AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress.

Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B accounts for glycerol biosynthesis by forming a complex with glycerol 3-phosphate dehydrogenases GPD1 and GPD1L.

Campaign Governance and Playfulness: Unraveling Chinese HPV Immunization Promotion Efforts on Douyin.

(1) Background: Playful immunization promotion helps to approach persuasive efforts and raise vaccine acceptance. However, playful promotion in the field of HPV immunization has not been explored. (2) Methods: To address this gap, we analyzed data gleaned from 73 short videos posted by state media and from semi-structured interviews with 37 Chinese stakeholders using thematic analysis.

Hypoxia-induced downregulation of PGK1 crotonylation promotes tumorigenesis by coordinating glycolysis and the TCA cycle.

Protein post-translational modifications (PTMs) are crucial for cancer cells to adapt to hypoxia; however, the functional significance of lysine crotonylation (Kcr) in hypoxia remains unclear. Herein we report a quantitative proteomics analysis of global crotonylome under normoxia and hypoxia, and demonstrate 128 Kcr site alterations across 101 proteins in MDA-MB231 cells. Specifically, we observe a significant decrease in K131cr, K156cr and K220cr of phosphoglycerate kinase 1 (PGK1) upon hypoxia.

Connecting efficiency and responsiveness in China: public sentiments and stakeholder perspectives towards COVID-19 crisis governance.

The COVID-19 (coronavirus disease 2019) pandemic initiated debates on how crisis management affects democracy. In them, the balance between deploying control strategies that limit citizens' freedom and their democratic legitimation features prominently. Informed by theoretical debates about responsive crisis governance, this paper explores how Chinese citizens reacted by quantitatively and qualitatively analysing social media expressions and Chinese stakeholders' narratives.

An assessment of AcquireX and Compound Discoverer software 3.3 for non-targeted metabolomics.

We used the Exploris 240 mass spectrometer for non-targeted metabolomics on Saccharomyces cerevisiae strain BY4741 and tested AcquireX software for increasing the number of detectable compounds and Compound Discoverer 3.3 software for identifying compounds by MS spectral library matching. AcquireX increased the number of potentially identifiable compounds by 50% through six iterations of MS acquisition.

Indole Alkaloid Production by the Halo Blight Bacterium Treated with the Phytoalexin Genistein.

When pv. , the bacterium that causes halo blight, induces hypersensitive immunity in common bean leaves, salicylic acid and phytoalexins accumulate at the site of infection. Both salicylic acid and the phytoalexin resveratrol exert antibiotic activities and toxicities in vitro, adversely disrupting the pv.

Campaign Governance and Partnerships: Unraveling COVID-19 Vaccine Promotion Efforts in China's Neighborhoods.

Background: COVID-19 vaccine promotion helps counter vaccine hesitancy and raise vaccine acceptance. Therefore, the Chinese state created collaborative infrastructures of COVID-19 vaccine promotion programs to promote stakeholder engagement and unload the burden of policy practitioners. However, partnerships in COVID-19 vaccine promotion programs have been underrepresented.

Unfolding COVID-19 vaccine communication campaigns in China's neighborhoods: a qualitative study of stakeholders' narratives.

Introduction: The Chinese state has recently implemented the COVID-19 Vaccine Communication Campaign (CVCC) to counter vaccine hesitancy. Nonetheless, the extant literature that examines COVID-19 vaccine acceptance has less represented COVID-19 vaccine communication efforts.

Methods: To address this lacuna, we qualitatively explored how CVCCs were organized in Chinese communities by investigating 54 Chinese stakeholders.

HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.

The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components.

De novo pyrimidine biosynthetic complexes support cancer cell proliferation and ferroptosis defence.

De novo pyrimidine biosynthesis is achieved by cytosolic carbamoyl-phosphate synthetase II, aspartate transcarbamylase and dihydroorotase (CAD) and uridine 5'-monophosphate synthase (UMPS), and mitochondrial dihydroorotate dehydrogenase (DHODH). However, how these enzymes are orchestrated remains enigmatical. Here we show that cytosolic glutamate oxaloacetate transaminase 1 clusters with CAD and UMPS, and this complex then connects with DHODH, which is mediated by the mitochondrial outer membrane protein voltage-dependent anion-selective channel protein 3.

Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation.

The roles of lamin A/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A/C levels at serine 22 or 392 sites (pLamin A/C-S22/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells).

Repurposing a tricyclic antidepressant in tumor and metabolism disease treatment through fatty acid uptake inhibition.

Fatty acid uptake is essential for cell physiological function, but detailed mechanisms remain unclear. Here, we generated an acetyl-CoA carboxylases (ACC1/2) double-knockout cell line, which lacked fatty acid biosynthesis and survived on serum fatty acids and was used to screen for fatty acid uptake inhibitors. We identified a Food and Drug Administration-approved tricyclic antidepressant, nortriptyline, that potently blocked fatty acid uptake both in vitro and in vivo.

Stearate-derived very long-chain fatty acids are indispensable to tumor growth.

Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains unclear. While previous studies have focused on involvement of long-chain fatty acids (LCFAs) including palmitate in cancer, little attention has been paid to the role of very long-chain fatty acids (VLCFAs). Here, we show that depletion of acetyl-CoA carboxylase (ACC1), a critical enzyme involved in the biosynthesis of fatty acids, inhibits both de novo synthesis and elongation of VLCFAs in human cancer cells.

Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress.

An enhanced NADH/NAD ratio, termed reductive stress, is associated with many diseases. However, whether a downstream sensing pathway exists to mediate pathogenic outcomes remains unclear. Here, we generate a soluble pyridine nucleotide transhydrogenase from Escherichia coli (EcSTH), which can elevate the NADH/NAD ratio and meantime reduce the NADPH/NADP ratio.

METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions.

The methyltransferase like 3 (METTL3) has been generally recognized as a nuclear protein bearing oncogenic properties. We find predominantly cytoplasmic METTL3 expression inversely correlates with node metastasis in human cancers. It remains unclear if nuclear METTL3 is functionally distinct from cytosolic METTL3 in driving tumorigenesis and, if any, how tumor cells sense oncogenic insults to coordinate METTL3 functions within these intracellular compartments.

Compound 968 reverses adriamycin resistance in breast cancer MCF-7 cells via inhibiting P-glycoprotein function independently of glutaminase.

Adriamycin (ADR) is a chemotherapeutic drug widely utilized to treat multiple types of cancers; however, the clinical efficacy of ADR is compromised due to the development of drug resistance in patients. The combination of drugs with ADR may provide a better therapeutic regimen to overcome this obstacle. Glutaminase (GLS) has been explored as a therapeutic cancer target, and its inhibition also results in increased sensitivity of tumor cells to chemotherapeutic agents.

Potential of electron transfer and its application in dictating routes of biochemical processes associated with metabolic reprogramming.

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism.

SY-1530, a highly selective BTK inhibitor, effectively treats B-cell malignancies by blocking B-cell activation.

Objective: B-cell antigen receptor (BCR) signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies. Bruton tyrosine kinase (BTK), a critical mediator of BCR signaling, is an attractive target for the treatment of B-cell malignancies. This study aimed to identify a highly potent and selective BTK inhibitor.

Bacterial Immobilization and Toxicity Induced by a Bean Plant Immune System.

pv. causes halo blight disease in the common bean . The bacterium invades the leaf apoplast and uses a type III secretion system to inject effector proteins into a bean cell to interfere with the bean immune system.

Downregulation of contributes to prostate cancer cell invasion and TGFβ1-induced EMT.

Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients.

Genomic Resources for pv. Races 5 and 8.

pv. causes halo blight disease on . Using a long-read DNA sequencing platform, we assembled the genome sequences for pv.

Vaccine Hesitancy in China: A Qualitative Study of Stakeholders' Perspectives.

A series of vaccine incidents have stimulated vaccine hesitance in China over the last decade. Many scholars have studied the institutional management of these incidents, but a qualitative study of stakeholders' perspectives on vaccine hesitancy in China is missing. To address this lacuna, we conducted in-depth interviews and collected online data to explore diverse stakeholders' narratives on vaccine hesitance.