Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

Control of Aluminum and Titanium Contents in the Electroslag Remelting of ATI 718PlusTM Alloy.

The burning loss of Al and Ti elements in superalloys during electroslag remelting has become a prevalent issue. And the existing slag system is not suitable for smelting the ATI 718PlusTM alloy. Therefore, it is imperative to develop a new slag system for smelting the ATI 718PlusTM alloy. To mitigate this issue, a thermodynamic model of the oxidation reaction of Al and Ti at the slag and alloy interface was established based on the ion and molecule coexistence theory (IMCT). The thermodynamic model was used to investigate the correlation between the equilibrium content of Al and Ti, slag composition, smelting temperature, and initial Al and Ti content of the electrode. The results indicate that while increasing the smelting temperature can effectively inhibit the burning loss of Al, it will exacerbate the burning loss of Ti. Increasing CaO and Al2O3 contents can inhibit the Al burning loss, while an increase in the TiO2 content can inhibit the Ti burning loss. Although an increase in the MgO content results in the burning loss of Al, its impact on the Al is minimal. The burning loss of Al and Ti was not affected by the change in the CaF2 content. The high Al content in ATI 718PlusTM makes it prone to burning loss of Al during the electroslag remelting. The combustion loss of Al can be reduced by increasing the Ti content in the electrode or adding a suitable amount of aluminum powder to the slag system. The accuracy of the model had been validated through experimental verification.

Crossbreeding Effect of Chalcogenation and Iodination on Benzene Additives Enables Optimized Morphology and 19.68% Efficiency of Organic Solar Cells.

Volatile solid additives have attracted increasing attention in optimizing the morphology and improving the performance of currently dominated non-fullerene acceptor-based organic solar cells (OSCs). However, the underlying principles governing the rational design of volatile solid additives remain elusive. Herein, a series of efficient volatile solid additives are successfully developed by the crossbreeding effect of chalcogenation and iodination for optimizing the morphology and improving the photovoltaic performances of OSCs. Five benzene derivatives of 1,4-dimethoxybenzene (DOB), 1-iodo-4-methoxybenzene (OIB), 1-iodo-4-methylthiobenzene (SIB), 1,4-dimethylthiobenzene (DSB) and 1,4-diiodobenzene (DIB) are systematically studied, where the widely used DIB is used as the reference. The effect of chalcogenation and iodination on the overall property is comprehensively investigated, which indicates that the versatile functional groups provided various types of noncovalent interactions with the host materials for modulating the morphology. Among them, SIB with the combination of sulphuration and iodination enabled more appropriate interactions with the host blend, giving rise to a highly ordered molecular packing and more favorable morphology. As a result, the binary OSCs based on PM6:L8-BO and PBTz-F:L8-BO as well as the ternary OSCs based on PBTz-F:PM6:L8-BO achieved impressive high PCEs of 18.87%, 18.81% and 19.68%, respectively, which are among the highest values for OSCs.

Layer-by-Layer Organic Solar Cells Enabled by 1,3,4-Selenadiazole-Containing Crystalline Small Molecule with Double-Fibril Network Morphology.

A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.

Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

Oral delivery of bacteria expressing wsv108 gene-specific dsRNA protects shrimp from white spot syndrome virus (WSSV) infection.

Double-stranded RNA (dsRNA) can specifically inhibit gene expression by RNA interference and has important application potential in animal disease control. White spot syndrome virus (WSSV) is one of the most harmful pathogens in shrimp aquaculture, causing huge economic losses every year. In this study, we investigated the function of the WSSV-encoded wsv108 protein. We demonstrated that wsv108 could promote apoptosis by interacting with heat shock protein 70 (HSP70) and enhancing the expression of multiple apoptosis-related genes. Silencing of wsv108 gene by injection with specific dsRNA prepared by in vitro transcription significantly increased the survival rate of WSSV-infected shrimp and reduced the viral load in tissues, suggesting that wsv108 is important for WSSV pathogenicity. Based on this, we expressed the wsv108 specific dsRNA in engineered Escherichia coli. Oral feeding of this bacterium could inhibit the expression of wsv108, increase the survival rate of WSSV-infected shrimp, and decrease the viral load of WSSV in tissues. Therefore, this study developed a new method for treatment of WSSV disease by oral administration of bacterially expressed dsRNA against a novel therapeutic target molecule, which could be a potential candidate strategy for WSSV control in aquaculture.

Ca2+/calmodulin-mediated desensitization of glutamate receptors shapes plant systemic wound signalling and anti-herbivore defence.

Plants rely on systemic signalling mechanisms to establish whole-body defence in response to insect and nematode attacks. GLUTAMATE RECEPTOR-LIKE (GLR) genes have been implicated in long-distance transmission of wound signals to initiate the accumulation of the defence hormone jasmonate (JA) at undamaged distal sites. The systemic signalling entails the activation of Ca2+-permeable GLR channels by wound-released glutamate, triggering membrane depolarization and cytosolic Ca2+ influx throughout the whole plant. The systemic electrical and calcium signals rapidly dissipate to restore the resting state, partially due to desensitization of the GLR channels. Here we report the discovery of calmodulin-mediated, Ca2+-dependent desensitization of GLR channels, revealing a negative feedback loop in the orchestration of plant systemic wound responses. A CRISPR-engineered GLR3.3 allele with impaired desensitization showed prolonged systemic electrical signalling and Ca2+ waves, leading to enhanced plant defence against herbivores. Moreover, this Ca2+/calmodulin-mediated desensitization of GLR channels is a highly conserved mechanism in plants, providing a potential target for engineering anti-herbivore defence in crops.

18.6% Efficiency All-Polymer Solar Cells Enabled by a Wide Bandgap Polymer Donor Based on Benzo[1,2-d:4,5-d']bisthiazole.

The limited selection of wide bandgap polymer donors for all-polymer solar cells (all-PSCs) is a bottleneck problem restricting their further development and remains poorly studied. Herein, a new wide bandgap polymer, namely PBBTz-Cl, is designed and synthesized by bridging the benzobisthiazole acceptor block and chlorinated benzodithiophene donor block with thiophene units for application as an electron donor in all-PSCs. PBBTz-Cl not only possesses wide bandgap and deep energy levels but also displays strong absorption, high-planar structure, and good crystallinity, making it a promising candidate for application as a polymer donor in organic solar cells. When paired with the narrow bandgap polymer acceptor PY-IT, a fibril-like morphology forms, which facilitates exciton dissociation and charge transport, contributing to a power conversion efficiency (PCE) of 17.15% of the corresponding all-PSCs. Moreover, when introducing another crystalline polymer acceptor BTP-2T2F into the PBBTz-Cl:PY-IT host blend, the absorption ditch in the range of 600-750 nm is filled, and the blend morphology is further optimized with the trap density reducing. As a result, the ternary blend all-PSCs achieve a significantly improved PCE of 18.60%, which is among the highest values for all-PSCs to date.

Tailored Succinic Acid-Derived Molecular Structures toward 25.41%-Efficiency and Stable Perovskite Solar Cells.

Minimizing interfacial charged traps in perovskite films is crucial for reducing the non-radiative recombination and improving device performance. In this study, succinic acid (SA) derivatives varying active sites and spatial configurations are designed to modulate defects and crystallization in perovskite film. The SA derivative with two symmetric Br atoms, dibromosuccinic acid (DBSA), exhibits the optimal spatial arrangement for defect passivation. Experimental and theoretical results indicate that the carboxyl group and atomic Br in DBSA synergistically interact with the under-coordinated Pb2+ . Moreover, the strong electronegativity of Br efficiently stabilizes the formamidinium cation via electrostatic interaction. Consequently, film quality is significantly improved and non-radiative recombination is markedly depressed, resulting in a photoluminesence lifetime of exceeding 4 µs of and a carrier diffusion length of 3 µm. An exceptional efficiency of 25.41% (certified at 25.00%) along with a high fill factor of 84.39% and excellent long-term operational stability have been achieved finally.

Personalized and privacy-preserving federated heterogeneous medical image analysis with PPPML-HMI.

Heterogeneous data is endemic due to the use of diverse models and settings of devices by hospitals in the field of medical imaging. However, there are few open-source frameworks for federated heterogeneous medical image analysis with personalization and privacy protection without the demand to modify the existing model structures or to share any private data. Here, we proposed PPPML-HMI, a novel open-source learning paradigm for personalized and privacy-preserving federated heterogeneous medical image analysis. To our best knowledge, personalization and privacy protection were discussed simultaneously for the first time under the federated scenario by integrating the PerFedAvg algorithm and designing the novel cyclic secure aggregation with the homomorphic encryption algorithm. To show the utility of PPPML-HMI, we applied it to a simulated classification task namely the classification of healthy people and patients from the RAD-ChestCT Dataset, and one real-world segmentation task namely the segmentation of lung infections from COVID-19 CT scans. Meanwhile, we applied the improved deep leakage from gradients to simulate adversarial attacks and showed the strong privacy-preserving capability of PPPML-HMI. By applying PPPML-HMI to both tasks with different neural networks, a varied number of users, and sample sizes, we demonstrated the strong generalizability of PPPML-HMI in privacy-preserving federated learning on heterogeneous medical images.

19.32% Efficiency Polymer Solar Cells Enabled by Fine-Tuning Stacking Modes of Y-Type Molecule Acceptors: Synergistic Bromine and Fluorine Substitution of the End Groups.

The success of Y6-type nonfullerene small molecule acceptors (NF-SMAs) in polymer solar cells (PSCs) can be attributed to their unique honeycomb stacking style, which leads to favorable thin-film morphologies. The intermolecular interactions related to the crystallization tendency of these NF-SMAs is closely governed by their electron accepting end groups. For example, the high performance Y6 derivative L8-BO (BTP-4F) presents three types of stacking modes in contrast to two stacking modes of Y6. Hence, it is ultimately interesting to obtain more insight on the packing properties and the preferences influenced by chemical modifications such as end group engineering. This work designs and synthesizes asymmetric and symmetric L8-BO derivatives with brominated end groups and explores the stacking preferences in various modes. The asymmetric BTP-3FBr displays an optimized crystallization tendency and thin film morphology, leading to a decent power conversion efficiency (PCE) of 18.34% in binary devices and a top PCE of 19.32% in ternary devices containing 15 wt% IDIC as the second acceptor.

Molecular mechanism of the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells.

IMPORTANCE: Viruses are able to mimic the physiological or pathological mechanism of the host to favor their infection and replication. Virus-mock basement membrane (VMBM) is a Megalocytivirus-induced extracellular structure formed on the surface of infected cells and structurally and functionally mimics the basement membrane of the host. VMBM provides specific support for lymphatic endothelial cells (LECs) rather than blood endothelial cells to adhere to the surface of infected cells, which constitutes a unique phenomenon of Megalocytivirus infection. Here, the structure of VMBM and the interactions between VMBM components and LECs have been analyzed at the molecular level. The regulatory effect of VMBM components on the proliferation and migration of LECs has also been explored. This study helps to understand the mechanism of LEC-specific attachment to VMBM and to address the issue of where the LECs come from in the context of Megalocytivirus infection.

Basigin binds bacteria and activates Dorsal signaling to promote antibacterial defense in Penaeus vannamei.

The NF-κB pathway plays an important role in immune regulation. Basigin, an immunoglobulin superfamily membrane protein, is involved in the activation of NF-κB. However, its role in NF-κB signaling in response to pathogen infection remains unclear. In this study, we identified the Basigin gene from Pacific white shrimp, Penaeus vannamei, a representative species for studying the innate immune system of invertebrates. Basigin promoted the degradation of the IκB homolog Cactus, facilitated the nuclear translocation of the NF-κB family member Dorsal, and positively regulated the expression of Dorsal pathway downstream antimicrobial peptide genes. Interestingly, recombinant Basigin protein could bind a variety of Gram-positive and Gram-negative bacteria. Silencing of Basigin inhibited the Dorsal signaling activated by V. parahaemolyticus infection and significantly decreased the survival rate of V. parahaemolyticus-infected shrimp. The expression levels of the antimicrobial peptides ALF1 and ALF2 were downregulated, and the phagocytosis of hemocytes was attenuated in Basigin-silenced shrimp. Similar results were observed in shrimp treated with a recombinant extracellular region of the Basigin protein that was able to compete with endogenous Basigin. Therefore, to the best of our knowledge, this study is the first to demonstrate the function of Basigin as a pathogen recognition receptor that activates NF-κB signaling for antibacterial immunity in shrimp.

High-Performance Nonfused Electron Acceptor with Precisely Controlled Side Chain Fluorination.

Modification of the molecular packing of nonfullerene acceptors through fluorination represents one of the most promising strategies to achieve highly efficient organic solar cells (OSCs). In this work, three nonfused electron acceptors, namely, DTCBT-Fx (x = 0, 5, 9) with precisely controlled amounts of fluorine atoms in the side chains are designed and synthesized, and the effect of side chain fluorination is systematically studied. The results demonstrate that the light absorption, energy levels, molecular ordering, and film morphology could be effectively tuned by precisely controlling the side chain fluorination. DTCBT-F5 with an appropriate fluorine functionalization exhibits suitable miscibility with the donor polymer (PM6), leading to diminished charge recombination and improved charge carrier mobility. Consequently, a promising power conversion efficiency of 12.7% was obtained for DTCBT-F5-based solar cells, which outperforms those OSCs based on DTCBT-F0 (11.4%) and DTCBT-F9 (11.6%), respectively. This work demonstrates that precise control of the fluorine functionalization in side chains of nonfused electron acceptors is an effective strategy for realizing highly efficient OSCs.

Repetitive DNA sequence detection and its role in the human genome.

Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, and structural characteristics of repeats. Besides, we introduced diverse biological functions of repeats and reviewed existing methods for automatic repeat detection, classification, and masking. Finally, we analyzed the type, structure, and regulation of repeats in the human genome and their role in the induction of complex diseases. We believe that this review will facilitate a comprehensive understanding of repeats and provide guidance for repeat annotation and in-depth exploration of its association with human diseases.

Structure Influence of Amine-Containing Additives on the Solution State and Out-of-Plane Conductivity of PEDOT:PSS for Efficient Organic Solar Cells.

Additives are extensively explored for improving PEDOT:PSS performances mainly through the removal of excess PSS and as a secondary dopant. In this work, amine-containing additives are introduced to PEDOT:PSS solutions as processing additives where the interactions to the PSS are anticipated through electrostatic interactions. Such interactions affected solution property where the increased viscosity is found to significantly increase the out-of-plane conductivity of the PEDOT:PSS thin films. Organic solar cells adopting these additive-assisted processed PEDOT:PSS layers as hole transporting layers (HTL) showed the improved device performances that resulted from the reduced series resistance provided by the PEDOT:PSS HTL. A top power conversion efficiency of 18.28% is achieved with para-phenylenediamine (PPD) additive in the PEDOT:PSS HTL, which is 3.5% higher compared to devices with neat PEDOT:PSS thin film as the HTL.

Synergy effects of copper ion in doxorubicin-based chelate prodrug for cancer chemo-chemodynamic combination therapy.

Doxorubicin (DOX) is a commonly studied chemotherapeutic agent for the treatment of solid tumors, but the severe side effects limit its clinical application. It is shown that DOX-metal chelate has lower in vitro cytotoxicity compared with DOX, as the anthracyclines of DOX can form coordinative interaction with transition metal ions. In addition, the transition metal ions could catalyze the production of hydroxyl radicals (·OH) via Fenton/Fenton-like reactions to achieve antitumor chemodynamic therapy (CDT). In this study, copper ions (Cu2+) were applied to obtain DOX/Cu(II) prodrug, and a liposomal formulation was used to avoid the rapid blood clearance and optimize the biodistribution of this prodrug. In vitro and in vivo antitumor results demonstrated that this pH sensitive Cu-chelating prodrug can reduce adverse effects of DOX but improve the antitumor efficiency due to the combination of chemotherapy and chemodynamic therapy. Our study provided a facile and effective approach of metal-chelating prodrug strategy for combination cancer therapy strategy.

The Hippo-Yki pathway downstream transcription factor Scalloped negatively regulates immune defense against Vibrio parahaemolyticus infection in shrimp.

The Hippo-Yki signaling pathway plays a crucial role in numerous biological processes. Previous studies have demonstrated the significance of signal transduction components of the Hippo pathway in the immune response of shrimp. In this study, the downstream transcription factor of Hippo signaling, Scalloped, was analyzed in the context of Vibrio parahaemolyticus infection in Pacific white shrimp, Penaeus vannamei. Upon bacterial and fungal infections, the expression of Scalloped was upregulated in hemocytes. Scalloped was found to localize in the nucleus and interact with the Hippo pathway downstream transcriptional co-activator Yki. With the assistance of Yki, Scalloped activated the promoter of Cactus, a cytoplasmic inhibitor of the NF-κB pathway, leading to the inhibition of the nuclear translocation of the NF-κB family member Dorsal in shrimp. By inhibiting the Dorsal pathway, Scalloped reduced the expression of immune functional proteins and negatively regulated the immune response against bacterial infection in shrimp. RNAi-mediated silencing of Scalloped significantly enhanced the survival rate of V. parahaemolyticus-infected shrimp and reduced the bacterial load in tissues. These findings demonstrate the potential of Scalloped as a therapeutic target for vibriosis in crustaceans and contribute to our understanding of the shrimp's antibacterial defense and the functional roles of Hippo signaling in animal immunity.