Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design.

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on-going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi-branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3-symmetrical A3-(D-core) architecture with a dipolar donor-acceptor (D-A) photochrome in each branch. Our design couples multi-dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal-recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA-doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi-dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate-determining thermal cyclization, while the branched and non-planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene-based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high-yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time-temperature indicators, optical logic encryption and multi-levelled data encryption.

Saturated Linkers in Two-Dimensional Covalent Organic Frameworks Boost Their Luminescence.

The development of highly luminescent two-dimensional covalent organic frameworks (COFs) for sensing applications remains challenging. To suppress commonly observed photoluminescence quenching of COFs, we propose a strategy involving interrupting the intralayer conjugation and interlayer interactions using cyclohexane as the linker unit. By variation of the building block structures, imine-bonded COFs with various topologies and porosities are obtained. Experimental and theoretical analyses of these COFs disclose high crystallinity and large interlayer distances, demonstrating enhanced emission with record-high photoluminescence quantum yields of up to 57% in the solid state. The resulting cyclohexane-linked COF also exhibits excellent sensing performance for the trace recognition of Fe3+ ions, explosive and toxic picric acid, and phenyl glyoxylic acid as metabolites. These findings inspire a facile and general strategy to develop highly emissive imine-bonded COFs for detecting various molecules.

Cutting COF-like C4 N to Give Colloidal Quantum Dots: Towards Optical Encryption and Bidirectional Sulfur Chemistry via Functional Group and Edge Effects.

Herein, we report the first synthesis of colloidal C4 N quantum dots (QDs) and their functional composites and explore their optical activities and edge-selective polysulfide adsorption-catalysis. As-obtained C4 NQDs are rich in carbonyl groups and edges, allowing good solution processability and facile assembly with other moieties for creating functionalities. While C4 NQDs show normal fluorescence (FL), the QD/poly(vinyl alcohol) (PVA) composites give FL/room-temperature-phosphorescence (RTP) dual-mode emission, enabling the corresponding solution to be used as an encryption ink. The QDs anchored onto carbon nanotubes can be used as a barrier layer to decorate commercial separators, endowing a Li-S cell with excellent cycling stability, high rate capability, and large areal capacity. Computation and experiment studies show that edge sites in C4 N favor polysulfide adsorption and catalysis and the enriched edges and carbonyl groups in QDs synergically promotecatalytic conversion of sulfur species.

Octupolar Acrylonitrile-Bridged 2D-Conjugated Polymers Enable Bright Far-Red Emission with Intense Two-Photon Absorption via Alkoxylation Chemistry.

Herein, alkoxylation chemistry is introduced as a "one-stone-three-birds" solution for exploring a new family of highly-fluorescent octupolar 2D-conjugated organic polymers/frameworks (OCOPs/OCOFs) combining far-red emission, high fluorescence quantum yield (QY), and strong two-photon absorption (TPA). Both alkoxy-substituted OCOP and OCOF comprising acrylonitrile-bridged strongly-coupled donor3-(acceptor core) chromophores densely packed in either disordered or ordered forms, exhibit significantly redshifted emission. They produce high QY of 22.2% and 27.8% in tetrahydrofuran, large TPA cross section of 600 and 1124 GM, and 2-3 folds and 15-30 folds that of non-alkoxylate amorphous counterpart respectively. Combined theoretical and experimental studies reveal unique "one-stone-three-birds" role of the alkoxylation in realizing red-shifted-emission, improved QY and TPA enabled by inducing steric hindrance effect for weakened π-π stacking, and triggering p-π conjugation effect for electronically engineering octupolar chromophores, while the crystalline engineering enables enforced coplanarity conformation and improved π-electron delocalization for further improved QY and TPA. The robust and biocompatible pentoxy-substituted polymer can be used not only as metal-free red-emissive phosphor for efficient warm white light-emitting diodes, but also as efficient two-photon fluorescence probes for bio-imaging.

Capturing Visible Light in Low-Band-Gap C4 N-Derived Responsive Bifunctional Air Electrodes for Solar Energy Conversion and Storage.

We report facile synthesis of low-band-gap mesoporous C4 N particles and their use as responsive bifunctional oxygen catalysts for visible-light-sensitive (VLS) rechargeable Zn-air battery (RZAB) and polymer-air battery (RPAB). Compared to widely studied g-C3 N4 , C4 N shows a smaller band gap of 1.99 eV, with a larger photocurrent response, and it can function as visible-light-harvesting antenna and bifunctional oxygen reduction/evolution (ORR/OER) catalysts, enabling effective photocoupling to tune oxygen catalysis. The C4 N-enabled VLS-RZAB displays a low charge voltage of 1.35 V under visible light, which is below the theoretical RZAB voltage of 1.65 V, corresponding to a high energy efficiency of 97.78 %. Pairing a C4 N cathode with a polymer anode also endows an VLS-RPAB with light-boosted charge performance. It is revealed that the ORR and OER active sites in C4 N are separate carbon sites near pyrazine-nitrogen atoms and photogenerated energetic holes can activate OER for improved reaction kinetics.

Versatile, Aqueous Soluble C2N Quantum Dots with Enriched Active Edges and Oxygenated Groups.

C2N has emerged as a new family of promising two-dimensional (2D) layered frameworks in both fundamental studies and potential applications. Transforming bulk C2N into zero-dimensional quantum dots (QDs) could induce unique quantum confinement and edge effects that produce improved or new properties. Despite their appealing potential, C2NQDs remain unexplored, and their intriguing properties and a fundamental understanding of their prominent edge effects are still not well understood. Here, we report the first synthesis of water-soluble C2NQDs via a top-down approach without any foreign stabilizer and exploit their linear/nonlinear optical properties and unique edge-preferential electrocatalytic activity toward polysulfides for versatile applications. The resultant dispersant-free C2NQDs with an average size of less than 5 nm feature rich oxygen-carrying groups and active edges, not only enabling excellent dispersion in water but also creating interesting multifunctionality. They can emit not only blue one-photon luminescence (OPL) under ultraviolet (UV) excitation but also green two-photon luminescence (TPL) with a wide near-infrared (NIR) excitation range of 750-900 nm, enabling their use as a new fluorescent ink. Interestingly, when C2NQDs are introduced to modify commercial separators, they can function as new metal-free catalysts to boost polysulfide redox kinetics and endow Li-S batteries with excellent cycling stability, high rate capability, and large areal capacity (7.0 mA h cm-2) at a high sulfur loading of 8.0 mg cm-2. Detailed theoretical and experimental results indicate that the edge of C2N is more favorable for trapping and catalyzing the polysulfide conversion than the terrace and that the synergy between the active edges and oxygenated groups enriched in C2NQDs remarkably improves polysulfide immobilization and catalytic conversion.

Ultrathin Black Phosphorus-on-Nitrogen Doped Graphene for Efficient Overall Water Splitting: Dual Modulation Roles of Directional Interfacial Charge Transfer.

Few-layered exfoliated black phosphorus (EBP) has attracted surging interest for electronics, optoelectronics, and catalysis. As compared to excellent progress in electronic and optoelectronic applications, very few reports are available for electrocatalysis by metal-free EBPs. Herein, we couple solution-processable ultrathin EBP nanosheets with higher Fermi level of N-doped graphene (NG) into a new metal-free 2D/2D heterostructure (EBP@NG) with well-designed interfaces and unique electronic configuration, as efficient and durable bifunctional catalysts toward hydrogen evolution and oxygen evolution reactions (HER/OER) for overall water splitting in alkaline media. By rational interface engineering, the synergy of EBP and NG is fully exploited, which not only improves the stability of EBP, but also effectively modulates electronic structures of each component to boost their intrinsic activities. Specifically, due to the lower Fermi level of EBP relative to NG, their electronic interaction induces directional interfacial electron transfer, which not only enriches the electron density over EBP and optimizes H adsorption/desorption to promote HER, but also introduces abundant positively charged carbon sites on NG and provides favorable formation of key OER intermediates (OOH*) to improve OER energetics. Thus, despite that pure EBP or NG alone has poor or negligible activity, EBP@NG achieves remarkably enhanced bifunctional HER/OER activities, along with an excellent durability. This endows an optimized electrolyzer using EBP@NG as anode and cathode with a low cell voltage of 1.54 V at 10 mA cm-2, which is smaller than that of the costly integrated Pt/C@RuO2 couple (1.60 V).

Mechanistic insights into the allosteric regulation of Pseudomonas aeruginosa aspartate kinase.

In plants and microorganisms, aspartate kinase (AK) catalyzes an initial commitment step of the aspartate family amino acid biosynthesis. Owing to various structural organizations, AKs from different species show tremendous diversity and complex allosteric controls. We report the crystal structure of AK from Pseudomonas aeruginosa (PaAK), a typical α2ß2 hetero-tetrameric enzyme, in complex with inhibitory effectors. Distinctive features of PaAK are revealed by structural and biochemical analyses. Essentially, the open conformation of Lys-/Thr-bound PaAK structure clarifies the inhibitory mechanism of α2ß2-type AK. Moreover, the various inhibitory effectors of PaAK have been identified and a general amino acid effector motif of AK family is described.

Donor-Acceptor Nanocarbon Ensembles to Boost Metal-Free All-pH Hydrogen Evolution Catalysis by Combined Surface and Dual Electronic Modulation.

A combined surface and dual electronic modulation strategy is used to realize metal-free all-pH catalysis towards the hydrogen evolution reaction (HER) by coupling a N-doped carbon framework (MHCF, electron acceptors) derived from MOFs with higher-Fermi-level pure carbon nanotubes (CNTs, electron donors), followed by surface modification with carboxyl-group-rich polymers. Although the three constituents are inactive, as-assembled ternary membranes yield superior HER performance with low overpotentials and high durability (≤5 % activity loss over 100 h) at all pH values. The C adjacent to pyrrolic N in MHCF is the most active site and the induced directional interfacial electron transfer from CNTs to MHCF coupled with N-driven intramolecular electron transfer in MHCF optimizes Gibbs free energy for hydrogen adsorption (ΔGH* ) near zero, while the polymer modulation enables local H+ enrichment in acidic media and enhanced water adsorption and activation in neutral and basic media.

AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.

Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.

PCDH11X mutation as a potential biomarker for immune checkpoint therapies in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have achieved impressive success in lung adenocarcinoma (LUAD). However, the response to ICIs varies among patients, and predictive biomarkers are urgently needed. PCDH11X is frequently mutated in LUAD, while its role in ICI treatment is unclear. In this study, we curated genomic and clinical data of 151 LUAD patients receiving ICIs from three independent cohorts. Relations between PCDH11X and treatment outcomes of ICIs were examined. A melanoma cohort collected from five published studies, a pan-cancer cohort, and non-ICI-treated TCGA-LUAD cohort were also examined to investigate whether PCDH11X mutation is a specific predictive biomarker for LUAD ICI treatment. Among the three ICI-treated LUAD cohorts, PCDH11X mutation (PCDH11X-MUT) was associated with better clinical response compared to wild-type PCDH11X (PCDH11X-WT). While in ICI-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and the non-ICI-treated TCGA-LUAD cohort, no significant differences in overall survival (OS) were observed between the PCDH11X-MUT and PCDH11X-WT groups. PCDH11X mutation was associated with increased PD-L1 expression, tumor mutation burden (TMB), neoantigen load, DNA damage repair (DDR) mutations, and hot tumor microenvironment in TCGA-LUAD cohort. Our findings suggested that the PCDH11X mutation might serve as a specific biomarker to predict the efficacy of ICIs for LUAD patients. Considering the relatively small sample size of ICI-treated cohorts, future research with larger cohorts and prospective clinical trials will be essential for validating and further exploring the role of PCDH11X mutation in the context of immunotherapy outcomes in LUAD. KEY MESSAGES: PCDH11X mutation is associated with better clinical response compared to wild type PCDH11X in three ICIs-treated LUAD cohorts. In ICIs-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and non-ICIs-treated TCGA-LUAD cohorts PCDH11X mutation is not associated with better clinical response, suggesting PCDH11X mutation might be a specific biomarker to predict the efficacy of ICIs treatment for LUAD patients. PCDH11X mutation is associated with increased PD-L1 expression, tumor mutation burden, and neoantigen load in TCGA-LUAD cohort. PCDH11X mutation is associated with hot tumor microenvironment in TCGA-LUAD cohort.

Treating solid tumors with TCR-based chimeric antigen receptor targeting extra domain B-containing fibronectin.

BACKGROUND: The suppression of chimeric antigen receptor (CAR) T cells by the tumor microenvironment (TME) is a crucial obstacle in the T-cell-based treatment of solid tumors. Extra domain B (EDB)-fibronectin is an oncofetal antigen expressed on the endothelium layer of the neovasculature and cancer cells. Though recognized as a T cell therapy target, engineered CAR T cells thus far have failed to demonstrate satisfactory in vivo efficacy. In this study, we report that targeting EDB-fibronectin by redirected TCR-CAR T cells (rTCR-CAR) bypasses the suppressive TME for solid tumor treatment and sufficiently suppressed tumor growth.We generated EDB-targeting CAR by fusing single-chain variable fragment to CD3ε, resulting in rTCR-CAR. Human primary T cells and Jurkat cells were used to study the EDB-targeting T cells. Differences to the traditional second-generation CAR T cell in signaling, immune synapse formation, and T cell exhaustion were characterized. Cytotoxicity of the rTCR-CAR T cells was tested in vitro, and therapeutic efficacies were demonstrated using xenograft models. METHODS: RESULTS: In the xenograft models, the rTCR-CAR T cells demonstrated in vivo efficacies superior to that based on traditional CAR design. A significant reduction in tumor vessel density was observed alongside tumor growth inhibition, extending even to tumor models established with EDB-negative cancer cells. The rTCR-CAR bound to immobilized EDB, and the binding led to immune synapse structures superior to that formed by second-generation CARs. By a mechanism similar to that for the conventional TCR complex, EDB-fibronectin activated the rTCR-CAR, resulting in rTCR-CAR T cells with low basal activation levels and increased in vivo expansion. CONCLUSION: Our study has demonstrated the potential of rTCR-CAR T cells targeting the EDB-fibronectin as an anticancer therapeutic. Engineered to possess antiangiogenic and cytotoxic activities, the rTCR-CAR T cells showed therapeutic efficacies not impacted by the suppressive TMEs. These combined characteristics of a single therapeutic agent point to its potential to achieve sustained control of solid tumors.

Circulating cell-free DNA sequencing for early detection of lung cancer.

INTRODUCTION: Lung cancer is a leading cause of death in patients with cancer. Early diagnosis is crucial to improve the prognosis of patients with lung cancer. Plasma circulating cell-free DNA (cfDNA) contains comprehensive genetic and epigenetic information from tissues throughout the body, suggesting that early detection of lung cancer can be done non-invasively, conveniently, and cost-effectively using high-sensitivity techniques such as sequencing. AREAS COVERED: In this review, we summarize the latest technological innovations, coupled with next-generation sequencing (NGS), regarding genomic alterations, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer, as well as their clinical advances. Additionally, we discuss the suitability of study designs for diagnostic accuracy evaluation for different target populations and clinical questions. EXPERT OPINION: Currently, cfDNA-based early screening and diagnosis of lung cancer faces many challenges, such as unsatisfactory performance, lack of quality control standards, and poor repeatability. However, the progress of several large prospective studies employing epigenetic features has shown promising predictive performance, which has inspired cfDNA sequencing for future clinical applications. Furthermore, the development of multi-omics markers for lung cancer, including genome-wide methylation and fragmentomics, is expected to play an increasingly important role in the future.

Mucin-fused myeloid-derived growth factor (MYDGF164) exhibits a prolonged serum half-life and alleviates fibrosis in chronic kidney disease.

BACKGROUND AND PURPOSE: Although no effective therapy is available to stop or reverse CKD progression targeting its key feature, the loss of peritubular capillaries (PTCs) leading to interstitial fibrosis, myeloid-derived growth factor (MYDGF) with tissue-repairing activities enlightens its therapeutic potential for CKD. However, the extremely short circulatory lifetime (15 min) restricts its application. EXPERIMENTAL APPROACH: We selected a tandem repeated (TR) region of human CD164 as a carrier to fuse with MYDGF and then investigated for biophysical and pharmacokinetic changes. The MYDGF164 bioactivities were validated in HUVECs and then assessed in HK-2 cells. We also investigated its efficacy in unilateral ureteral obstruction (UUO)-treated mice and in adenine-induced CKD rats. KEY RESULTS: MYDGF164 was modified with sialoglycans, improving its resistance to serum proteases and increasing its hydrodynamic radius. The half-life of MYDGF164 was significantly prolonged but retained its original cell proliferation, anti-apoptosis, and tubulogenesis activities. It selectively stimulated the proliferation in endothelial and epithelial cells through phosphorylating MAPK1/3. MYDGF164 alleviated capillary rarefaction, hypoxia, renal fibrosis, and tubular atrophy in UUO mice and in adenine-induced CKD rats. MYDGF164 restored renal function, with normalized creatinine and urea levels in adenine-induced CKD rats. Histopathology and immunohistochemistry revealed that MYDGF164 protection was related to its cell-proliferative, anti-apoptosis, and angiogenesis activities. CONCLUSIONS AND IMPLICATIONS: This study is the first successful example of using a tandem repeated region of hCD164 as a cargo protein for the pharmacokinetic improvement of therapeutic proteins. Our findings highlight the potential of MYDGF164 in alleviating renal fibrosis in CKD.

Development and validation of a blood-based genomic mutation signature to predict the clinical outcomes of atezolizumab therapy in NSCLC.

OBJECTIVES: We designed this study to develop a blood-based genomic mutation signature (bGMS) model for predicting the efficacy of atezolizumab therapy in non-small cell lung cancer (NSCLC) in a non-invasive manner. MATERIALS AND METHODS: Patients with NSCLC treated with atezolizumab from POPLAR and OAK clinical trials were included in our study. OAK cohort was defined as the training group, and POPLAR cohort was defined as the validation group. LASSO Cox regressions were applied to the training group to develop the gene mutation signature model to predict the overall survival (OS). Then the model was validated in the validation group. The combined impact of bGMS and other factors was explored with multivariable Cox regression. RESULTS: A bGMS risk model including 15 genes was established to classify patients into high-bGMS and low-bGMS groups. High-bGMS patients had shorter overall survival (OS) and progression-free survival (PFS) compared with low-bGMS in both training cohort (OS 7.9 vs. 19.9 months, p < 0.0001; PFS 1.7 vs. 4 months, p = 0.011) and validation cohort (OS 8.4 vs. 18.6 months, p = 0.0019; PFS 1.5 vs. 4.4 months, p = 0.013). The bGMS was superior to the blood tumor mutation burden (bTMB), LAF-bTMB, MSAF, PD-L1 expression, and a 5-genomic mutation signature in predicting OS for patients receiving atezolizumab. In addition, low-bGMS patients receiving atezolizumab therapy had a better OS rate compared with those receiving docetaxel therapy in both training (P < 0.0001) and validation groups (P = 0.018). Multivariate Cox regression analysis showed that bGMS was an independent prognostic factor on OS and PFS for patients receiving atezolizumab. Furthermore, a nomogram was developed to combine bGMS with the clinical characteristics to improve the predictive power further. CONCLUSION: bGMS could predict OS benefit for patients with NSCLC receiving atezolizumab therapy. BGMS and other non-invasive clinical characteristics can be combined to develop a more accurate model.

A Systematic Review of Systematic Reviews on Blended Learning: Trends, Gaps and Future Directions.

Blended Learning (BL) is one of the most used methods in education to promote active learning and enhance students' learning outcomes. Although BL has existed for over a decade, there are still several challenges associated with it. For instance, the teachers' and students' individual differences, such as their behaviors and attitudes, might impact their adoption of BL. These challenges are further exacerbated by the COVID-19 pandemic, as schools and universities had to combine both online and offline courses to keep up with health regulations. This study conducts a systematic review of systematic reviews on BL, based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to identify BL trends, gaps and future directions. The obtained findings highlight that BL was mostly investigated in higher education and targeted students in the first place. Additionally, most of the BL research is coming from developed countries, calling for cross-collaborations to facilitate BL adoption in developing countries in particular. Furthermore, a lack of ICT skills and infrastructure are the most encountered challenges by teachers, students and institutions. The findings of this study can create a roadmap to facilitate the adoption of BL. The findings of this study could facilitate the design and adoption of BL which is one of the possible solutions to face major health challenges, such as the COVID-19 pandemic.

Over-Expression and Prognostic Significance of FATP5, as a New Biomarker, in Colorectal Carcinoma.

Background: Fatty acid transporters (FATPs) family play an important role in the uptake and metabolism regulation of long-chain fatty acids, which influence the occurrence and developing of multiple tumors. Fatty acid transporter 5(FATP5), a member of FATPs family, participates in fatty acid transport and lipid metabolism and is related to tumor development, whose mechanism in colorectal cancer (CRC) remains unclear. Methods: In this study, we comprehensively utilized a range of relevant bioinformatic tools along with multiple databases to analyze the expression of FATPs family and investigate the biological function and prognostic value of FATP5 in CRC. Besides, cell proliferation and cell cycle distribution analysis, western blotting and immunohistochemistry (IHC) further validated the conclusion of bioinformatics analysis. Results: FATP5 is the only member of FATPs family which was overexpressed in CRC. In the survival analysis based on the GSE39582 databases, the low expression of FATP5 predicts poor prognosis in CRC. Similar results were also observed in GSE17536, GSE28814 and TCGA colon cohorts. The potential function of DNA methylation regulated the abnormal expression of FATP5 in CRC. In addition, enrichment analysis indicated that FATP5 also participates in the regulation of cell cycle. Furthermore, Gene Set Enrichment Analysis (GSEA) showed a strong negative correlation between FATP5 and cell growth, implying that it may participate in regulating cancer cell proliferation by the regulation of cell cycle G2/M transition. At last, we identified that FATP5 was overexpressed in colorectal carcinoma tissues through immunohistochemistry staining, and played an important role in cell cycle by cell proliferation and cell cycle distribution analysis. Conclusion: This study suggested that FATP5 was overexpression in colorectal carcinoma and predicted favorable prognosis, indicating it as a novel appealing prognostic marker for CRC.

Amniotic mesenchymal stem cells derived hepatocyte-like cells attenuated liver fibrosis more efficiently by mixed-cell transplantation.

BACKGROUND: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for liver fibrosis. However, only a small portion of the transplanted cells propagated in the recipient liver. AIM: We hypothesized that the efficiency of cell therapy could be improved by transplanting amniotic mesenchymal stem cells (AMSCs) derived HLCs along with human umbilical vein endothelial cells (HUVECs) and undifferentiated AMSCs. METHODS: Briefly, we used a two-step protocol to generate induced HLCs. We confirmed organoids formation of HLCs in 3D collagen scaffolds with HUVECs and AMSCs. To determine whether the HLCs can migrate into the liver tissue and perform in vivo function, we transplanted the cells to mice with liver fibrosis. RESULTS: Co-culture of HLCs with HUVECs and AMSCs demonstrated improved function of HLCs within the organoids. Furthermore, transplantation using non-homogeneous cells, i.e. HLCs mixed with HUVECs and AMSCs, exhibited better graft survival in the host animals with liver fibrosis. Our experiment results suggested that compared to mock transplantation or HLCs transplantation groups, liver fibrosis was reduced significantly in mixed-cell groups. The AST levels in the plasma of transplanted mice were markedly decreased only in the mixed-cell transplantation group. The engraftment of HLCs in mice liver was better in mixed-cell transplantation group, compared with HLCs-only transplantation group. CONCLUSIONS: The HLCs attenuated liver fibrosis more efficiently when transplanted along with HUVECs and AMSCs, and this suggested that we could improve the efficiency of cell therapy by transplanting functional cells partially along with stromal cells.

Alkene-Linked Covalent Organic Frameworks Boosting Photocatalytic Hydrogen Evolution by Efficient Charge Separation and Transfer in the Presence of Sacrificial Electron Donors.

Covalent organic frameworks (COFs) are potential photocatalysts for artificial photosynthesis but they are much less explored for photocatalytic hydrogen evolution (PHE). COFs, while intriguing due to crystallinity, tunability, and porosity, tend to have low apparent quantum efficiency (AQE) and little is explored on atomistic structure-performance correlation. Here, adopting triphenylbenzene knots and phenyl linkers as a proof of concept, three structurally related COFs with different linkages are constructed to achieve a tunable COF platform and probe the effect of the linkage chemistry on PHE. Cyano-substituted alkene-linked COF (COF-alkene) yields a stable 2330 µmol h-1 g-1 PHE rate, much superior to imine- and imide-linked counterparts (<40 µmol h-1 g-1) under visible light irradiation. Impressively, COF-alkene achieves an AQE of 6.7% at 420 nm. Combined femtosecond transient absorption spectroscopy and theoretical calculation disclose the critical role of cyano-substituted alkene linkages toward high efficiency of charge separation and transfer in the presence of sacrificial electron donors-the decisive key to the superior PHE performance. Such alkene linkages can also be extended to design a series of high-performance polymeric photocatalysts, highlighting a general design idea for efficient PHE.

Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors.

Purpose: Given that heterogeneous expression and variants of antigens on solid tumors are responsible for relapse after chimeric antigen receptor (CAR)-T cell therapy, we hypothesized that combinatorial targeting two tumor-associated antigens would lessen this problem and enhance the antitumor activity of T cells. Methods: The co-expression level of CD70 and B7-H3 was analyzed in multiple tumor tissue samples. Further, two putative antigens were identified in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis database. Two CD70 targeted CARs with different antigen binding domain, truncated CD27 and CD70 specific single-chain antibody fragment (scFv), were designed to screen a more suitable target-antigen binding moiety. Accordingly, we designed a bivalent tandem CAR (TanCAR) and further assessed the anti-tumor efficacy of TanCAR-T cells in vitro and in vivo. Results: Our results indicated that co-expression of CD70 and B7-H3 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma as well as melanoma. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70+ tumor cells. TanCAR-T cells induced enhanced ability of cytolysis and cytokine release over unispecific CAR-T cells when encountering tumor cells expressing two target-antigens. Further, low doses of TanCAR-T cells could also effectively control the lung cancer and melanoma xenografts and improved overall survival of the treated animals. Conclusion: TanCAR-T cells targeting CD70 and B7-H3 exhibit enhanced antitumor functionality and improve the problem of antigenic heterogeneity and variant in the treatment against solid tumor and melanoma.