DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke.

N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extrasynaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292-1304 (NR2B(CT)). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2B(CT) that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca(2+) influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extrasynaptic sites and this interaction acts as a central mediator for stroke damage.

Hitchhiking of Cas9 with nucleus-localized proteins impairs its controllability and leads to efficient genome editing of NLS-free Cas9.

CRISPR-Cas9 is the most commonly used genome-editing tool in eukaryotic cells. To modulate Cas9 entry into the nucleus to enable control of genome editing, we constructed a light-controlled CRISPR-Cas9 system to control exposure of the Cas9 protein nuclear localization signal (NLS). Although blue-light irradiation was found to effectively control the entry of Cas9 protein into the nucleus with confocal microscopy observation, effective gene editing occurred in controls with next-generation sequencing analysis. To further clarify this phenomenon, a CRISPR-Cas9 editing system without the NLS and a CRISPR-Cas9 editing system containing a nuclear export signal were also constructed. Interestingly, both Cas9 proteins could achieve effective editing of target sites with significantly reduced off-target effects. Thus, we speculated that other factors might mediate Cas9 entry into the nucleus. However, NLS-free Cas9 was found to produce effective target gene editing even following inhibition of cell mitosis to prevent nuclear import caused by nuclear membrane disassembly. Furthermore, multiple nucleus-localized proteins were found to interact with Cas9, which could mediate the "hitchhiking" of NLS-free Cas9 into the nucleus. These findings will inform future attempts to construct controllable gene-editing systems and provide new insights into the evolution of the nucleus and compatible protein functions.

2D Tellurium Films Based Self-Drive Near Infrared Photodetector.

To reduce the amount of energy consumed in integrated circuits, high efficiency with the lowest energy is always expected. Self-drive device is one of the options in the pursuit of low power nanodevices. It is a typical strategy to form an internal electric field by constructing a heterojunction in self-drive semiconductor system. Here, a two-step method is proposed to prepare high quality centimeter-sized 2D tellurium (Te) thin film with hall mobility as high as 37.3 cm2 V-1 s-1, and the 2D Te film is further assembled with silicon to form a heterojunction for self-drive photodetector, which can realize effective detection from visible to near infrared bands. The photodetectivity of the heterojunctions can reach 1.58×1011 Jones under the illumination of 400 nm@ 1.615 mW/cm2 and 2.08×108 Jones under the illumination of 1550 nm@ 1.511 mW/cm2 without bias. Our experiments demonstrate the potential of 2D tellurium thin films for wide band and near infrared integrated device applications.

Thermal Conductivity of the Graphene/Polydimethylsiloxane Composite by Manipulating the Network Structure.

In this work, a nonequilibrium molecular dynamics simulation is utilized to explore the effect of network structure of graphene (GE) on the thermal conductivity of the GE/polydimethylsiloxane (PDMS) composite. First, the thermal conductivity of composites rises with increasing volume fraction of GE. The heat transfer ability via the GE channel is found to be nearly the same by analyzing the GE-GE interfacial thermal resistance (ITR). More heat energy is transferred via the GE channel at the high volume fraction of GE by calculating the GE heat transfer ratio, which leads to the high thermal conductivity. Then, the thermal conductivity of composites rises with increasing stacking area between GE, which is attributed to both the strong heat transfer ability via the GE channel and the high GE heat transfer ratio. Following it, the thermal conductivity of composites first rises and then drops down with increasing defect density for a single vacancy defect while it continuously increases for a single void defect. The heat transfer ability between GE is enhanced due to the formation of interlayer covalent bonds. However, the intrinsic thermal conductivity of GE is significantly reduced for a single vacancy defect while it remains relatively well for a single void defect. As a result, the GE heat transfer ratio is maximum at the intermediate defect density for a single vacancy defect while it rises monotonically for a single void defect, which can rationalize the thermal conductivity. Meanwhile, the relationship between ITR and the number of covalent bonds can be described by an empirical equation. Finally, the thermal conductivity for the stacked structure is larger than that for the noncontact structure or the intersected structure. In summary, this work provides a clear and novel understanding of how the network structure of GE influences the thermal conductivity of the GE/PDMS composite.

A regulation strategy of self-assembly molecules for achieving efficient inverted perovskite solar cells.

Self-assembled monolayers (SAMs) have been successfully employed to enhance the efficiency of inverted perovskite solar cells (PSCs) and perovskite/silicon tandem solar cells due to their facile low-temperature processing and superior device performance. Nevertheless, depositing uniform and dense SAMs with high surface coverage on metal oxide substrates remains a critical challenge. In this work, we propose a holistic strategy to construct composite hole transport layers (HTLs) by co-adsorbing mixed SAMs (MeO-2PACz and 2PACz) onto the surface of the H2O2-modified NiOx layer. The results demonstrate that the conductivity of the NiOx bulk phase is enhanced due to the H2O2 modification, thereby facilitating carrier transport. Furthermore, the hydroxyl-rich NiOx surface promotes uniform and dense adsorption of mixed SAM molecules while enhancing their anchoring stability. In addition, the energy level alignment at the interface is improved due to the utilization of mixed SAMs in an optimized ratio. Furthermore, the perovskite film crystal growth is facilitated by the uniform and dense composite HTLs. As a result, the power conversion efficiency of PSCs based on composite HTLs is boosted from 22.26% to 23.16%, along with enhanced operational stability. This work highlights the importance of designing and constructing NiOx/SAM composite HTLs as an effective strategy for enhancing both the performance and stability of inverted PSCs.

Formimidoyltransferase cyclodeaminase prevents the starvation-induced liver hepatomegaly and dysfunction through downregulating mTORC1.

The liver is a crucial center in the regulation of energy homeostasis under starvation. Although downregulation of mammalian target of rapamycin complex 1 (mTORC1) has been reported to play pivotal roles in the starvation responses, the underpinning mechanisms in particular upstream factors that downregulate mTORC1 remain largely unknown. To identify genetic variants that cause liver energy disorders during starvation, we conduct a zebrafish forward genetic screen. We identify a liver hulk (lvh) mutant with normal liver under feeding, but exhibiting liver hypertrophy under fasting. The hepatomegaly in lvh is caused by enlarged hepatocyte size and leads to liver dysfunction as well as limited tolerance to starvation. Positional cloning reveals that lvh phenotypes are caused by mutation in the ftcd gene, which encodes the formimidoyltransferase cyclodeaminase (FTCD). Further studies show that in response to starvation, the phosphorylated ribosomal S6 protein (p-RS6), a downstream effector of mTORC1, becomes downregulated in the wild-type liver, but remains at high level in lvh. Inhibition of mTORC1 by rapamycin rescues the hepatomegaly and liver dysfunction of lvh. Thus, we characterize the roles of FTCD in starvation response, which acts as an important upstream factor to downregulate mTORC1, thus preventing liver hypertrophy and dysfunction.

ZrTe2 Compound Dirac Semimetal Contacts for High-Performance MoS2 Transistors.

Recent investigations reveal elemental semimetal (Bi and Sb) contacts fabricated with conventional deposition processes exhibit a remarkable capacity of approaching the quantum limit in two-dimensional (2D) semiconductor contacts, implying it might be an optimal option to solve the contact issue of 2D semiconductor electronics. Here, we demonstrate novel compound Dirac semimetal ZrTe2 contacts to MoS2 constructed by a nondestructive van der Waals (vdW) transfer process, exhibiting excellent ohmic contact characteristics with a negligible Schottky barrier. The band hybridization between ZrTe2 and MoS2 was verified. The bilayer MoS2 transistor with a 250 nm channel length on a 20 nm thick hexagonal boron nitride (h-BN) exhibits an ION/IOFF current ratio over 105 and an on-state current of 259 µA µm-1. The current results reveal that 2D compound semimetals with vdW contacts can offer a diverse selection of proper semimetals with adjustable work functions for the next-generation 2D-based beyond-silicon electronics.

The enhancement of explosive power contributes to the development of anaerobic capacity: A comparison of autoregulatory progressive resistance exercise and velocity-based resistance training.

Objectives: Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

Asymmetric Modification of Carbazole Based Self-Assembled Monolayers by Hybrid Strategy for Inverted Perovskite Solar Cells.

Carbazole-based self-assembled molecules (SAMs) are widely applied in inverted perovskite solar cells (iPSCs) due to their unique molecular properties. However, the symmetrical structure of the carbazole-based SAMs makes it difficult to finely regulate their performance, which impedes the further enhancement of the efficiency and stability of iPSCs. This work shows that by building an asymmetric carbazole core, the crucial properties of SAM molecules can be effectively regulated. It has been confirmed that the hybrid thieno[2,3-b]thiophene unit of this asymmetric core governs the energy level, the surface wettability, and the defect passivation capability of the SAMs, while the substituent of core has a greater impact on the molecular dipole and device stability. The synergistic effects from thieno[2,3-b]thiophene and fluorine lead to the KF-derived iPSC demonstrating a certified power conversion efficiency (PCE) of 25.17% and excellent operational stability. This hybrid design concept offers a promising approach for the further structural modification of SAMs in iPSCs.

Cancer-associated fibroblasts contribute to the immunosuppressive landscape and influence the efficacy of the combination therapy of PD-1 inhibitors and antiangiogenic agents in hepatocellular carcinoma.

BACKGROUND: Chronic inflammation is considered the most critical predisposing factor of hepatocellular carcinoma (HCC), with inflammatory cell heterogeneity, hepatic fibrosis accumulation, and abnormal vascular proliferation as prominent features of the HCC tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) play a key role in HCC TME remodeling. Therefore, the level of abundance of CAFs may significantly affect the prognosis and outcome in HCC patients. METHODS: Unsupervised clustering was performed based on 39 genes related to CAFs in HCC identified by single-cell RNA sequencing data. Patients of bulk RNA were grouped into CAF low abundance cluster and high abundance clusters. Subsequently, prognosis, immune infiltration landscape, metabolism, and treatment response between the two clusters were investigated and validated by immunohistochemistry. RESULTS: Patients in the CAF high cluster had a higher level of inflammatory cell infiltration, a more significant immunosuppressive microenvironment, and a significantly worse prognosis than those in the low cluster. At the metabolic level, the CAF high cluster had lower levels of aerobic oxidation and higher angiogenic scores. Drug treatment response prediction indicated that the CAF high cluster could have a better response to PD-1 inhibitors and conventional chemotherapeutic agents for HCC such as anti-angiogenic drugs, whereas CAF low cluster may be more sensitive to transarterial chemoembolization treatment. CONCLUSIONS: This study not only revealed the TME characteristics of HCC with the difference in CAF abundance but also further confirmed that the combination therapy of PD-1 inhibitors and anti-angiogenic drugs may be more valuable for patients with high CAF abundance.

MATE transporter GFD1 cooperates with sugar transporters, mediates carbohydrate partitioning and controls grain-filling duration, grain size and number in rice.

More than half of the world's food is provided by cereals, as humans obtain >60% of daily calories from grains. Producing more carbohydrates is always the final target of crop cultivation. The carbohydrate partitioning pathway directly affects grain yield, but the molecular mechanisms and biological functions are poorly understood, including rice (Oryza sativa L.), one of the most important food sources. Here, we reported a prolonged grain filling duration mutant 1 (gfd1), exhibiting a long grain-filling duration, less grain number per panicle and bigger grain size without changing grain weight. Map-based cloning and molecular biological analyses revealed that GFD1 encoded a MATE transporter and expressed high in vascular tissues of the stem, spikelet hulls and rachilla, but low in the leaf, controlling carbohydrate partitioning in the stem and grain but not in the leaf. GFD1 protein was partially localized on the plasma membrane and in the Golgi apparatus, and was finally verified to interact with two sugar transporters, OsSWEET4 and OsSUT2. Genetic analyses showed that GFD1 might control grain-filling duration through OsSWEET4, adjust grain size with OsSUT2 and synergistically modulate grain number per panicle with both OsSUT2 and OsSWEET4. Together, our work proved that the three transporters, which are all initially classified in the major facilitator superfamily family, could control starch storage in both the primary sink (grain) and temporary sink (stem), and affect carbohydrate partitioning in the whole plant through physical interaction, giving a new vision of sugar transporter interactome and providing a tool for rice yield improvement.

Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell population in breast tumors. A functionally diverse population of CAFs increases the dynamic complexity of the tumor microenvironment (TME). The intertwined network of the TME facilitates the interaction between activated CAFs and breast cancer cells, which can lead to the proliferation and invasion of breast cells. Considering the special transmission function of CAFs, the aim of this review is to summarize and highlight the crosstalk between CAFs and breast cancer cells in the TME as well as the relationship between CAFs and extracellular matrix (ECM), soluble cytokines, and other stromal cells in the metastatic state. The crosstalk between cancer-associated fibroblasts and tumor microenvironment also provides a plastic therapeutic target for breast cancer metastasis. In the course of the study, the inhibitory effects of different natural compounds on targeting CAFs and the advantages of different drug combinations were summarized. CAFs are also widely used in the diagnosis and treatment of breast cancer. The cumulative research on this phenomenon supports the establishment of a targeted immune microenvironment as a possible breakthrough in the prevention of invasive metastasis of breast cancer.

Clinical characteristics of three distinct types of pancreatitis with overlapping etiologies: A ten-year retrospective cohort study.

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed in non-HTG-induced acute pancreatitis (AP), such as in the early stage of acute biliary pancreatitis (ABP). There is overlap in the etiologies of ABP, HTG-AP, and biliary-hypertriglyceridemia acute pancreatitis (BHAP), which may be perplexing for clinicians. METHODS: We retrospectively analyzed 394 AP patients. The patients were divided into three groups based on etiology. We analyzed the differences among the three groups of patients in terms of general information, laboratory parameters, and prognosis. RESULTS: The mean age of patients in the ABP group was significantly higher than that in the HTG-AP and BHAP groups (p < 0.001). Females made up a greater percentage of the ABP group, whereas males made up the majority in the HTG-AP and BHAP groups. The ABP group had the highest PCT, AMS, LPS, ALT, AST, GGT, TBIL, DBIL, APACHE II, and BISAP scores. TG and BMI were highest in the HTG-AP group. AST and GGT levels were substantially greater in BHAP patients than those in HTG-AP. The BHAP group had the greatest incidence of organ failure, systemic complications, and local complications. CONCLUSION: ABP usually develops in people aged 50-59 years. HTG-AP primarily affects people aged 30-39 years. However, the peak incidence age of BHAP falls between the two aforementioned age groups (40-49 years). We also found that patients with BHAP seem to be in an intermediate state in terms of some biochemical markers and demographic characteristics. Furthermore, BHAP may have the worst clinical outcomes compared with HTG-AP and ABP.

Manipulating the Thermal Conductivity of the Graphene/Poly(vinyl alcohol) Composite via Surface Functionalization: A Multiscale Simulation.

The reverse non-equilibrium molecular dynamics simulation is used to investigate the influence of functional groups (FGs) on the thermal conductivity of a graphene/poly(vinyl alcohol) (PVA) composite, which considers non-polar (methyl) and polar (hydroxyl, amino, and carboxyl) groups. First, the polar groups can be more effective to improve the interfacial thermal conductivity than the non-polar group. This can be explained well by characterizing the interfacial Coulombic energy, number and lifetime of hydrogen bonds, vibrational density of states, and integrated autocorrelation of the interfacial heat power. Moreover, the hydroxyl group can improve the interfacial thermal conductivity more than the other groups, which can be rationalized by analyzing the surface roughness of graphene and the radial distribution function of FGs and the PVA chains. However, the introduction of FGs destroys the graphene structure, which consequently reduces the intrinsic thermal conductivity. Furthermore, by adopting the effective medium approximation model and finite element method, there exists a critical graphene length where the overall thermal conductivities are equal for the functionalized and pristine graphene. Finally, the distribution state of graphene is emphasized to be more vital in determining the overall thermal conductivity than the generally accepted interfacial thermal conductivity.

FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation.

FBXW2 is a poorly characterized F-box protein, as a tumor suppressor that inhibits growth and metastasis of lung cancer by promoting ubiquitylation and degradation of oncogenic proteins, including SKP2 and ß-catenin. However, what the biological functions of FBXW2 in prostate cancer cells and whether FBXW2 targets other substrates to involve in progression of prostate cancer is still unclear. Here, we reported that overexpression of FBXW2 attenuated proliferation and metastasis of PCa models both in vitro and in vivo, while FBXW2 depletion exhibited the opposite effects. Intriguingly, FBXW2 was an E3 ligase for EGFR in prostate cancer. EGFR protein level and its half-life were extended by FBXW2 depletion, while EGFR protein level was decreased, and its half-life was shortened upon overexpression of FBXW2, but not its dominant-negative mutant. Importantly, FBXW2 bond to EGFR via its consensus degron motif (TSNNST), and ubiquitylated and degraded EGFR, resulting in repression of EGF function. Thus, our data uncover a novel that FBXW2 as a tumor suppressor of prostate cancer, inhibits EGFR downstream by promoting EGFR ubiquitination and degradation, resulting in repression of cell proliferation and metastasis.

Production and characterization of monoclonal antibodies against mandarinfish ranavirus and first identification of pyloric caecum as the major target tissue.

Mandarinfish ranavirus (MRV), also known as a variant of largemouth bass virus (LMBV), is an emerging pathogen in mandarinfish aquaculture. In this study, monoclonal antibodies (mAbs) against MRV were produced and characterized, and 7 mAbs were obtained through Western blotting screening and all 7 mAbs specifically recognized MRV/LMBV but not several piscine iridoviruses as ISKNV, GIV and TFV. By LC MS/MS analysis, the recognized viral proteins by seven mAbs were identified as MRV-pORF47L, MRV-pORF55R, MRV-pORF57L, MRV-pORF77L and MRV-pORF78L, respectively, and all five viral proteins are late expression structural proteins by Western blotting. Based on mAb 1C4, immuno-histochemistry and immuno-histo-fluorescence were performed to re-assess the tissue tropism of MRV. The result showed that abundant reactive signals were observed in infected spleen, kidney as well as intestine and pyloric caecum. Real-time quantitative PCR also demonstrated that spleen as well as pyloric caecum and intestines are the major target tissue upon MRV infection. In infected intestines and pyloric caecum, numerous enlarged, multinucleated cells with intracytoplasmic inclusions were identified as the target cells of MRV, suggesting that MRV serves as a digestive tract pathogen to mandarinfish, which may explain why acute infection of MRV can cause the typical clinicopathology featured by severe ascites.

Graph Sampling-Based Multi-Stream Enhancement Network for Visible-Infrared Person Re-Identification.

With the increasing demand for person re-identification (Re-ID) tasks, the need for all-day retrieval has become an inevitable trend. Nevertheless, single-modal Re-ID is no longer sufficient to meet this requirement, making Multi-Modal Data crucial in Re-ID. Consequently, a Visible-Infrared Person Re-Identification (VI Re-ID) task is proposed, which aims to match pairs of person images from the visible and infrared modalities. The significant modality discrepancy between the modalities poses a major challenge. Existing VI Re-ID methods focus on cross-modal feature learning and modal transformation to alleviate the discrepancy but overlook the impact of person contour information. Contours exhibit modality invariance, which is vital for learning effective identity representations and cross-modal matching. In addition, due to the low intra-modal diversity in the visible modality, it is difficult to distinguish the boundaries between some hard samples. To address these issues, we propose the Graph Sampling-based Multi-stream Enhancement Network (GSMEN). Firstly, the Contour Expansion Module (CEM) incorporates the contour information of a person into the original samples, further reducing the modality discrepancy and leading to improved matching stability between image pairs of different modalities. Additionally, to better distinguish cross-modal hard sample pairs during the training process, an innovative Cross-modality Graph Sampler (CGS) is designed for sample selection before training. The CGS calculates the feature distance between samples from different modalities and groups similar samples into the same batch during the training process, effectively exploring the boundary relationships between hard classes in the cross-modal setting. Some experiments conducted on the SYSU-MM01 and RegDB datasets demonstrate the superiority of our proposed method. Specifically, in the VIS→IR task, the experimental results on the RegDB dataset achieve 93.69% for Rank-1 and 92.56% for mAP.

Modeling the power system resilience in China under different natural disasters.

A good understanding of the power system resilience is necessary for optimizing the investment strategies and supporting the emergency rescue, but the existing quantitative estimation results based on real outage events are still lacked due to the data limitations. Therefore, this study first establishes a unified framework to measure the power system resilience under different natural disasters, by integrating the electricity performance curve with the dynamic inoperability input-output model. Then, a database of 285 Chinese historical big power outage events caused by natural disasters is established, and the city-level power system resilience values are estimated. Finally, a benefit analysis is conducted for improving the power system resilience. Our major findings are that: (1) Electricity system recoveries quickest from hail (23.05 h), while restores slowest from snowstorm (117.31 h). (2) China's city electricity system is the most resilient to the thunderstorm, while is the least resilient to the earthquake. (3) Enhancing the power system resilience will significantly reduce the requirements for rescue resources, and the saved emergency rescue cost ranges from 0.57 million yuan to 12.08 million yuan with 1% reduction of initial inoperability.

Benzothieno[3,2-b]thiophene-Based Noncovalent Conformational Lock Achieves Perovskite Solar Cells with Efficiency over 24.

Organic semiconductors with noncovalently conformational locks (OSNCs) are promising building blocks for hole-transporting materials (HTMs). However, lack of satisfied neighboring building blocks negatively impacts the optoelectronic properties of OSNCs-based HTMs and imperils the stability of perovskite solar cells (PSCs). To address this limitation, we introduce the benzothieno[3,2-b]thiophene (BTT) to construct a new OSNC, and the resulting HTM ZS13 shows improved intermolecular charge extraction/transport properties, proper energy level, efficient surface passivation effect. Consequently, the champion devices based on doped ZS13 yield an efficiency of 24.39 % and 20.95 % for aperture areas of 0.1 and 1.01 cm2 , respectively. Furthermore, ZS13 shows good thermal stability and the capability of inhibiting I- ion migration, thus, leading to enhanced device stability. The success in neighboring-group engineering can triggered a strong interest in developing thienoacene-based OSNCs toward efficient and stable PSCs.

Combined overexpression of four transcription factors promotes effector T cell dedifferentiation toward early phenotypes.

Effector T cells, which are abundant but are short-lived after reinfusion into the body, are generally used for T-cell therapy, and antitumor immunity is typically not maintained over the long term. Genetic modification by early differentiated T cells and reinfusion has been shown to enhance antitumor immunity in vivo. This study overexpressed the characteristic transcription factors of differentiated early T cells by transfecting effector T cells with transcription factor recombinant lentivirus (S6 group: BCL6, EOMES, FOXP1, LEF1, TCF7, KLF7; S1 group: BCL6, EOMES, FOXP1, KLF7; S3 group: BCL6, EOMES, FOXP1, LEF1) to induce a sufficient number of effector T cells to dedifferentiate and optimize the transcription factor system. The results revealed that overexpression of early characteristic transcription factors in effector T cells upregulated the expression of early T cell differentiation markers (CCR7 and CD62L), with the S1 group having the highest expression level, while the rising trend of late differentiation marker (CD45RO) expression was suppressed. Moreover, the expression of early differentiation-related genes (ACTN1, CERS6, BCL2) was significantly increased, while the expression of late differentiation-related genes (KLRG-1) and effector function-related genes (GNLY, GZMB, PRF1) was significantly decreased; this difference in expression was more significant in the S1 group than in the other two experimental groups. The antiapoptotic ability of each experimental group was significantly enhanced, while the secretion ability of TNF-α and IFN-γ was weakened, with the effector cytokine secretion ability of the S1 group being the weakest. Transcriptomic analysis showed that the gene expression profile of each experimental group was significantly different from that of the control group, with differences in the gene expression pattern and number of differentially expressed genes in the S1 group compared with the other two experimental groups. The differentially expressed gene enrichment pathways were basically related to the cell cycle, cell division, and immune function. In conclusion, overexpression of early characteristic transcription factors in effector T cells induces their dedifferentiation, and induction of dedifferentiation by the S1 group may be more effective.