decreased within 24 h in the patient-derived xenograft mouse model. The average signal-to-background ratio of NIR-II reached 3.98 ± 0.27. The clinical sample also showed a decrease in the T2 signal using MRI, and the NIR-II optical signal-to-background ratio was 3.29. It is expected that this probe can improve the diagnostic rate of lung cancer using MRI and enable precise intraoperative tumor resection using NIR-II.

Elucidating the potential of chlorogenic acid for controlling Morganella psychrotolerans growth and histamine formation.

AIM: To investigate the inhibitory impact of chlorogenic acid (CGA) on the growth of Morganella psychrotolerans and its ability to form histamine. METHODS AND RESULTS: The antimicrobial effect of CGA on M. psychrotolerans was evaluated using the minimum inhibitory concentration (MIC) method, revealing an MIC value of 10 mg ml-1. The alkaline phosphatase (AKP) activity, cell membrane potential, and scanning electron microscopy images revealed that CGA treatment disrupted cell structure and cell membrane. Moreover, CGA treatment led to a dose-dependent decrease in crude histidine decarboxylase (HDC) activity and gene expression of histidine decarboxylase (hdc). Molecular docking analysis demonstrated that CGA interacted with HDC through hydrogen bonds. Furthermore, in situ investigation confirmed the efficacy of CGA in controlling the growth of M. psychrotolerans and significantly reducing histamine formation in raw tuna. CONCLUSION: CGA had good activity in controlling the growth of M. psychrotolerans and histamine formation.

Bovine Pluripotent Stem Cells: Current Status and Prospects.

Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autologous cell lines. Since cattle are the most commonly used large domesticated animals, an important food source, and bioreactors, great efforts have been made to establish bovine PSCs (bPSCs). bPSCs have great potential in bovine breeding and reproduction, modeling in vitro differentiation, imitating cancer development, and modeling diseases. Currently, bPSCs mainly include bovine embryonic stem cells (bESCs), bovine induced pluripotent stem cells (biPSCs), and bovine expanded potential stem cells (bEPSCs). Establishing stable bPSCs in vitro is a critical scientific challenge, and researchers have made numerous efforts to this end. In this review, the category of PSC pluripotency; the establishment of bESCs, biPSCs, and bEPSCs and its challenges; and the application outlook of bPSCs are discussed, aiming to provide references for future research.

Enhancing Photocatalytic Activities for Sustainable Hydrogen Evolution on Structurally Matched CuInS2/ZnIn2S4 Heterojunctions.

Effective charge separation and migration pose a critical challenge in the field of solar-driven hydrogen production. In this work, a Z-scheme structured CuInS2/ZnIn2S4 heterojunction was successfully fabricated through a two-step hydrothermal synthesis method to significantly enhance the efficiency of solar-to-hydrogen energy conversion. Structural characterization revealed that the lattice-matched CuInS2/ZnIn2S4 heterojunction exhibits an enlarged interfacial contact area, which facilitates the transfer and separation of photogenerated charges. Microscopic analysis indicated that the CuInS2/ZnIn2S4 composite material has a tightly interwoven interface and a morphology resembling small sugar cubes. Photoelectrochemical spectroscopy analysis demonstrated that the heterojunction structure effectively enhances visible light absorption and charge separation efficiency, leading to an improvement in photocatalytic activity. Hydrogen production experimental data indicated that the CuInS2/ZnIn2S4 heterojunction photocatalyst prepared with a CuInS2 content of 20 wt% exhibits the highest hydrogen evolution rate, reaching 284.9 µmol·g-1·h-1. Moreover, this photocatalyst maintains robust photocatalytic stability even after three consecutive usage cycles. This study demonstrated that the Z-scheme CuInS2/ZnIn2S4 heterojunction photocatalyst exhibits enhanced hydrogen evolution efficiency, offering an effective structural design for harnessing solar energy to obtain hydrogen fuel. Therefore, this heterojunction photocatalyst is a promising candidate for practical applications in solar hydrogen production.

Effectiveness of a family empowerment program on caregiving capacity and adverse mood in caregivers of children with acute leukemia: a quasi-experimental study.

BACKGROUND: Family-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia. OBJECTIVE: To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia. METHODS: Sixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups. RESULTS: After 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P < 0.001), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the PPUS score of the intervention group was significantly lower than that of the control group (P < 0.05), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the SAS score of the intervention group was lower than that of the control group after intervention(P < 0.05), and the score difference before and after intervention was statistically significant (P < 0.001). CONCLUSION: Family empowerment program is beneficial in improving caregiving capacity and reducing disease uncertainty and anxiety among caregivers of children with acute leukemia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073476 2023-07-12 Retrospectively registered.

Emotion Dynamics among Late Adolescents and Emerging Adults: The Role of Maternal Privacy Invasion Perceptions.

Prior research suggests that youth experience immediate emotional distress following privacy invasion, but it is unclear whether and how persistent privacy invasion over longer periods destabilizes the intrapersonal emotional regulatory functions that privacy serves. This study investigated whether late adolescents and emerging adults who reported different patterns of maternal privacy invasion over a full academic year showed differences in emotion regulation, as reflected by the frequency and lability of negative and positive emotional experiences. Participants were first-year university students (n = 349; 60.2% female) in Hong Kong, aged 17 to 24 (MT1 = 18.20, SDT1 = 1.10). They self-reported maternal privacy invasion perceptions and negative and positive emotions 16 times, at bi-weekly intervals. Latent class growth analyses divided participants into a Higher Invasion Perceptions group (24.9%), a Moderate Invasion Perceptions group (46.4%), and a Lower Invasion Perceptions group (28.7%). A one-way MANCOVA examined potential differences in negative and positive emotion dynamics across groups, indexed by frequency (means) and instability (mean square of successive differences and probability of acute change). In line with predictions, both the Higher Invasion and Moderate Invasion groups reported higher negative emotion frequency and instability, compared to the Lower Invasion group. However, groups showed no significant differences regarding positive emotion frequency and instability. The findings indicate that perceptions of maternal privacy invasion predict youth's negative emotion regulation processes over their first collegiate year. Prolonged, higher levels of maternal privacy invasion may disrupt the intrapersonal regulatory functions that privacy serves over time.

Expression of myelin transcription factor 1 and lamin B receptor mediate neural progenitor fate transition in the zebrafish spinal cord pMN domain.

The pMN domain is a restricted domain in the ventral spinal cord, defined by the expression of the olig2 gene. Though it is known that the pMN progenitor cells can sequentially generate motor neurons and oligodendrocytes, the lineages of these progenitors are controversial and how their progeny are generated is not well understood. Using single-cell RNA sequencing, here, we identified a previously unknown heterogeneity among pMN progenitors with distinct fates and molecular signatures in zebrafish. Notably, we characterized two distinct motor neuron lineages using bioinformatic analysis. We then went on to investigate specific molecular programs that regulate neural progenitor fate transition. We validated experimentally that expression of the transcription factor myt1 (myelin transcription factor 1) and inner nuclear membrane integral proteins lbr (lamin B receptor) were critical for the development of motor neurons and neural progenitor maintenance, respectively. We anticipate that the transcriptome features and molecular programs identified in zebrafish pMN progenitors will not only provide an in-depth understanding of previous findings regarding the lineage analysis of oligodendrocyte progenitor cells and motor neurons but will also help in further understanding of the molecular programming involved in neural progenitor fate transition.

Phage-Displayed Nanobody as a Sensitive Nanoprobe to Enhance Chemiluminescent Immunoassay for Cronobacter sakazakii Detection in Dairy Products.

The exploitation of stable, high-affinity, and low-cost nanoprobes is essential to develop immunoassays for real-time monitoring of foodborne pathogens, so as to safeguard human health. The possible interaction of the Fc fragment of antibodies with spA protein on Staphylococcus aureus will result in unexpected interference. To address this consideration, we described herein for the first time the development of nanobodies that by definition are devoid of the Fc fraction. These nanobodies directed against Cronobacter sakazakii (C. sakazakii) were retrieved from a dedicated immune phage-displayed nanobody library. The binders showed superiority of low cost, strong stability, high binding affinity, and adequate load capacity. Thereafter, a phage-mediated sandwich enzyme-linked immunosorbent assay (ELISA) was constructed by using Cs-Nb2 as an antigen-capturing antibody and phage-displayed Cs-Nb1 as a detection probe. To further enhance the sensitivity, a chemiluminescent enzyme immunoassay (CISA) was established by replacing the substrate from 3,3',5,5'-tetramethylbenzidine (TMB) to luminol, providing a limit of detection of 1.04 × 104 CFU/mL, with a recovery of 98.15-114.63% for the detection of C. sakazakii in dairy products. The proposed nanobody-based phage-mediated sandwich CLISA shows various advantages, including high sensitivity, cost effectiveness, enhanced loading capacity of the enzyme, and high resistance to the matrix effect, providing a strategy for the design of immunoassays toward foodborne pathogens.

Enhancing Oriented Immobilization Efficiency: A One-for-Two Organism-Bispecific Nanobody Scaffold for Highly Sensitive Detection of Foodborne Pathogens.

Nanobodies have gained widespread application in immunoassays. However, their small size presents a significant challenge in achieving effective immobilization and optimal sensitivity. Here, we present a novel "one-for-two"-oriented immobilization platform based on an organism-bispecific nanobody (O-BsNb) scaffold, enabling highly sensitive detection of two bacterial pathogens. Through genetic engineering, a bispecific nanobody (BsNb) was engineered, targeting Salmonella spp. and Vibrio parahaemolyticus. The O-BsNb scaffold allowed one nanobody to bind specifically to inactivated bacteria, forming an organism-oriented immobilization platform, while the other served as the capture antibody. Consequently, the O-BsNb bioscaffold-based ELISA (O-ELISA) for individual detection of S. enteritidis and V. parahaemolyticus was established. When compared to the sandwich ELISA utilizing passive immobilization of monovalent nanobodies, the O-ELISA exhibited a remarkable 13.4- and 13.7-fold improvement in LOD for S. enteritidis and V. parahaemolyticus, respectively, highlighting the enhanced immobilization efficacy of the O-ELISA. Furthermore, the feasibility and reproducibility of the assay in practical samples were meticulously evaluated, revealing exemplary performance in terms of recovery precision and assay stability. These findings demonstrate the significant potential of the O-ELISA platform for the sensitive detection of macromolecules, opening new avenues for efficient pathogen identification in foodborne safety and clinical diagnostics.

New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue.

PURPOSE: During lung cancer surgery, it is very important to define tumor boundaries and determine the surgical margin distance. In previous research, systemically application of fluorescent probes can help medical professionals determine the boundaries of tumors and find small tumors and metastases, thereby improving the accuracy of surgical resection. However, there are very few safe and effective probes that can be applied to clinical trials up to now, which limits the clinical application of fluorescence imaging. Here we developed a new technology that can quickly identify the tumor area in the resected lung tissue during the operation and distinguish the tumor boundary and metastatic lymph nodes. EXPERIMENTAL DESIGN: For animal studies, a PDX model of lung cancer was established. The tumors, lungs, and peritumoral muscle tissues of tumor-bearing mice were surgically removed and incubated with a probe targeting epidermal growth factor receptor (EGFR) for 20 min, and then imaged by a closed-field near-infrared two-zone (NIR-II) fluorescence imaging system. For clinical samples, ten surgically removed lung tissues and 60 lymph nodes from 10 lung cancer patients undergoing radical resection were incubated with the targeting probe immediately after intraoperative resection and imaged to identify the tumor area and distinguish the tumor boundary and metastatic lymph nodes. The accuracy of fluorescence imaging was confirmed by HE staining and immunohistochemistry. RESULTS: The ex vivo animal imaging experiments showed a fluorescence enhancement of tumor tissue. For clinical samples, our results showed that this new technology yielded more than 85.7% sensitivity and 100% specificity in identifying the tumor area in the resected lung tissue. The average fluorescence tumor-to-background ratio was 2.5 ± 1.3. Furthermore, we also used this technique to image metastatic lymph nodes intraoperatively and showed that metastatic lymph nodes have brighter fluorescence than normal lymph nodes, as the average fluorescence tumor-to-background signal ratio was 2.7 ± 1.1. Calculations on the results of the fluorescence signal in relation to the number of metastatic lymph nodes yielded values of 77.8% for sensitivity and 92.1% for specificity. We expect this new technology to be a useful diagnostic tool for rapid intraoperative pathological detection and margin determination. CONCLUSIONS: By using fluorescently labeled anti-human EGFR recombinant antibody scFv fragment to incubate freshly isolated tissues during surgery, the probes can quickly accumulate in lung cancer tissues, which can be used to quickly identify tumor areas in the resected lung tissues and distinguish tumor boundaries and find metastases in lymph nodes. This technology is expected to be used for rapid intraoperative pathological detection and margin determination.

Association of Nonpuerperal Mastitis with Cytokines Related to Helper T Cells TH1/TH2 and TH17/Treg.

Objective: To investigate the association of nonpuerperal mastitis with cytokines related to the helper T cells TH1/TH2 and TH17/Treg and associated immune balance. Methods: From 2016 to 2021, we included 40 patients with non-puerperal mastitis who underwent surgery at China-Japan Friendship Hospital and compared them with 40 control patients with benign non-infectious breast disease. Hematoxylin-eosin staining detects inflammatory infiltrates of breast tissue. The expression of interferon γ and interleukin 4 in breast tissue was detected by immunofluorescence imaging, and the relative protein expression of TH1/TH2 and TH17/Treg cell-associated cytokines in CD4+ T cells was detected by western blotting. CD4+ T cells were isolated by fluorescence-activated cell sorting for detection of the relative protein expression of interferon γ and interleukin 4 in CD4+ T cells. Results: Hematoxylin-eosin staining showed that the nonpuerperal mastitis group had significantly greater inflammatory infiltration than the control group. Immunofluorescence images showed the relative fluorescence intensity of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative fluorescence intensity of interleukin 4 did not significantly differ between the 2 groups (P = .0686). Western blotting revealed that the relative protein expression of interferon γ, interleukin 2, and interleukin 17 was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 (P = .0512), interleukin 10 (P = .3088), and transforming growth factor ß (P = .0653) did not significantly differ between the 2 groups. Flow cytometry of isolated CD4+ T cells showed the relative protein expression of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 did not significantly differ between the 2 groups (P = .0680). Conclusion: The expression of the TH1 cytokines interferon γ and interleukin 2 and the TH17 cytokine interleukin 17 was significantly higher in patients with nonpuerperal mastitis, while the TH2 cytokine interleukin 4 and the Treg cytokines interleukin 10 and transforming growth factor ß were expressed at lower levels. This study provides new research ideas for the treatment of mastitis.

A modified extreme event-based synchronicity measure for climate time series.

Extreme event-based synchronicity is a specific measure of similarity of extreme event-like time series. It is capable to capture the nonlinear interactions between climatic extreme events. In this study, we proposed a modified extreme event-based synchronicity measure that incorporates two types of extreme events (positive and negative) simultaneously in climate anomalies to characterize the synchronization and time delays. Statistical significance of the modified extreme event synchronization measure is tested by Monte-Carlo simulations. The applications of the modified extreme event-based synchronicity measure on synthetic time series verified that it was superior to the traditional event synchronicity measure. Both synchronous and antisynchronous features between climate time series could be captured by the modified measure. It is potentially applied in investigating the interrelationship between climate extremes and climate index or constructing complex networks of climate variables. In addition, this modified extreme event-based synchronicity measure could be easily applied to other types of time series just by identifying the extreme events properly.

Expression of Phospholipase D Family Member 6 in Bovine Testes and Its Molecular Characteristics.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of reversed transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) found that the relative expression of the PLD6 gene in the testicular tissues of two-year-old Simmental calves was significantly higher than that of six-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker DEAD box helicase 4 (DDX4, also known as VASA). Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and the PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piwi-interacting RNA (piRNA) binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and piwi like RNA-mediated gene silencing 2 (PIWIL2). In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

The Synergistic Effect in CdS/g-C3N4 Nanoheterojunctions Improves Visible Light Photocatalytic Performance for Hydrogen Evolution Reactions.

This study focuses on the development of heterojunction photocatalysts for the efficient utilization of solar energy to address the energy crisis and reduce environmental pollution. Cadmium sulfide (CdS)/graphite-type carbon nitride (g-C3N4) nanocomposites were synthesized using a hydrothermal method, and their photoelectrochemical properties and photocatalytic performance for hydrogen evolution reaction (HER) were characterized. Scanning electron microscope images showed the intimate interface and caviar-like nanoheterojunction of the CdS nanoparticles on g-C3N4 nanospheres, suggesting their potential involvement in the photocatalytic process. Electrochemical and spectroscopic analyses were conducted to confirm the roles of CdS in the nanoheterojunction. The results showed that 10 wt% CdS/g-C3N4 nanospheres exhibited higher photocatalytic activity than pure g-C3N4 under visible light irradiation. A HER rate of 655.5 µmol/g/h was achieved after three photocatalytic cycles, signifying good photocatalytic stability. The synergistic effect of the Z-scheme heterojunction formed by g-C3N4 and CdS was identified as the main factor responsible for the enhanced photocatalytic performance and stability. The interface engineering effect of CdS/g-C3N4 facilitated the separation of photogenerated electrons and holes. This study provides insights into the design and fabrication of efficient HER photocatalysts.

Deep-learning-based automatic evaluation of rice seed germination rate.

BACKGROUND: Rice is an important food crop plant in the world and is also a model plant for genetics and breeding research. The germination rate is an important indicator that measures the performance of rice seeds. Currently, solutions involving image processing techniques have substantial challenges in the identification of seed germination. The detection of rice seed germination without human intervention involves challenges because the rice seeds are small and densely distributed. RESULTS: In this article, we develop a convolutional neural network (YOLO-r) that can detect the germination status of rice seeds and automatically evaluate the total number of germinations. Image partition, the Transformer encoder, a small target detection layer, and CDIoU loss are exploited in YOLO-r to improve the detection accuracy. A total of 21 429 seeds were collected, which have different phenotypic characteristics in length, shape, and color. The results show that the mean average precision of YOLO-r is 0.9539, which is higher than the compared models. Moreover, the average detection time per image of YOLO-r was 0.011 s, which meets the real-time requirements. The experimental results demonstrate that YOLO-r is robust to complex situations such as water stains, impurities, awns, adhesion, and so on. The results also show that the mean absolute error of the predicted germination rate mainly exists within 0.1. CONCLUSIONS: Numerous experimental studies have demonstrated that YOLO-r can predict rice germination rate in a fast, easy, and accurate manner. © 2022 Society of Chemical Industry.

Transforming the fermented fish landscape: Microbiota enable novel, safe, flavorful, and healthy products for modern consumers.

Regular consumption of fish promotes sustainable health while reducing negative environmental impacts. Fermentation has long been used for preserving perishable foods, including fish. Fermented fish products are popular consumer foods of historical and cultural significance owing to their abundant essential nutrients and distinct flavor. This review discusses the recent scientific progress on fermented fish, especially the involved flavor formation processes, microbial metabolic activities, and interconnected biochemical pathways (e.g., enzymatic/non-enzymatic reactions associated with lipids, proteins, and their interactions). The multiple roles of fermentation in preservation of fish, development of desirable flavors, and production of health-promoting nutrients and bioactive substances are also discussed. Finally, prospects for further studies on fermented fish are proposed, including the need of monitoring microorganisms, along with the precise control of a fermentation process to transform the traditional fermented fish to novel, flavorful, healthy, and affordable products for modern consumers. Microbial-enabled innovative fermented fish products that consider both flavor and health benefits are expected to become a significant segment in global food markets. The integration of multi-omics technologies, biotechnology-based approaches (including synthetic biology and metabolic engineering) and sensory and consumer sciences, is crucial for technological innovations related to fermented fish. The findings of this review will provide guidance on future development of new or improved fermented fish products through regulating microbial metabolic processes and enzymatic activities.

Defective AMPA-mediated synaptic transmission and morphology in human neurons with hemizygous SHANK3 deletion engrafted in mouse prefrontal cortex.

Genetic abnormalities in synaptic proteins are common in individuals with autism; however, our understanding of the cellular and molecular mechanisms disrupted by these abnormalities is limited. SHANK3 is a postsynaptic scaffolding protein of excitatory synapses that has been found mutated or deleted in most patients with 22q13 deletion syndrome and about 2% of individuals with idiopathic autism and intellectual disability. Here, we generated CRISPR/Cas9-engineered human pluripotent stem cells (PSCs) with complete hemizygous SHANK3 deletion (SHANK3+/-), which is the most common genetic abnormality in patients, and investigated the synaptic and morphological properties of SHANK3-deficient PSC-derived cortical neurons engrafted in the mouse prefrontal cortex. We show that human PSC-derived neurons integrate into the mouse cortex by acquiring appropriate cortical layer identities and by receiving and sending anatomical projections from/to multiple different brain regions. We also demonstrate that SHANK3-deficient human neurons have reduced AMPA-, but not NMDA- or GABA-mediated synaptic transmission and exhibit impaired dendritic arbors and spines, as compared to isogenic control neurons co-engrafted in the same brain region. Together, this study reveals specific synaptic and morphological deficits caused by SHANK3 hemizygosity in human cortical neurons at different developmental stages under physiological conditions and validates the use of co-engrafted control and mutant human neurons as a new platform for studying connectivity deficits in genetic neurodevelopmental disorders associated with autism.

A collagen-based bi-layered composite dressing for accelerated wound healing.

AIM OF THE STUDY: The aim of the study was to fabricate collagen-based composite dressings, evaluate the efficiency for wound healing and reveal the mechanism of promoting wound healing. MATERIALS AND METHODS: An innovative bi-layered composite wound dressing was developed using two marine biomacromolecules (collagen and chitosan). Full-thickness skin defect model was performed to evaluate the wound healing activity in vivo. The levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL-1, IL-6, IL-8) and growth factors like transforming growth factor beta (TGF-ß), vascular epidermal growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA assays. The total amount of collagen was quantified by hydroxyproline content. The proliferation and viability of fibroblast cells cultured on collagen sponges were determined by CCK-8 assay. RESULTS: The results of wound closure and histopathological analysis indicated that non-crosslinked collagen-based bi-layered composite dressing stimulated wound healing, accelerated re-epithelialization and accomplished wound healing within a time span of 28 days. The results of levels of inflammatory cytokines and growth factors showed that collagen-based composite dressings could reduce the inflammatory response and upregulate growth factors levels to accelerate the wound healing. The results of hydroxyproline content and CCK-8 assay indicated that collagen-based composite dressings could also promote collagen synthesis and fibroblasts viability and proliferation. CONCLUSION: The non-crosslinked collagen-based bi-layered composite dressing could be applied for an efficient and ideal wound dressing. Therefore, the findings provided the essential theoretical basis for the potential of collagen-based composite dressing applied in wound healing fields.

Response to 'Cesarean section or non-breastfeeding for prevention of MTCT - Beware of sending the wrong message'.

We are glad to respond to the concerns of Drs. Levy and Terrault about our articles on the mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in HBeAg-positive mothers. We agree with Drs. Levy and Terrault that antiviral therapy of HBV during pregnancy could effectively decrease the MTCT, and this strategy has been recommended by WHO for pregnant women with a high viral load. However, the long-term influences of the abrupt cessation of antiretroviral drugs in mothers and prenatal exposure to antiviral drugs in newborns are not completely understood and are still under investigation. And not all pregnant mothers would accept this regiment due to the medication availability and individual willingness. It makes sense to study the influential factors on MTCT among mothers with high-risk transmission but not taking antiviral drugs. Despite the relatively large number of subjects included in our cohort (N = 857), post hoc power computation shows that the test efficacy is far from adequate to detect the association between delivery mode or feeding type and HBV MTCT. Therefore, we summarized the relevant studies to reach a relatively reasonable conclusion in HBsAg- and HBeAg-positive pregnant mothers not taking antiviral drugs. We provide an alternative option for HBsAg- and HBeAg-positive pregnant mothers who cannot access or defer to antiviral therapy during pregnancy to reduce the risk of HBV transmission to their offspring.