Enhanced rheology and firefighting performance of fluorine-free soft foams through the assembly of cellulose nanofibres and cellulose nanocrystals at the air-liquid interface.

In this work, we developed soft and highly stable perfluorocarbon-free foams based on cellulose nanofibres (CNFs), cellulose nanocrystals (CNCs) and alkyl polyglycoside (APG). Neither the CNCs nor the CNFs can effectively stabilise the APG foam, which is reflected in the spontaneous degradation of the foam. Interestingly, blending these two nanocelluloses and foaming resulted in an ultrastable foam. The reflective optical interference technique was used to visualise liquid flow in the liquid film, and the results showed that the foam film with a thickness of only a few tens of nanometres gained excellent mechanical stability by tuning the assembly of CNCs and CNFs at the air-liquid interface. Moreover, the interfibril interactions at the Plateau borders reduce the bubble coarsening rate and drainage rate. In pool fire extinguishing tests, increasing the total concentration of CNCs and CNFs improved the foam stability, but increasing the viscosity led to a decrease in the foam spreading rate. Thus, a formulation with 0.4 % nanocellulose has poorer firefighting performance than a formulation with 0.15 % nanocellulose. When the ratios of CNCs and CNFs are properly controlled, the burnback performance of perfluorocarbon-free foam is better than that of state-of-the-art fluorinated AFFFs for n-heptane pool fires. The sustainability of the firefighting process is considerably improved by switching to the nonperfluorinated liquid foam developed in this work.

CoFe Oxides-Coated 2D Black Phosphorus for Flame-Retardant Nanocoatings with Tunable Mechanical Strength and Efficient Elimination of Toxic Gases.

2D black phosphorus (BP) degrades irreversibly into phosphate compounds under ambient conditions, which limits its application in a variety of fields. In this study, by coating amorphous ferric-cobalt oxides (CoFeO) on BP nanosheets, a multifunctional CoFeO@2D BP is successfully developed that effectively inhibited combustion and catalyzed CO oxidation to eliminate toxic gases. Strong affinity between transition-metal cations and BP allowed the uniform growth of amorphous ferric‒cobalt oxides on the BP surface, which effectively prevented the spontaneous degradation of 2D BP. By combining CoFeO@2D BP with gelatin and kosmotropic salts, the as-obtained nanocoatings are used for surface treatment of flammable polyurethane foam (PU). Kosmotropic ions induced strong hydrophobic interactions and bundling within the gelatin chains which significantly enhanced the mechanical performance of the PU. BP accelerates the carbonization of gelatin to inhibit the combustion of PU, and CoFe oxides, which act as true active centers to accelerate the oxidation of CO, effectively inhibiting the production of harmful gas. The release rate of CO decreases by 73% and the limiting oxygen index (LOI) increases from 17% to ≈32% during PU combustion. The developed novel 2D material opens the way for multifunctional coatings with integrated durability, flame retardancy, and high smoke suppression efficiency.

Hierarchical 2D/1D MOFs/electrospun ZIF-67 modified carbon nanofibers heterostructure electrode for high-performance asymmetric supercapacitor.

In this paper, a 2 dimensional (2D) metal-organic frameworks (MOFs) nanosheets grown on 1D ZIF-67 modified carbon nanofibers (CNFs) was designed and fabricated with a hierarchical heterostructure. The hierarchical 2D/1D MOFs/CCNF offers rich electrochemical active sites and favorable ion/electron diffusion pathways. The synergistic effect of Co, CNFs and MOFs from heterostructures contributes to superb electrochemical activities. Benefiting from the hierarchical heterostructures optimized by the mass ratio of ZIF-67/PAN and CCNF/NiMOF as well as the type of substrates, CCNF-20@MOF showed a specific capacity of 361.50 C g-1 at 0.5 A g-1, whose charge storage mechanism is dominated by diffusion control. Meanwhile, a bamboo-derived carbon material (BBC) was designed in the solid-state asymmetric supercapacitor (CCNF-20@MOF//BBC). The device exhibited an energy density of 38.89 Wh kg-1 at the power density of 800.02 W kg-1 and excellent cycling stability, that exceed many MOFs based devices. Moreover, it could be successfully used for LED light-emitting, demonstrating a good application prospect. This work provides a feasible strategy for the improved performance of MOFs and CNFs based materials in the field of energy storage.

The loss of hepatitis B virus receptor NTCP/SLC10A1 in human liver cancer cells is due to epigenetic silencing.

Human Na+-taurocholate cotransporting polypeptide (hNTCP) is predominantly expressed in hepatocytes, maintaining bile salt homeostasis and serving as a receptor for hepatitis B virus (HBV). hNTCP expression is downregulated during hepatocellular carcinoma (HCC) development. In this study, we investigated the molecular mechanisms underlying hNTCP dysregulation using HCC tissues and cell lines, and primary human hepatocytes (PHHs). Firstly, we observed a significant reduction of hNTCP in HCC tumors compared to adjacent and normal tissues. Additionally, hNTCP mRNA levels were markedly lower in HepG2 cells compared to PHHs, which was corroborated at the protein level by immunoblotting. Sanger sequencing confirmed identical sequences for hNTCP promoter, exons, and mRNA coding sequences between PHH and HepG2 cells, indicating no mutations or splicing alterations. We then assessed the epigenetic status of hNTCP. The hNTCP promoter, with low CG content, showed no significant methylation differences between PHH and HepG2 cells. Chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR) revealed a loss of activating histone posttranslational modification (PTM) H3K27ac near the hNTCP transcription start site (TSS) in HepG2 cells. This loss was also confirmed in HCC tumor cells compared to adjacent and background cells. Treating HepG2 cells with histone deacetylase inhibitors enhanced H3K27ac accumulation and glucocorticoid receptor (GR) binding at the hNTCP TSS, significantly increasing hNTCP mRNA and protein levels, and rendering the cells susceptible to HBV infection. In summary, histone PTM-related epigenetic mechanisms play a critical role in hNTCP dysregulation in liver cancer cells, providing insights into hepatocarcinogenesis and its impact on chronic HBV infection. IMPORTANCE: HBV is a hepatotropic virus that infects human hepatocytes expressing the viral receptor hNTCP. Without effective antiviral therapy, chronic HBV infection poses a high risk of liver cancer. However, most liver cancer cell lines, including HepG2 and Huh7, do not support HBV infection due to the absence of hNTCP expression, and the mechanism underlying this defect remains unclear. This study demonstrates a significant reduction of hNTCP in hepatocellular carcinoma samples and HepG2 cells compared to normal liver tissues and primary human hepatocytes. Despite identical hNTCP genetic sequences, epigenetic analyses revealed a loss of the activating histone modification H3K27ac near the hNTCP transcription start site in cancer cells. Treatment with histone deacetylase inhibitors restored H3K27ac levels, reactivated hNTCP expression, and rendered HepG2 cells susceptible to HBV infection. These findings highlight the role of epigenetic modulation in hNTCP dysregulation, offering insights into hepatocarcinogenesis and its implications for chronic HBV infection.

Gelatin-coated glutathione depletion and oxygen generators in potentiated chemotherapy for pancreatic cancer.

Chemotherapy is generally acknowledged as an effective method for pancreatic cancer (PC). However, its treatment efficacy is often compromised due to inefficient drug delivery and drug resistance propensity of tumor tissues. The purpose of this study is to design and develop a novel drug delivery system (Manganese-doped mesoporous silica nanoparticles, Mn-MSN) in which paclitaxel (PTX), a conventional chemotherapeutic agent used to effectively treat pancreatic cancer clinically. Through cross-linking with glutaraldehyde, gelatin (Ge) was encapsulated on the carrier surface, endowing the nanoparticles (Ge-Mn-MSN@PTX) with excellent biocompatibility, low hemolytic activity, and enzyme-responsive degradation. Mn was added for the following purposes: (1) catalyzing hydrogen peroxide (H2O2) to generate oxygen (O2), thereby alleviating tumor hypoxia and drug resistance; (2) depleting glutathione (GSH), inducing intracellular lipid peroxidation and ferroptosis; (3) enabling real-time monitoring of the therapeutic efficacy of the nanoparticles via magnetic resonance imaging (MRI). The experimental results demonstrated that Ge-Mn-MSN@PTX has satisfactory biosafety, antitumor activity, controlled drug release as well as imaging tracking capabilities. In the SW1990 nude mice model, the Ge-Mn-MSN@PTX effectively inhibited tumor growth by suppressing the expression of the resistance protein P-glycoprotein (P-gp) and inducing ferroptosis. In conclusion, the designed gelatin-coated Mn-MSN shows potential for application in future pancreatic cancer therapy.

NEDD4 family ubiquitin ligase AIP4 interacts with Alix to enable HBV naked capsid egress in an Alix ubiquitination-independent manner.

Hepatitis B virus (HBV) exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for virion budding. In addition to enveloped virions, HBV-replicating cells nonlytically release non-enveloped (naked) capsids independent of the integral ESCRT machinery, but the exact secretory mechanism remains elusive. Here, we provide more detailed information about the existence and characteristics of naked capsid, as well as the viral and host regulations of naked capsid egress. HBV capsid/core protein has two highly conserved Lysine residues (K7/K96) that potentially undergo various types of posttranslational modifications for subsequent biological events. Mutagenesis study revealed that the K96 residue is critical for naked capsid egress, and the intracellular egress-competent capsids are associated with ubiquitinated host proteins. Consistent with a previous report, the ESCRT-III-binding protein Alix and its Bro1 domain are required for naked capsid secretion through binding to intracellular capsid, and we further found that the ubiquitinated Alix binds to wild type capsid but not K96R mutant. Moreover, screening of NEDD4 E3 ubiquitin ligase family members revealed that AIP4 stimulates the release of naked capsid, which relies on AIP4 protein integrity and E3 ligase activity. We further demonstrated that AIP4 interacts with Alix and promotes its ubiquitination, and AIP4 is essential for Alix-mediated naked capsid secretion. However, the Bro1 domain of Alix is non-ubiquitinated, indicating that Alix ubiquitination is not absolutely required for AIP4-induced naked capsid secretion. Taken together, our study sheds new light on the mechanism of HBV naked capsid egress in viral life cycle.

SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML.

The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether-and if so, how-SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.

Hyperactivation of p53 contributes to mitotic catastrophe in podocytes through regulation of the Wee1/CDK1/cyclin B1 axis.

Podocyte loss in glomeruli is a fundamental event in the pathogenesis of chronic kidney diseases. Currently, mitotic catastrophe (MC) has emerged as the main cause of podocyte loss. However, the regulation of MC in podocytes has yet to be elucidated. The current work aimed to study the role and mechanism of p53 in regulating the MC of podocytes using adriamycin (ADR)-induced nephropathy. In vitro podocyte stimulation with ADR triggered the occurrence of MC, which was accompanied by hyperactivation of p53 and cyclin-dependent kinase (CDK1)/cyclin B1. The inhibition of p53 reversed ADR-evoked MC in podocytes and protected against podocyte injury and loss. Further investigation showed that p53 mediated the activation of CDK1/cyclin B1 by regulating the expression of Wee1. Restraining Wee1 abolished the regulatory effect of p53 inhibition on CDK1/cyclin B1 and rebooted MC in ADR-stimulated podocytes via p53 inhibition. In a mouse model of ADR nephropathy, the inhibition of p53 ameliorated proteinuria and podocyte injury. Moreover, the inhibition of p53 blocked the progression of MC in podocytes in ADR nephropathy mice through the regulation of the Wee1/CDK1/cyclin B1 axis. Our findings confirm that p53 contributes to MC in podocytes through regulation of the Wee1/CDK1/Cyclin B1 axis, which may represent a novel mechanism underlying podocyte injury and loss during the progression of chronic kidney disorder.

Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription.

Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65's antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins' capacity to inhibit HBV transcription and highlight TRIM65's pivotal role in this process.

Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.

Optimizing the efficiency of definitive endoderm (DE) differentiation is necessary for the generation of diverse organ-like structures. In this study, we used the small molecule inhibitor saracatinib (SAR) to enhance DE differentiation of human embryonic stem cells and induced pluripotent stem cells. SAR significantly improved DE differentiation efficiency at low concentrations. The interaction between SAR and Focal Adhesion Kinase (FAK) was explored through RNA-seq and molecular docking simulations, which further supported the inhibition of DE differentiation by p-FAK overexpression in SAR-treated cells. In addition, we found that SAR inhibited the nuclear translocation of Yes-associated protein (YAP), a downstream effector of FAK, which promoted DE differentiation. Moreover, the addition of SAR enabled a significant reduction in activin A (AA) from 50 to 10 ng/mL without compromising DE differentiation efficiency. For induction of the pancreatic lineage, 10 ng/ml AA combined with SAR at the DE differentiation stage yielded a comparative number of PDX1+/NKX6.1+ pancreatic progenitor cells to those obtained by 50 ng/ml AA treatment. Our study highlights SAR as a potential modulator that facilitates the cost-effective generation of DE cells and provides insight into the orchestration of cell fate determination.

Infectious bronchitis virus (IBV) triggers autophagy to enhance viral replication by activating the VPS34 complex.

Autophagy plays an important role in the lifecycle of viruses. However, there is currently a lack of systematic research on the relationship between Infectious Bronchitis Virus (IBV) and autophagy. This study aims to investigate the impact of IBV on autophagy and the role of autophagy in viral replication. We observed that IBV infection increased the expression of microtubule-associated protein 1 light chain 3, a marker of autophagy, decreased the expression of sequestosome 1, and led to elevated intracellular LC3 puncta levels. These findings suggest that IBV infection activates the autophagic process in cells. To investigate the impact of autophagy on the replication of IBV, we utilized rapamycin as an autophagy activator and 3-methyladenine as an autophagy inhibitor. Our results indicate that IBV promotes viral replication by inducing autophagy. Further investigation revealed that IBV induces autophagosome formation by inhibiting the mTOR-ULK1 pathway and activating the activity of vacuolar protein sorting 34 (VPS34), autophagy-related gene 14, and the Beclin-1 complex. VPS34 plays a crucial role in this process, as inhibiting VPS34 protein activity enhances cell proliferation after IBV infection. Additionally, inhibiting VPS34 significantly improves the survival rate of IBV-infected chicks, suppresses IBV replication in the kidney, and alleviates tracheal, lung, and kidney damage caused by IBV infection. In summary, IBV infection can induce autophagy by modulating the mTOR/ULK1 signaling pathway and activating the VPS34 complex, while autophagy serves to promote virus replication.

Fe3O4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer.

This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4for T2imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles throughin vitroandin vivocell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2relaxation rate 42.29 mM-1s-1, magnetic saturation strength of 27.58 emg g-1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated byin vitroandin vivostudies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and goodin vivobiocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.

Bimetallic Organic Gel for Effective Methyl Orange Dye Adsorption.

A bimetallic organic gel (MOG-Fe/Al) was synthesized through the solvothermal method. The gel state of the product obtained under optimized gel formation conditions is sufficient to carry 2 g of weight for a long time. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) technique, and X-ray photoelectron spectroscopy (XPS) analysis confirmed the structures and morphologies of the synthesized materials. MOG-Fe/Al, with good stability, excellent durability, and wide applicability, exhibited efficient MO adsorption capacity as high as 335.88 mg/g at 25 °C. Adsorption-influencing factors including solution pH, contact time, and temperature were investigated. The adsorption performance of the bimetallic organic gel was better than that of the monometallic organic gels (MOG-Fe and MOG-Al), and its adsorption processes were in accordance with the pseudo-second-order kinetic and Langmuir isothermal models. The excellent adsorption capacity of the MOG-Fe/Al is due to its surface structure, pore volume, π-π interactions, hydrogen bonds, and electrostatic interactions.

A highly sensitive optical fiber sensor enables rapid triglycerides-specific detection and measurement at different temperatures using convolutional neural networks.

For specific recognition and sensitive detection of triglycerides (TGs), an optical fiber sensor (OFS) based on an enhanced core diameter mismatch was proposed. The sensitivity of the sensor is significantly increased due to the repetitive excitation of the higher-order cladding modes. A technique for immobilizing lipase using covalent binding technology was presented and demonstrated by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy. The interference dip of the sensor was shifted due to TGs being hydrolyzed in the presence of lipase. The sensor shows an optimal response within 3 min and exhibits a high sensitivity of 0.9933 nm/(mg/ml) and a limit of detection of 0.0822 mg/ml in the concentration range 0-8 mg/ml at a temperature of 37 °C and a pH of 7.4. The response of the sensor to TGs concentration at different temperatures and pH was investigated. The reproducibility, reusability, and stability of the proposed sensor were tested and verified experimentally. The biosensor is highly specific for TGs and unaffected by many other interfering substances. Further, the measurement of TGs concentration at different temperatures was realized. This method provides a new way to detect TGs rapidly and reliably and has potential applications in medical research and clinical diagnosis.

Comparative Study on Interfacial Properties, Foam Stability, and Firefighting Performance of C6 Fluorocarbon Surfactants with Different Hydrophilic Groups.

Liquid fuel is flammable and hazardous, and a pool fire is one of the most serious disasters. Therefore, it is important to develop high-performance firefighting agents. To synthesize aqueous film-forming foam (AFFF) formulations, two C6 short-chain fluorocarbon surfactants Capstone 1157 (FC1157) and sodium perfluorohexylethyl sulfonate (SF852) with different hydrophilic groups were introduced, and three hydrocarbon surfactants sodium dodecyl sulfate (SDS), decyl glucoside (APG0810), and coco glucoside (APG0814) were chosen. The AFFF formulations based on the short-chain fluorocarbon-hydrocarbon compounding system were developed, and the firefighting performance of the formulations was assessed according to the standard pool fire extinction test. The results indicated that amphoteric FC1157 was slightly more effective than anionic SF852 in extinguishing small-scale pool fires and could reduce heat flux more effectively than SF852. Fluorocarbon surfactant FC1157 has been shown to suppress large pool fires much better than SF852, possibly due to its higher foam stability, higher foaming property, lower dynamic surface tension, and lower bubble coarsening rate. Both formulations we studied were more effective than commercial AFFF formulations. A concentration of 0.1-0.3% of FC1157 in an AFFF solution was optimal for extinguishing high-boiling-point oil fires.

Advanced Etching Techniques of LiNbO3 Nanodevices.

Single LiNbO3 (LNO) crystals are widely utilized in surface acoustic wave devices, optoelectronic devices, and novel ferroelectric memory devices due to their remarkable electro-optic and piezoelectric properties, and high saturation and remnant polarizations. However, challenges remain regarding their nanofabrication that hinder their applications. The prevailing etching techniques for LNO encompass dry etching, wet etching, and focused-ion-beam etching, each having distinct merits and demerits. Achieving higher etching rates and improved sidewall angles presents a challenge in LNO nanofabrication. Building upon the current etching researches, this study explores various etching methods using instruments capable of generating diverse plasma densities, such as dry etching in reactive ion etching (RIE) and inductively coupled plasma (ICP), proton exchange-enhanced etching, and wet chemical etching following high-temperature reduction treatment, as well as hybrid dry and wet etching. Ultimately, after employing RIE dry etching combined with wet etching, following a high-temperature reduction treatment, an etching rate of 10 nm/min and pretty 90° sidewall angles were achieved. Furthermore, high etching rates of 79 nm/min with steep sidewall angles of 83° were obtained using ICP dry etching. Additionally, using SiO2 masks, a high etching rate of 108 nm/min and an etching selectivity ratio of 0.86:1 were achieved. Distinct etching conditions yielded diverse yet exceptional results, providing multiple processing paths of etching for the versatile application of LNO.

Conditional replication and secretion of hepatitis B virus genome uncover the truncated 3' terminus of encapsidated viral pregenomic RNA.

IMPORTANCE: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.

Metabolic diversity of tumor-infiltrating T cells as target for anti-immune therapeutics.

Tumor-infiltrating T cells are promising drug targets to modulate the tumor microenvironment. However, tumor-infiltrating T lymphocytes, as central targets of cancer immunotherapy, show considerable heterogeneity and dynamics across tumor microenvironments and cancer types that may fundamentally influence cancer growth, metastasis, relapse, and response to clinical drugs. The T cell heterogeneity not only refers to the composition of subpopulations but also divergent metabolic states of T cells. Comparing to the diversity of tumor-infiltrating T cell compositions that have been well recognized, the metabolic diversity of T cells deserves more attention for precision immunotherapy. Single-cell sequencing technology enables panoramic stitching of the tumor bulk, partly by showing the metabolic-related gene expression profiles of tumor-infiltrating T cells at a single-cell resolution. Therefore, we here discuss T cell metabolism reprogramming triggered by tumor microenvironment as well as the potential application of metabolic targeting drugs. The tumor-infiltrating T cells metabolic pathway addictions among different cancer types are also addressed in this brief review.

A novel antibody-KSP inhibitor conjugate improves KSP inhibitor efficacy in vitro and in vivo.

Many clinical trials of kinesin spindle protein (KSP) inhibitors have failed due to issues such as high toxicity and a short circulation half-life in vivo. To address the limitations of current KSP inhibitors and thus broad its use in antitumor therapy, this study applied antibody-drug conjugate (ADC) technology to the KSP inhibitor SB-743921, which was coupled with the HER2-specific antibody trastuzumab using a cathepsin B-dependent valine-alanine (Val-Ala, VA) dipeptide-type linker to generate H2-921. Ex vivo and in vivo analyses of H2-921 showed an increased half-life of SB-743921 and prolonged contact time with tumor cells. Furthermore, H2-921 induced apoptosis and incomplete autophagy in HER2-positive cells. In the in vivo analyses, H2-921 had significant tumor-targeting properties, and tumor inhibition by H2-921 was greater than that by traditional KSP inhibitors but similar to that by the positive control drug T-DM1. In conclusion, this study describes a novel application of ADC technology that enhances the antitumor effects of a KSP inhibitor and thus may effectively address the poor clinical efficacy of KSP inhibitors.