Hypoimmune CD19 CAR T cells evade allorejection in patients with cancer and autoimmune disease.

Off-the-shelf CAR T cells need to reliably escape allogeneic immune responses to become universal medicines. The primary T cell product SC291 was engineered with a CD19 CAR, T cell receptor alpha constant (TRAC) knockout, and the hypoimmune (HIP) edits of HLA depletion and CD47 overexpression. Here, we report exploratory immune analyses from the ARDENT (NCT05878184) and GLEAM (NCT06294236) trials with HIP-edited CD19 CAR T cells.

Screening of Theaflavins That Inhibit Proliferation of Nasopharyngeal Carcinoma Cells Through Metabolomics Approaches.

To study the inhibitory mechanism of theaflavins on nasopharyngeal carcinoma cells to define a solid Chinese herbal antitumor remedy through metabolomics approaches. Various concentrations of theaflavin-3,3'-digallate (TF3) were examined for their effects on proliferation, migration, invasion, and apoptosis of nasopharyngeal carcinoma (NPC) cells by CCK-8, colony-forming assay, wound healing assay, trans-well migration assay, and Hoechst staining assay. Moreover, metabolomics analysis along with UHPLC-Q-TOF mass spectrometry and UHPLC-Q-Exactive Orbitrap mass spectroscopic analyses were also performed.

Hypoimmune FK binding protein 12-knockout CD19 CAR T cells achieve deep tissue B-cell depletion and control Nalm6 tumors in immunosuppressed humanized mice.

Autologous chimeric antigen receptor (CAR) T-cell therapy in solid-organ transplant recipients on life-long systemic immunosuppression has so far been disappointing. The mTOR inhibitors tacrolimus (Tac) and rapamycin (Rapa) are among the most common immunosuppressive drugs. While they prevent organ allograft rejection, they also suppress the efficacy and persistence of the CAR T-cell product.

Hypoimmune CD19 CAR T cells treat allogeneic mice with features of spontaneous systemic lupus erythematosus.

Hypoimmune (HIP) MHC class I- and II-deficient and CD47-overexpressing CD19 CAR T cells were generated and tested in an allogeneic NZB/W mouse model of spontaneous systemic lupus erythematosus with established disease. HIP CAR T cells showed persistent engraftment, achieved lasting deep tissue B cell depletion, diminished antibody levels and systemic pro-inflammatory cytokine levels, mitigated proteinuria and glucosuria, alleviated structural kidney injury, and improved survival after 21 weeks. HIP CAR T cells did not induce any immune activation in this fully allogeneic model and thus completely escaped allorejection.

Protective effect of Salvianolic acid B against atherosclerosis: a preclinical systematic review and meta-analysis.

Background: Atherosclerosis is the most common cause of cardiovascular disease, with high morbidity and mortality rates globally. Salvianolic acid B (Sal B), the most active and abundant component of the water-soluble extract of the traditional Chinese medicine Danshen, has been demonstrated to exert atheroprotective effects; nonetheless, its protective potential remains unclear. This study aimed to evaluate the preclinical efficacy of Sal B in the treatment of atherosclerosis and summarize the relevant mechanisms of action to provide evidence for its use in the treatment of atherosclerosis.

ITGA4 Contributes to 5-Fluorouracil Resistance by Up-Regulating PI3K/AKT Signaling: Evidence from Network Pharmacology, Molecular Docking and Experimental Verification.

Objective: 5-Fluorouracil (5-FU) is a mainstream drug used in chemotherapy and chemoradiotherapy regimens for the clinical treatment of malignancies, such as gastric cancer (GC), colorectal cancer, and breast cancer. However, the molecular mechanism of action of 5-FU in GC has not yet been studied using a network pharmacology approach.

Methods: The mechanism of action of 5-FU in GC was determined using a network pharmacology technique, and our findings were confirmed by various computational approaches and experimental tests using the GeneCards database, ChEMBL database, STRING database, molecular docking, molecular dynamics simulation, DAVID, GEPIA, Kaplan‒Meier Plotter, CCK-8 assays, colony formation experiments, cell proliferative assay, apoptosis assays, wound-healing assays, Real-time PCR and Western blot tests.

Inhibition of polymorphonuclear cells averts cytotoxicity against hypoimmune cells in xenotransplantation.

Allogeneic, immune-evasive hypoimmune (HIP) cell therapeutics that are HLA-depleted and overexpress CD47 create the opportunity to treat immunocompetent patients with cancer, degenerative, or autoimmune diseases. However, HIP cell therapy has not yet been established for xenotransplantation. Here we engineer, for human-to-non-human primate studies, human HIP* endothelial cells (EC) that are HLA-depleted and express macaque CD47 to allow compatibility with the macaque SIRPα immune checkpoint.

Highly Efficient Yolk-Shell Photocatalyst Constructed by Integration of NiP and CuO Nanoparticles to Defective Metal-Organic Frameworks for Visible-Light-Driven Amine Oxidation.

Realizing the directional migration of photogenerated carriers plays an important role in improving the photocatalytic performance. Meanwhile, light-driven oxidative coupling of benzylamine under ambient conditions with an inexpensive catalyst is highly desirable for the industrial field. Herein, via in situ synthesis, defect engineering, and photodeposition, a yolk-shell nanostructured photocatalyst, NiP@OH-NH-UiO-66@CuO, featuring nickel phosphide (NiP) nanoparticles (NPs) trapped inside a defect engineered metal-organic framework (MOF, namely OH-NH-UiO-66) and CuO NPs adhering on the surface of MOFs, has been rationally fabricated for the achievement of spatial separation of oxidation/reduction cocatalyst in photocatalytic reaction systems.

[Reflections and suggestions on the researches of acupuncture-moxibustion for idiopathic facial palsy].

This article analyzes the current status of the researches on acupuncture-moxibustion for idiopathic facial palsy (Bell's palsy). Acupuncture-moxibustion is widely applied in treatment of Bell's palsy and the relevant researches are enriched. But the hierarchical discussion on the effectiveness is reported inadequately.

Neurotoxic Effects of Atrazine on Dopaminergic System via miRNAs and Energy-Sensing Pathways.

Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a globally prevalent herbicide known to induce dopaminergic neurotoxicity at high concentrations. MicroRNAs (miRNAs), pivotal in regulating gene expression post-transcriptionally, play essential roles in neuronal differentiation, proliferation, and apoptosis. This study investigates the effects of ATR on the dopaminergic system and behavioral responses in rats, with a particular focus on critical dopaminergic proteins such as tyrosine hydroxylase (TH), nuclear receptor related-1 protein (NURR1), and α-synuclein.

The neural basis of dialectical thinking: recent advances and future prospects.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored.

An integrated framework of life-cycle environmental, human health, and economic impact assessment for urban water systems.

Water scarcity presents a pressing and lasting challenge to many large cities, necessitating adaptations in urban water systems. Developing reliable water resources is crucial for enhancing water security, yet concerns regarding costs and environmental impacts persist. To address this, we have developed an integrated framework that combines life cycle assessment (LCA), quantitative microbial risk assessment (QMRA), and life cycle costing (LCC) for evaluating the environmental, public health, and economic impacts of water systems.

A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment.

Background: The Homeobox (HOX) gene family are conserved transcription factors that are essential for embryonic development, oncogenesis, and cancer suppression in biological beings. Abnormally expressed HOX genes in cancers are directly associated with prognosis.

Methods: Public databases such as TCGA and the R language were used to perform pan-cancer analyses of the HOX family in terms of expression, prognosis, and immune microenvironment.

The EZH2/MCM Complex/hTERT axis facilitates hepatocellular carcinoma progression by inhibiting cellular senescence.

The complex pathogenesis of hepatocellular carcinoma (HCC) limits the effectiveness of current therapies. Through RNA sequencing of cancerous and adjacent non-cancerous tissues from six HCC patients, we identified a significant upregulation of MCM2-7 genes, which encode proteins that form the MCM complex, a DNA helicase involved in DNA replication and cell cycle progression. We focused on MCM2, MCM3, and MCM7, and observed that knockdown of these proteins inhibited HCC cell proliferation.

[Discussion on the commonalities of scalp acupuncture schools and the feasibility of a unified scalp acupuncture protocol].

The data of 44 scalp acupuncture schools are collected to analyze their commonalities in theoretical foundations, needling sites, techniques, and indications. The integration of these characteristics into an optimized, unified scalp acupuncture protocol has become an inevitable trend. The paper discusses the potential for a unified scalp acupuncture protocol from aspects such as theoretical unification, the relationships between point areas, lines, and sites, and needle numbers.

The HIP mouse and all of its organs are completely invisible to allogeneic immune cells.

Hypoimmune (HIP) allogeneic cell therapeutics hold the promise to allow off-the-shelf treatments for a broad patient population. Our HIP approach includes the depletion of major histocompatibility complex (MHC) class I and II molecules and the overexpression of Cd47. Here, we report the engineering of HIP mice that stably exhibit the HIP phenotype in all cell types.

The RNA-binding protein CMSS1 promotes the progression of non-small cell lung cancer by regulating the telomerase protein subunit hTERT.

Aims: High telomerase activity has been detected in over 85 % of tumors, with the activation of hTERT being the most crucial mechanism for re-establishing telomerase activity. Activation of hTERT maintains telomere length in cells, enabling cancer cells to proliferate indefinitely. Nevertheless, the specific mechanism of telomerase activation in non-small cell lung cancer (NSCLC) remains unclear, and post-transcriptional regulation of hTERT could be a potential activation mechanism.

Exploring factors influencing the quality of life in diabetes: a network analysis-based study.

Objective: The purpose of this study was to explore the key pathways leading to low quality of life in type 2 diabetes patients by means of network analysis, so as to provide the possibility of effective interventions.

Methods: The study involved 1,011 adult type 2 diabetes patients from a tertiary hospital in Harbin. Data was collected through questionnaires, and network analysis was performed using R software to assess the centrality and predictability of each node.

The chain mediation effects of self-confidence and positive coping style on academic satisfaction and professional identity among Chinese medical students.

Due to the importance of medical students in the buildup of the health system and the influence of professional identity in their study, the aim of the study is to focus on the impact of academic satisfaction and professional identity on Chinese medical students during their career transformation, taking into consideration other factors that play a role in this relationship. 735 junior and senior medical university students from two training hospital were surveyed by using a cluster sampling method. The questionnaire included academic satisfaction scale, career transition psychological scale, simple coping style questionnaire and professional identity questionnaire.

Pyrroloquinoline Quinone (PQQ): Its impact on human health and potential benefits: PQQ: Human health impacts and benefits.

Pyrroloquinoline Quinone (PQQ) is a redox-active quinone molecule with significant implications for human health. Originally identified as a bacterial cofactor, PQQ has since been lauded for its diverse biological and therapeutic activities. It serves as an essential cofactor for oxidative enzymes that are vital for mitochondrial function and ATP synthesis.

Longitudinal correlates of learning burnout among Chinese adolescents during the COVID-19 pandemic: A cross-lagged panel network analysis.

Background: Learning burnout as a serious psychological distress problem among adolescents during the COVID-19 pandemic was investigated using the cross-lagged panel network models.

Methods: A three-wave study using a sample of 11 to 18-year-olds in China was conducted, with baseline data collected in June 2020 (n = 4156) and follow-ups in December 2020 (n = 3209) and August 2021 (n = 2324). Two temporal cross-lagged panel network models were computed to analyze adolescent learning burnout over time.

A truncated B-box zinc finger transcription factor confers drought sensitivity in modern cultivated tomatoes.

Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18) that encodes a C-terminal truncated protein.

The tomato WRKY-B transcription factor modulates lateral branching by targeting , , and .

Lateral branching is a crucial agronomic trait that impacts crop yield. In tomato ( ), excessive lateral branching is unfavorable and results in substantial labor and management costs. Therefore, optimizing lateral branching is a primary objective in tomato breeding.

Delivery approaches of immunomodulatory nucleic acids for cancer therapy.

Messenger RNA (mRNA) vaccines have made remarkable public health contributions during the pandemic and initiated a new era for nucleic acid-based therapeutics. With the unique strength of nucleic acids, including not only mRNA but also DNA, microRNA, small interfering RNA (siRNA), and other nucleic acids, either in tuning off genes or introducing function, nucleic acid therapeutics have been regarded as potential candidates for the treatment of many different diseases, especially for the immunomodulation in cancer. However, the scope of the applications was limited by the challenges in delivery due to intrinsic properties of nucleic acids including low stability, immunogenicity, and toxicity.