OBJECTIVE:To determine whether robotic pancreatoduodenectomy (RPD) is non-inferior to open pancreatoduodenectomy (OPD) in terms of postoperative functional recovery, without compromising safety or oncological quality. DESIGN:Multicentre, single masked, phase 3, non-inferiority randomised controlled trial. SETTING:Seven tertiary high volume pancreatic centres in China, 15 June 2020 to 28 November 2024. PARTICIPANTS:268 adults with resectable pancreatic or periampullary disease. INTERVENTIONS:Participants were randomised to receive standardised RPD (n=142) or OPD (n=126), with enhanced recovery pathways. MAIN OUTCOME MEASURES:The primary outcome was time from surgery to postoperative functional recovery, defined as adequate pain control without parenteral analgesia, ≥50% oral intake without intravenous fluids, independent mobilisation, and absence of active intra-abdominal infection. The restricted mean event time (RMET) within 40 days was a summary for time from surgery to postoperative functional recovery. Secondary outcomes included operative metrics, disease related outcomes, length of stay, postoperative morbidity, including complications of Clavien-Dindo grade II or higher (defined as complications requiring drug treatment or more intensive intervention), and hospital admission costs. RESULTS:Overall, 254 of 268 randomly assigned participants (mean age 62 years; 172 (64.2%) men) underwent surgery, completed follow-up, and were included in the modified intention-to-treat population; 14 did not undergo surgery. In the modified intention-to-treat population, the RMET was 12.1 days (95% confidence interval (CI) 11.2 to 13.1) in the RPD group and 16.0 days (14.5 to 17.5) in the OPD group (difference -3.9 days, 95% CI -5.6 to -2.2; P<0.001). Operative time was longer in the RPD group (300 minutes (interquartile range (IQR) 240-360 minutes) versus 270 (210-300) minutes in the OPD group, P<0.001) but postoperative length of stay was shorter in the RPD group (13 (IQR 11-16) days v 16 (13-20) days, P<0.001). Overall postoperative morbidity was 31.1% (41/132) in the RPD group versus 36.1% (44/122) in the OPD group and incidence of any complications of Clavien-Dindo grade II or higher was 23.5% (31/132) versus 34.4% (42/122), respectively. 90 day mortality was 0.8% (1) in the RPD group and 2.5% (3) in the OPD group. Median total costs of hospital admission (including readmission cost) were higher in the RPD group than in the OPD group (¥130 905 (£14 369; $19 351; €16 628) (IQR ¥114 853-¥152 547) v ¥108 071 (¥92 134-¥128 035), difference ¥22 834 (95% CI ¥16 744 to ¥30 522); P<0.001). CONCLUSIONS:In high volume centres with credentialled surgeons, RPD met the non-inferiority margin for time from surgery to postoperative functional recovery, with comparable disease related outcomes and overall burden from postoperative complications. To generate wider system level efficiency gains, the implementation of RPD should take account of institutional expertise, procedural volume, acquisition of robotic surgical platforms and maintenance costs, and the potential for shorter hospital stay. TRIAL REGISTRATION:ClinicalTrials.gov NCT04400357.

Abstract Immunotherapy has limited efficacy in acute myeloid leukemia (AML), partly because innate immune cells such as macrophages remain inactive. Nucleotide metabolism regulates key cellular processes, and cytidine triphosphate synthase 1 (CTPS1), the enzyme responsible for de novo CTP synthesis, is essential for cell proliferation. We previously showed (Liu, 2024 ASH) that high CTPS1 activity promotes AML growth and suppresses antitumor immunity. Accordingly, the CTPS1 inhibitor STP-B significantly prolonged the survival of immunocompetent leukemic mice in an immune-dependent manner. Across TCGA cancers, CTPS1 expression negatively correlated with M1-macrophage signatures.Here, we show that STP-B exerts anti-AML activity by (1) inducing myeloid differentiation, especially M1-like macrophage polarization through dNTP imbalance, and (2) activating IFN-I signaling by blocking CTPS1-mediated deamidation of IRF3 and histone H1. In a syngeneic MLL-AF9 (MA9) model, daily oral STP-B (100 mg/kg, 3 weeks) reduced leukemia burden and markedly increased CD11b+F4/80+ macrophages, enriching the M1-like subset. Macrophage depletion completely abolished the survival benefit. Combination with anti-CD47 produced strong synergy. Transcriptomic analysis of MA9 cells and non-malignant myeloid cells showed induction of M1-associated genes (Il6, Il1a, Cxcl9, Cxcl10). Ex vivo, STP-B-treated BMDMs displayed significantly enhanced phagocytosis of MA9 cells. To evaluate human hematopoietic effects, CD34+ cord blood-engrafted NSG mice were treated with STP-B. While total human CD45+ levels were unchanged, myeloid (CD33+CD11b+), monocyte (CD14+CD64+), and HLA-DR+CD86+ M1-like macrophage populations increased, with higher expression of myeloid transcription factors and human M1 genes. Metabolomic profiling of THP-1 cells confirmed that STP-B markedly reduced intracellular CTP, indicating nucleotide imbalance. Ribonucleotide reductase inhibition partially restored balance, reversed differentiation, and suppressed STP-B-induced M1-gene expression, supporting a nucleotide-driven differentiation mechanism. GSEA demonstrated induction of IFN-I-responsive genes. STP-B increased γH2AX and nuclear S9.6 staining, consistent with DNA damage caused by inhibition of CTPS1-mediated histone H1 deamidation. STP-B also blocked CTPS1-dependent IRF3 deamidation, enhancing ISG expression. Reconstitution of CTPS1-knockout THP-1 cells with a glutaminase-deficient CTPS1 mutant similarly increased ISGs, indicating that CTPS1 deamidation activity suppresses IFN signaling. Together, these findings show that STP-B promotes macrophage specification and innate immune activation, defining STP-B as a leukemia-ablating agent with strong immunostimulatory properties. Citation Format: Meng Liu, Lei Zhang, Xin He, Haojie Dong, Yang Li, Shuaishuai Ge, Guohua Wu, Yadav P. Umesh, Wei Chen, Pinghui Feng, Guido Marcucci, Ling Li. Pharmacological targeting of CTPS1 elicits macrophage-mediated anti-leukemia immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2572.

ABSTRACT:Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is required for cancer cell proliferation, but whether PRMTs mediate resistance to therapy remains unclear. Here, we performed loss-of-function screens in venetoclax-resistant (VEN-R) acute myeloid leukemia (AML) patient-derived xenograft cells and found that PRMT9 plays a critical role in promoting VEN resistance. Specifically, VEN-R AML samples exhibited high levels of PRMT9, and PRMT9 inhibition resensitized AML cells to VEN treatment. In preclinical resistant models, genetic ablation of PRMT9 synergized with VEN to eradicate AML cells. Consistently, pharmacologic inhibition of PRMT9 combined with VEN produced similar effects in VEN-R AML mouse models. Mechanistically, PRMT9 ablation disrupted RNA splicing by inducing exon skipping in mRNA encoding ALG13, an uridine diphosphate (UDP)-N-acetylglucosaminyltransferase subunit, thereby downregulating expression of the VEN efflux transporter encoded by the adenosine triphosphate-binding cassette subfamily C member 1 gene. PRMT9 inhibition also suppressed protein synthesis, leading to downregulation of short-lived oncoproteins such as MCL1. These findings establish a connection between PRMT9-mediated arginine methylation and poor VEN responsiveness and demonstrate that targeting PRMT9 may represent a viable strategy to overcome VEN resistance.

Immunotherapy, including immune checkpoint inhibitors, antagonizes many hematologic malignancies, but has transient effects on acute myeloid leukemia (AML), as innate immune cells like macrophages remain inactive. Nucleotide metabolism is critical to regulate multiple cellular functions, and cytidine triphosphate synthase 1 (CTPS1), which catalyzes de novo CTP biosynthesis, is essential for cell proliferation. We previously (Liu, 2024, ASH) showed that high CTPS1 activity promotes cancer cell growth and suppresses anti-AML immunity. Accordingly, the administration of the CTPS1 inhibitor STP-B significantly extended the survival of immunocompetent leukemic mice, an effect requiring an immune response. Analysis of TCGA cohorts, including AML, glioblastoma, and non-small cell lung cancer, consistently demonstrated a negative correlation between CTPS1 expression and macrophage M1 signature. Herein, we show that targeting CTPS1 by STP-B exerts potent anti-AML activity by 1) promoting myeloid differentiation, in particular, macrophage M1 polarization triggered by dNTP imbalance, and 2) stimulating IFN-I signaling by inhibiting CTPS1-mediated deamidation of IRF3 and histone H1. To further define these mechanisms, we first employed a syngeneic MLL-AF9 (MA9) leukemia transplant model. Leukemic mice were administered STP-B orally (100 mg/kg/i.g./day) for 3 weeks. Then, full-spectrum flow cytometry revealed that treatment decreased leukemia burden and markedly increased CD11b⁺F4/80⁺ macrophage number and the frequency of the M1-like subset. Macrophage depletion by liposomal clodronate before STP-B treatment completely abolished survival advantages seen in STP-B-treated mice. Moreover, in the MA9 mouse model, treatment with STP-B and anti-CD47 in vivo synergized to antagonize AML, highlighting the significance of macrophage function. Transcriptomic profiling of MA9 cells (GFP+) and non-malignant myeloid cells (GFP-CD11b+) showed that STP-B treatment significantly upregulated macrophage M1_SIGNATURE_1 gene set, including Il6, Il1a, Cxcl9, and Cxcl10. As confirmation, we performed an ex vivo phagocytosis assay using STP-B–pretreated bone marrow-derived macrophages (BMDMs) co-cultured for 4 hours with MA9 cells and found that STP-B–treated BMDM cells showed significantly increased phagocytic activity. To assess how STP-B impacts human hematopoiesis, we transplanted CD34⁺ cord blood cells into sublethally-irradiated NSG mice and administered STP-B 8-12 weeks post-transplant. While total human CD45⁺ cellularity was unchanged, treatment markedly increased the size of myeloid (CD33⁺CD11b⁺) and monocyte (CD14⁺CD64⁺) subsets, and increased HLA-DR⁺CD86⁺ M1-like macrophages. RT-qPCR showed increased expression of myeloid transcription factors and human M1-associated genes in STP-B-treated NSG mice. We then performed metabolomic profiling of monocytic THP-1 cells, a model of myeloid differentiation, to assess intracellular NTP and dNTP levels. STP-B treatment drastically decreased intracellular CTP levels, suggesting nucleotide imbalance. Co-treatment with a ribonucleotide reductase (RNR) inhibitor partially rescued this imbalance and reversed THP-1 cell differentiation. Importantly, STP-B-mediatedupregulation of M1-associated geneswas reduced by RNR inhibition. These results support the idea that STP-B–mediated differentiation is driven by disrupted nucleotide metabolism, as we have proposed (PMID: 35439288). Moreover, GSEA indicated that STP-B treatment upregulates IFN-I-responsive genes, likely due to its DNA damage-inducing effects. CTPS1 is one of 11 glutamine amidotransferases, which catalyze histone H1 deamidation to promote DNA repair. STP-B inhibits these activities and promotes DNA damage, based on increased nuclear S9.6 staining and high γH2AX levels seen in STP-B-treated THP-1 cells. CTPS1 also deamidates IRF3, suppressing its transcriptional activity, an effect blocked by STP-B, enhancing expression of IFN-stimulatory genes (ISGs). To investigate these activities, we reconstituted CTPS1-knockout THP-1 cells with wild-type or glutaminase-deficient mutant CTPS1. Relative to wild-type CTPS1, expression of the mutant form exhibited ISG upregulation, suggesting that deamidation activity is critical to suppress IFN signaling. Together, these findings reveal that systemic STP-B treatment drives macrophage specification and innate immune activation, highlighting STP-B as a leukemia-ablating agent with immune-stimulatory potency.

Recent research highlights the pivotal function of long non-coding RNAs (lncRNAs) in bladder cancer (BCa) progression, emphasizing the need to understand their functions. The clinical significance and molecular mechanisms of lncRNA FENDRR in BCa needed to be elucidated. The Gene Expression Omnibus (GEO) database for BCa-related lncRNAs was screened. Tumor and para cancerous tissues from 118 patients with BCa were collected. Real-time quantitative polymerase chain reaction assessed FENDRR, microRNA (miR)-18a-5p, and estrogen receptor 1 (ESR1) levels. Kaplan-Meier curves assessed FENDRR's prognostic significance. Cell Counting Kit-8, Transwell, and flow cytometry evaluated cell proliferation, migration, invasion, and apoptosis. Dual-Luciferase Reporter and RNA Immunoprecipitation assays revealed miR-18a-5p targeting of FENDRR and ESR1. FENDRR exhibited differential expression in BCa GEO databases. Notably, FENDRR and ESR1 were downregulated, while miR-18a-5p was upregulated in BCa tissues and cell lines. Low FENDRR expression correlated with poor clinical prognosis. Upregulating FENDRR hindered cell proliferation, migration, and invasion while promoting apoptosis; however, miR-18a-5p reversed this suppression. Mechanistically, miR-18a-5p directly targets both FENDRR and ESR1. Our study reveals that low FENDRR expression is a poor prognostic indicator in BCa. FENDRR inhibits miR-18a-5p to upregulate ESR1 and hinder cancer progression, suggesting potential therapeutic targets.

Venetoclax (VEN), when combined with hypomethylating agents such as azacitidine (AZA), is a critical FDA-approved AML therapy for older patients unfit for intensive chemotherapy. Despite its efficacy, resistance can emerge, and response duration is short, representing an unmet clinical need. The presence of TP53 mutations in 5–10% of newly diagnosed AML cases directly associate with VEN resistance (VEN-R), although underlying mechanisms are not well understood. Aberrant purine metabolism has been seen in cells tolerant to VEN treatment, but the driver gene(s) or their functional relevance remain elusive. Recently, employing a dynamic BH3-priming CRISPR screen, we identified ADSS2, an enzyme functioning in AMP biosynthesis, as a key modulator of VEN sensitivity; ADSS2 deletion re-sensitized VEN- and MCL1i-resistant AML cells by suppressing AMPK signaling (He X et al., ASH 2023). Recently, we evaluated ADSS2 expression in two VEN-R TP53 loss-of-function Molm13 cell lines: TP53-knockout (KO) and R248Q/− isogenic cells. Both models exhibited elevated ADSS2 expressions relative to TP53 wild-type counterparts. Moreover, ADSS2 KO combined with low-dose VEN induced robust apoptosis in both models, highlighting that high ADSS2 activity promotes TP53-mutant AML phenotypes. Herein, to investigate the mechanism of ADSS2 upregulation, we first screened out 31 candidate transcription factors (TFs) associated with ADSS2 transcription through the TFBIND database. Further correlation analysis between TF and ADSS2 expression in the Beat AML cohort, followed by shRNA-mediated knockdown plus ChIP/qPCR validation, identified c-Myc as a critical regulator of ADSS2. Notably, c-Myc levels were significantly elevated in TP53-KO and TP53 R248Q/− Molm13 isogenic cells relative to respective parental counterparts. To track c-Myc-ADSS2-high cell emergence and their relationship to TP53 mutation at single-cell resolution, we utilized Genotyping of Transcriptomes (GoT) approach, which overlays TP53 mutational status onto single-cell RNA-seq data. We applied this approach to a paired TP53 mutant (c.742C>T, p.R248Q) patient-derived xenograft (PDX) sample prior- and after VEN/AZA treatment. Briefly, NSGS mice were engrafted with PDX blasts and treated with either V/A (VEN: 100mg/kg/i.g./q.d., 5 times/week, AZA: 3mg/kg/i.p./t.i.w) or vehicle until resistance developed and then bone marrow (BM) PDX cells were harvested for analysis. The frequency of genotyped blasts in either drug-naïve or post-treatment groups was approximately 83.2%, consistent with reported genotyping efficiency. Comparison of drug-naïve with resistant PDX cells revealed markedly increased ADSS2 and c-Myc expression in the resistant state. Genotype overlay on transcriptome maps showed that TP53-mutant cells expressed significantly higher levels of ADSS2 and c-Myc than did TP53-wild-type cells in drug-naïve samples. Notably, at relapse, the TP53-mut population expanded from 37.5% to 63.2%, contributing to c-Myc and ADSS2 upregulation in resistant samples. These results suggest that ADSS2 upregulation in resistant cells is associated with clonal selection of pre-existing TP53-mutant cells exhibiting elevated c-Myc and ADSS2 levels. We next assessed the therapeutic potential of Cmpd3, our newly developed ADSS2 inhibitor, as monotherapy or combined with V/A in NSGS mice engrafted with a TP53-mutant AML PDX. After confirming engraftment, we treated mice 3 weeks with vehicle, Cmpd3 (100 mg/kg, intraperitoneally, once daily, five times per week), V/A, or Cmpd3 plus V/A. Analysis of BM samples revealed that combination therapy significantly decreased the leukemic burden compared to either monotherapy, indicating a synergistic anti-leukemic effect in this TP53-mutant AML model. We also assessed the impact of Cmpd3 on normal hematopoiesis in WT C57BL/6 mice. Mice treated for 4 weeks with Cmpd3 showed no significant changes in organ (kidney, liver, spleen) histology, body weight, or HSPC frequency, and only modestly decreased numbers of BM B and T cells, indicating relative safety of Cmpd3. Collectively, our study reveals ADSS2 to be a contributor to TP53-associated VEN resistance and a promising target to restore drug sensitivity in this high-risk AML subtype.

BACKGROUND: Hyperglycemia and insulin resistance are among the key phenotypes of obesity and type 2 diabetes (T2DM). Notably, skeletal muscle fiber-type composition is closely linked to insulin resistance. Vascular endothelial growth factor B (VEGF-B) has been shown to play an important role in T2DM. However, the effects of VEGF-B on myofiber types in individuals with obesity or T2DM remain unclear. This study aimed to investigate the effects and mechanisms of VEGF-B on myofiber-type formation and regeneration. METHODS: Male Vegfb (vascular endothelial growth factor B) gene knockout mice and wild-type C57BL/6 male mice were fed either a normal diet or a high-fat diet. Double immunofluorescence staining and RNA-seq of skeletal muscle tissue from these mice were used to evaluate the role of VEGF-B in myofiber type regulation. To investigate the effects of VEGF-B on myoblast differentiation, fusion, and type I slow-twitch fiber formation in vitro, we prepared a novel in vitro model by continuous single-dose administration of VEGF-B, which was matched with physiological conditions and high-fat diet-induced hyperglycemia in vivo. RESULTS: VEGF-B deficiency attenuated high-fat diet-induced loss of slow-twitch type I myofibers and improved hyperglycemia and insulin resistance in mice. Continuous low-concentration administration of VEGF-B isoforms (VEGF-B186 and VEGF-B167) enhanced myoblast differentiation, fusion and myotube formation in a dose-dependent manner, whereas higher concentrations inhibited these processes, with VEGF-B186 exhibiting more pronounced effects. Notably, elevated VEGF-B levels, particularly VEGF-B186, suppressed mainly slow-twitch type I myofiber formation. Mechanistic studies revealed that high-dose VEGF-B186 (100 ng/mL) reduced myoblast differentiation/fusion and slow-twitch fiber formation via PKA-NFAT-MyoG/MEF2C signaling. Furthermore, high-dose VEGF-B186 decreased the expression of glucose transporter type 4, glucose utilization, and mitochondrial function in a unique myoblast cell model, effects that were reversed by PKA activators and NFATc1/c2 overexpression. CONCLUSION: These findings demonstrate that VEGF-B is a key regulator of myofiber type composition and metabolic homeostasis in the context of obesity or T2DM. The inhibitory effects of elevated VEGF-B186 on slow-twitch fiber formation and glucose metabolism underscore its pathological role in obesity-related metabolic dysregulation. These results support the therapeutic potential of targeting VEGF-B186—via inhibitors or monoclonal antibodies— for obesity and T2DM, which are characterized by slow-twitch fiber depletion.

ABSTRACT Objective Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD. Methods We utilized time‐of‐flight mass cytometry (CyTOF) with single‐cell resolution to quantitatively analyze peripheral PBMCs, identifying 1228 immune characteristics. Based on the top‐selected immune features, we constructed immunological elastic net (iEN) models. Results These models demonstrated high diagnostic efficacy in distinguishing diseased samples from healthy donors as well as distinguishing AD and DLB cases. The selected features reveal that the primary peripheral immune characteristic of AD is a decrease in total T cells, while DLB is characterized by low expression of I‐kappa‐B‐alpha (IKBα) in the classical monocyte subset. Conclusions These findings suggest that peripheral immune characteristics could serve as potential biomarkers, facilitating the diagnosis of neurodegenerative diseases.

[This corrects the article DOI: 10.3389/fendo.2025.1662731.].

Gastric cancer (GC) is a leading cause of cancer-related mortality, particularly in East Asia, where its incidence remains high. The limited prognosis for advanced GC patients underscores the need for new therapeutic strategies targeting key molecules involved in tumor progression. In this study, we investigated the role of the deubiquitinating enzyme USP47 in GC progression, focusing on its interaction with Neuropilin-1 (NRP1), a co-receptor known to enhance angiogenesis. Our findings reveal that USP47 is significantly overexpressed in GC tissues and correlates with poor patient survival. Through in vitro experiments, we demonstrate that USP47 promotes GC cell proliferation, migration, and invasion. Additionally, USP47 enhances angiogenesis by stabilizing NRP1, preventing its ubiquitination and degradation, and activating the PI3K/Akt signaling pathway. These results suggest that USP47 contributes to GC progression through the regulation of NRP1-mediated angiogenesis, highlighting its potential as a therapeutic target for GC treatment.

With the rapid development of electronic technology and the wide application of 5G networks, flexible electronic devices with a single function can't meet the needs of daily life or military fields. Inspired by the structure of coral reefs, a high-performance polyurethane composite elastomer was designed for multifunctional applications, which was enhanced by multi-dimensional coral reef-like hierarchical heterostructures consisting of MXene, carbon nanotubes (CNTs), and Fe3O4 via a solvothermal method. The composite elastomer reached a minimum reflection loss (RLmin) of -54.81 dB and worked effectively from -20 to 100 degrees C, which could meet the needs of year-round electromagnetic protection. Also, it showed a good sensitivity with a high GF value of 608, which could be widely used in flexible sensing and human motion monitoring. More importantly, its thermal diffusion capability was 155.9 % higher than that of pure polyurethane, and it remained stable at 200 degrees C and was not easy to decompose, showing outstanding thermal transmission and thermal stability. Such a novel functional composite material will provide an effective guidance solution for electromagnetic protection, flexible sensing, and thermal management under complex working conditions.

The prevalence of urological malignancies continues to pose a significant global health challenge, particularly due to the poor prognosis associated with advanced stages of these diseases. Consequently, there is an urgent need to deepen our understanding of the molecular mechanisms governing the development of urological malignancies to facilitate breakthroughs in diagnosis and treatment. Pyroptosis, a novel and specific form of programmed cell death, plays a crucial role in regulating inflammatory responses, cell development, tissue homeostasis, and stress responses. Recent research has revealed a close association between pyroptosis and urological malignancies. In this paper, we review the pathogenesis and recent advancements in the understanding of pyroptosis in urological malignancies, elucidate the molecular mechanisms involved in its regulation, and aim to provide new directions for the clinical management of these diseases.

The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases. Targeted black phosphorus nanosheet-based therapeutics that efficiently deliver resolvin D1 to lesional macrophages for the treatment of atherosclerosis by reducing oxidative stress and resolving inflammation have been discussed.

A major obstacle to exploiting industrial flue gas for microalgae cultivation is the unfavorable acidic environment. We previously identified three upregulated genes in the low-pH-adapted model diatom Phaeodactylum tricornutum: ferredoxin (PtFDX), cation/proton antiporter (PtCPA), and HCO3 - transporter (PtSCL4-2). Here, we individually overexpressed these genes in P. tricornutum to investigate their respective roles in resisting acidic stress (pH 5.0). The genetic modifications enabled positive growths of transgenic strains under acidic stress that completely inhibited the growth of the wild-type strain. Physiological studies indicated improved photosynthesis and reduced oxidative stress in the transgenic strains. Transcriptomes of the PtCPA- and PtSCL4-2-overexpressing transgenics showed widespread upregulation of various transmembrane transporters, which could help counteract excessive external protons. This work highlights ion/electron carrier genes' role in enhancing diatom resistance to acidic stress, providing insights into phytoplankton adaptation to ocean acidification and a strategy for biological carbon capture and industrial flue gas CO2 utilization.

The silicifying peptide R5 (H‐SSKKSGSYSGSKGSKRRIL‐OH) derived from diatoms is extensively investigated, but the mechanism underlying silica synthesis by R5 or R5‐alike peptides is still poorly understood, limiting the design of silicifying peptides Herein, machine learning techniques are used to design peptides with silicifying functionality. Utilizing a comprehensive dataset of peptides and their corresponding silicification outcomes, a deep learning model based on antimicrobial peptide migration learning is created. This model exhibits the remarkable capability to accurately predict peptide sequences with a high potential for facilitating silica formation. A selection of artificially designed peptides can catalyze the biomimetic synthesis of nanosilica, some of which demonstrate better catalytic activity with a wider pH range and faster reaction rate compared with the peptide R5. Additionally, the designed peptide is used to wrap the model diatom Phaeodactylum tricornutum with nanosilica coatings, resulting in a significant enhancement in the UV resistance of cells. The new silicified peptides are highly significant for advancing the understanding of the silica synthesis mechanism in diatoms, and the encapsulation of P. tricornutum has potential benefits in the development of new biosensors.

Objective:To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.Methods:Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.Results:All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.Conclusion:The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and INa+/IK+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

A 36-year-old healthy male patient was presented to the emergency room 3 h after experiencing a laceration to the left foot caused by a porcelain shard. The defect measured 7.5 × 6.0 × 0.8 cm, and the composite amputated tissue consisted of skin and subcutaneous layers. The terminal branch of the lateral calcaneal artery was first anastomosed end-to-end to the corresponding artery in the wound defect. The lateral calcaneal nerve was anastomosed after blood flow was restored. The two lateral veins were anastomosed end-to-end to the corresponding veins in the wound defect. Postoperatively, 1.0 × 1.5 cm area of skin necrosis was present at the distal end of the tissue, which healed smoothly after two weeks of dressing changes. The patient had retained excellent aesthetic and functionality by the 37 month follow up. Although such isolated amputation is relatively rare, microsurgical replantation is, thus, a feasible option in the management of heel amputation.