DNA large fragment deleting by compact, sequence-motif-free and specific TaqTth-hpRNA assisted with the microhomology-mediated end joining pathway.

A DNA editing tool TaqTth-hpRNA was developed in this study, composed of a compact recombinant TaqTth nuclease (832 aa) and a simple hairpin-RNA guiding probe (hpRNA). In vitro biochemical studies showed the TaqTth-hpRNA efficiently cleaves artificially synthesized single-stranded DNA without stringent sequence motif like protospacer adjacent motif (PAM). It can also cleave the genomic DNA of Escherichia coli with ∼80% efficiency.

Activation of Lysosomal Retrograde Transport Triggers TPC1-IP3R1 Ca Crosstalk at Lysosome-ER MCSs Leading to Lethal Depleting of ER Calcium.

Inter-organellar signaling linkages in oncology are increasingly elucidated. However, the impact of lysosome-endoplasmic reticulum (ER) interaction on tumor cell fate remains relatively unexplored. A novel interaction between lysosomes and the ER, mediated by the flavonoid LW-213 through targeting LIMP2 (lysosomal integral membrane protein type 2)to activate a lysosomal repair pathway, is identified in acute myeloid leukemia (AML).

[Explanation and interpretation of blood transfusion provisions for children undergoing cardiac surgery in the national health standard "Guideline for pediatric transfusion"].

To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery.

Therapeutic Effect of V8 Affecting Mitophagy and Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Mediated by ROS and CHOP Signaling.

Acute myeloid leukemia (AML) is characterized by the malignant proliferation of abnormally or poorly differentiated myeloid cells in the hematopoietic system. However, there is a lack of effective drugs for treating non-M3 AML. V8, a newly synthesized derivative of the natural flavonoid wogonin, which is a potential anticancer drug, has demonstrated significant antitumor activity both in vitro and in vivo.

Identification of an elusive deletion in a family with hereditary angioedema type I utilizing soft clipping.

Background: Hereditary angioedema (HAE) is an autosomal dominant genetic disorder caused by mutations in the C1 esterase inhibitor gene, SERPING1, leading to overproduction of bradykinin and debilitating swelling attacks. Variants in the gene are typically detected in a clinical setting by DNA sequencing or multiplex ligation-dependent probe amplification (MLPA), with over 893 total variants identified. Approximately 5% of patients with C1-esterase inhibitor deficiencies do not have detectable pathogenic variants.

[Explanation and interpretation of blood transfusion provisions for critically ill and severely bleeding pediatric patients in the national health standard "Guideline for pediatric transfusion"].

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock.

Inhibition of Rho GEFs attenuates pulmonary fibrosis through suppressing myofibroblast activation and reprogramming profibrotic macrophages.

Idiopathic pulmonary fibrosis has a poor prognosis, with existing medications only partially alleviating symptoms, highlighting the urgent need for new therapeutic approaches. The dysregulations of Rho GTPases/ROCK are related with various diseases, including fibrosis. Nevertheless, the development of drugs for pulmonary fibrosis treatment has predominantly concentrated on ROCK inhibitors.

Acid-responsive engineered bacteria with aberrant In-Situ anti-PD-1 expression for post-ablation immunotherapy of hepatocellular carcinoma.

Local thermal ablation (TA) can not only reduce the tumor burden of hepatocellular carcinoma (HCC) but also stimulate the host anti-tumor immune response, offering a promising avenue for combination with immune checkpoint blockade (ICB). However, tumor recurrence and ICB resistance are associated with residual tumor masses caused by incomplete TA treatment. Thus, adjuvant therapy that can accurately eliminate residual HCC tumors post-TA is expected to improve prognosis.

FV-429 suppresses cancer cell migration and invasion by EMT via the Hippo/YAP1 pathway in pancreatic cancer cells.

Pancreatic cancer is one of the most common malignant tumors of the digestive system, with the majority of patients not succumbing to the primary tumor but rather to metastasis. Epithelial-mesenchymal transition (EMT) is abnormally activated in numerous cancers, whereby it promotes tumor cell migration and invasion. Yes-associated protein 1 (YAP1) is commonly overexpressed in various cancer types and plays an oncogenic role.

[Explanation and interpretation of the compilation of blood transfusion provisions for children undergoing hematopoietic stem cell transplantation in the national health standard "Guideline for pediatric transfusion"].

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children.

Donafenib combined with sintilimab for advanced hepatocellular carcinoma: a single arm phase II trial.

Background: Previous studies evaluating antiangiogenic agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma (HCC) have shown encouraging results. This study was conducted to investigate the efficacy and safety of donafenib combined with sintilimab (Don-Sin) for advanced HCC.

Methods: This was a single-center, single-arm phase II trial recruiting patients with BCLC stage C HCC.

[Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion"].

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura.

[Explanation and interpretation of the compilation of neonatal blood transfusion in the national health standard "Guideline for pediatric transfusion"].

In order to guide clinical blood transfusion practices for pediatric patients, the National Health Commission has released the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Considering the physiological particularities of the neonatal period, blood transfusion practices for neonates are more complex than those for other children, the guidelines include a separate chapter dedicated to neonatal blood transfusion. This paper interprets the background and evidence for the compilation of the neonatal blood transfusion provisions, hoping to aid in the understanding and implementation of the neonatal blood transfusion section of the guidelines.

GL-V9 Promotes Autophagy-Mediated YAP1 Degradation and Activates Mitochondrial Apoptosis in PDAC Cells.

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive forms of pancreatic cancer with a poor prognosis. YAP1 expression is markedly elevated in PDAC, but how it works is not clear. GL-V9, a derivative of the natural compound wogonin, effectively fights a variety of tumors; however, its effect on PDAC has not yet been studied.

Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion: A case report.

Background: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume.

Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomes.

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs).

Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension.

Background & Aims: Cirrhotic portal hypertension (CPH) is the leading cause of mortality in patients with cirrhosis. Over 50% of patients with CPH treated with current clinical pharmacotherapy still present variceal bleeding or sometimes death owing to insufficient reduction in portal pressure. Elevated intrahepatic vascular resistance (IHVR) plays a fundamental role in increasing portal pressure.

TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically.

FV-429 induces apoptosis by regulating nuclear translocation of PKM2 in pancreatic cancer cells.

Of all malignancies, pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, has the worst prognosis. Glycolysis is overactive in PDAC patients and is associated with poor prognosis. Drugs that inhibit glycolysis as well as induce cell death need to be identified.

GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism.

Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20-30% of PCa cases develop into castration-resistant prostate cancer (CRPC).

Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study.

Background & Aims: Our retrospective study has suggested encouraging outcomes of lenvatinib combined with PD-1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy and safety of lenvatinib, sintilimab (a PD-1 inhibitor) plus TACE (Len-Sin-TACE) in patients with advanced stage HCC.

Methods: This was a single-arm phase II trial.