Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization.

Background: To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways.

Methods: We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA ( = 437,354) with any stroke (AS, FinnGen:  = 311,635; MEGASTROKE:  = 446,696), ischemic stroke (IS, FinnGen:  = 212,774; MEGASTROKE:  = 440,328), intracranial hemorrhage (ICH, FinnGen:  = 343,663; ISGC:  = 3,026), functional outcome after ischemic stroke at 90d ( = 4,363), and motor recovery within 24 months after stroke ( = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders.

Modifiable risk factors mediate the effect of gastroesophageal reflux disease on stroke and subtypes: A Mendelian randomization study.

Objectives: Previous observational studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of stroke, but the specific underlying mechanisms are unclear. We investigated the causal associations of GERD with stroke and its subtypes using Mendelian randomization (MR), and evaluated the potential mediating effects of modifiable stroke risk factors in the causal pathway.

Methods: Genetic instrumental variables for GERD were extracted from the latest genome-wide association study (GWAS) summary level data.

Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells.

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress.

Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.

Human epidermal growth factor receptor 2-targeted (HER2-targeted) therapy is the mainstay of treatment for HER2+ breast cancer. However, the proteolytic cleavage of HER2, or HER2 shedding, induces the release of the target epitope at the ectodomain (ECD) and the generation of a constitutively active intracellular fragment (p95HER2), impeding the effectiveness of anti-HER2 therapy. Therefore, identifying key regulators in HER2 shedding might provide promising targetable vulnerabilities against resistance.

Minimum taxi fleet algorithm considering human spatiotemporal behaviors.

With the development of information technology, more and more travel data have provided great convenience for scholars to study the travel behavior of users. Planning user travel has increasingly attracted researchers' attention due to its great theoretical significance and practical value. In this study, we not only consider the minimum fleet size required to meet the urban travel needs but also consider the travel time and distance of the fleet.

A Wnt-induced lncRNA-DGCR5 splicing switch drives tumor-promoting inflammation in esophageal squamous cell carcinoma.

Alternative splicing (AS) is a critical mechanism for the aberrant biogenesis of long non-coding RNA (lncRNA). Although the role of Wnt signaling in AS has been implicated, it remains unclear how it mediates lncRNA splicing during cancer progression. Herein, we identify that Wnt3a induces a splicing switch of lncRNA-DGCR5 to generate a short variant (DGCR5-S) that correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC).

The phospholipid flippase ATP9A enhances macropinocytosis to promote nutrient starvation tolerance in hepatocellular carcinoma.

Macropinocytosis is an effective strategy to mitigate nutrient starvation. It can fuel cancer cell growth in nutrient-limited conditions. However, whether and how macropinocytosis contributes to the rapid proliferation of hepatocellular carcinoma cells, which frequently experience an inadequate nutrient supply, remains unclear.

BAG2 drives chemoresistance of breast cancer by exacerbating mutant p53 aggregate.

Chemoresistance is a major challenge in the clinical management of patients with breast cancer. Mutant p53 proteins tend to form aggregates that promote tumorigenesis in cancers. We here aimed to explore the mechanism for the generation of mutant p53 aggregates in breast cancer and assess its role in inducing chemoresistance.

USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer.

Indoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC).

MEX3C-Mediated Decay of SOCS3 mRNA Promotes JAK2/STAT3 Signaling to Facilitate Metastasis in Hepatocellular Carcinoma.

Unlabelled: Tumor metastasis is one of the major causes of high mortality in patients with hepatocellular carcinoma (HCC). Sustained activation of STAT3 signaling plays a critical role in HCC metastasis. RNA binding protein (RBP)-mediated posttranscriptional regulation is involved in the precise control of signal transduction, including STAT3 signaling.

The mechanism of AMPA receptor subunit GluR1 in electroacupuncture treatment of acute spinal cord injury in rats.

Glutamate excitotoxicity plays a role in spinal cord injury (SCI). This study aimed to explore whether electroacupuncture (EA) improved the functional recovery of spinal cord anterior horn neurons of rats with acute SCI by regulating the GluR1 AMPA subunit in the SCI area. Eighty Sprague-Dawley rats were randomly divided into 5 groups: sham operation, model, AMPA antagonist (DNQX), EA and DNQX + EA group (n = 16/group).

Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer.

Nicotine addiction and the occurrence of lymph node spread are two major significant factors associated with esophageal cancer's poor prognosis; however, nicotine's role in inducing lymphatic metastasis of esophageal cancer remains unclear. Here we show that OTU domain-containing protein 3 (OTUD3) is downregulated by nicotine and correlates with poor prognosis in heavy-smoking esophageal cancer patients. OTUD3 directly interacts with ZFP36 ring finger protein (ZFP36) and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination.

The mechanism of AMPA receptor subunit GluR1 in electroacupuncture treatment of acute spinal cord injury in rats.

Glutamate excitotoxicity plays a role in spinal cord injury (SCI). This study aimed to explore whether electroacupuncture (EA) improved the functional recovery of spinal cord anterior horn neurons of rats with acute SCI by regulating the GluR1 AMPA subunit in the SCI area. Eighty Sprague-Dawley rats were randomly divided into 5 groups: sham operation, model, AMPA antagonist (DNQX), EA and DNQX+EA group (n=16/group).

Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer.

Balancing mRNA nuclear export kinetics with its nuclear decay is critical for mRNA homeostasis control. How this equilibrium is aberrantly disrupted in esophageal cancer to acquire cancer stem cell properties remains unclear. Here we find that the RNA-binding protein interleukin enhancer binding factor 2 (ILF2) is robustly upregulated by nicotine, a major chemical component of tobacco smoke, via activation of JAK2/STAT3 signaling and significantly correlates with poor prognosis in heavy-smoking patients with esophageal cancer.

ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer.

Background: Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.

[Corrigendum] GINS2 is a novel prognostic biomarker and promotes tumor progression in early‑stage cervical cancer.

Subsequently to the publication of the above article, the authors have realized that Figs. 2 and 6 each contained an incorrectly assembled data panel: Essentially, a couple of the data panels had been inadvertently selected twice for these figures. The corrected versions of Figs 2 and 6, including the correct data for the H&E staining of the tissue of patient 4 in Fig.

[Influence of electroacupuncture on the expression of AMPA receptor subunit GluR1 in the spinal injured area of the rats with acute spinal cord injury].

Objective: To explore the influence of electroacupuncture (EA) on the expression of AMPA receptor subunit GluR1 in the rats with acute spinal cord injury (SCI) and explore the potential effect mechanism of EA in treatment of acute SCI.

Methods: A total of 80 SD rats were randomly divided into five groups, i.e.