• TGF-β1 expression, fibroblast proliferation and ECM deposition are increased in lymphedematous skin.
• Tissue lysate of lymphedematous skin induces fibroblast proliferation, ECM production and increases the stiffness of fibroblasts, LECs and LSMCs.
• Inhibition of TGF-β1 decreases ECM deposition, immune cell infiltration and increases collateral lymphatics formation.
• Topical treatment of pirfenidone is highly effective for lymphedema treatment.

1. UGRP1–PDPN signalling activate RhoA to enhance the interaction of IKKγ and IKKβ.

2. Interaction of IKKγ and IKKβ activate NF-κB to enhance expression of TLR2, MyD88 and NOD2.

3. Upon S. pneumoniae infection, increased expression of TLR2, MyD88 and NOD2 could generate enhanced NF-κB signalling to produce more pro-inflammatory cytokines including IL-6, IL-1β and TNFα.

• The EASY prediction score is a practical tool for identifying patients at a greater risk for severe acute pancreatitis shortly after hospital admission.
• The explanation of the impact of features on the prediction helps physicians understand the decision of the machine learning model.
• The easy-to-use web application is available for clinicians and contributes to the improvement of the model.

• Long-term lifestyle habits including diet, physical activity, smoking and alcohol consumption jointly shape epigenetic patterns and affect methylation age.
• These effects clearly dominate over those driven by age and obesity alone.
• An interplay of lifestyle aspects needs to be considered when analysing epigenetic data with regard to complex metabolic diseases.

• Genome-wide CRISPRCas9 screening identified MDM2 as a potential target for wtT53-RTK NSCLC cells.
• MDM2 inhibitor RG7388 selectively kill wtT53-RTK cells but is less effective against NSCLC cells carrying other genotypes.
• RG7388 and pemetrexed worked synergistically in blocking proliferation and tumor growth of wtT53-RTK NSCLC.

1. NNMT is highly expressed in ccRCC primary tumours and metastases, correlating with worse patient survival.
2. Glutamine metabolism is impaired in NNMT-depleted cells, with negative consequences for cellular fitness.
3. NNMT inhibition reduces cell viability and induces cytotoxicity in 2D/3D ccRCC-derived tumour models.
4. Beyond NNMT inhibition for the treatment of metabolic diseases, its application for anticancer therapy appears promising.

1. TLR4 and DDX3X are upregulated after SCI in mice.

2. TLR4 deficiency alleviated DDX3X-dependent NLRP3 inflammasome activation and microglial pyroptosis after SCI in mice.

3. TLR4 interacts with BGN and jointly promotes STAT1-dependent transcriptional activation of DDX3X by activating the JAK2/STAT1 pathway after SCI in mice.

• CAR NK-92 is activated through specific recognition of PSMA on prostate cancer cells.
• Expression of PD-L1 on activated CAR NK-92 is upregulated via CAR-triggered PI3K/AKT/mTOR pathway.
• Expression of PD-L1 on cancer cells is upregulated via IFN-γ-mediated JAK-STAT pathway.
• Atezolizumab potentiates CAR NK-92 cytotoxicity by directly acting on PD-L1 on CAR NK-92 and unleashes CD8⁺ T cell via blocking PD-L1/PD-1 axis.

1. STARD3, upregulated in COPD, could help cholesterol transfer to mitochondria and lead to mitochondrial dysfunction.
2. Exogenous cholesterol reversed the protective MFN2 upregulation in CSE stimulation and exacerbated the mitochondrial dysfunction.
3. Mitochondrial dysfunction caused by MFN2 downregulation altered the lipid homeostasis related to the activation of mTOR.

• Integrated analysis of characteristics of CSF tumour environment of LM patients.
• Five subtype-specific CSF-CTCs of breast cancer showed great heterogeneities on cell proliferation and cancer-testis antigens expression.
• Gene regulatory networks (GRNs) highlighted transcription factor SREBF2 activated in the breast cancer CSF-CTCs

1. ZNF677 is frequently silenced via m⁶A modification in RCC.

2. The m⁶A modified CDS of ZNF677 positively regulates its translation and stability via binding with YTHDF1 and IGF2BP2, respectively.

3. ZNF677 exerted its tumor suppressor functions in RCC cells through transcriptional repression of CDKN3 via binding to its promoter.

• YTHDF2 is upregulated in ICC tissues, particularly in chemoresistant ICC tissues, and correlated with poor prognosis.
• Overexpression of YTDHF2 promotes ICC cell proliferation, inhibits apoptosis and accelerates cell cycle.
• Overexpression of YTHDF2 desensitised ICC cells to cisplatin treatment
• YTHDF2 facilitates ICC progression and desensitised cisplatin treatment by downregulating CDKN1B expression in an m⁶a dependent manner.

• Multi-omics characteristics of Macao elderly susceptible to neurocognitive disorders (NCDs) were investigated.
• Gut microbiota, faecal metabolites and urine exosomes were detected utilizing metagenomics, metabolomic and proteomic.
• Disturbed glyoxylate and dicarboxylate metabolism (bacteria), vitamin digestion and absorption and tricarboxylic acid cycle can serve as predictors of NCDs risk.

1. Hi-C analysis of meiotic chromatin architecture during FGSC development.

2. TADs were attenuated and then disappeared during FGSC development.

3. X chromosome shows unique chromatin architecture during FGSC development.

The immunosuppressive TME of these 3D models contained of tumour cells, CAFs and immune cells accompanied by high expression of PD-L1, PD-L2 and reduced expression of MICA/B. The immune checkpoint inhibitors and epigenetic modifiers enhance the efficacy of γδ T cells against 3D models. These four 3D models provided valuable preclinical platforms to test γδ T cell functions for immunotherapy.

• Prevotella, Gemmiger, and Roseburia were significantly upregulated at the genus level in NSCLC patients.
• Nervonic acid/all-trans-retinoic acid was negatively related to Prevotella.
• CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC.
• Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient mice caused inflammation and immune dysregulation in Lewis lung cancer (LLC) cells-bearing C57BL/6 mice.
• Nervonic acid/all-trans-retinoic acid improved the Prevotella copri-treated LLC cells-bearing C57BL/6 mice phenotype.

1. Identified a lipid metabolism related lncRNA SLC25A21-AS1 which can be downregulated by HFD/PA.
2. LncRNA SLC25A21-AS1 promotes proliferation and migration of ESCC cells through the NPM1/c-Myc axis and elevation of SLC25A21 expression.
3. LncRNA SLC25A21-AS1 is associated with overall survival and tumor grade.

(1) The heart-enriched lncR-SMAL is robustly increased in its level in serum samples of human subjects over 60-year old relative to young controls, and in both nucleus and cytoplasm of senescent cardiomyocytes. (2) Artificial overexpression of lncR-SMAL induces cardiac senescence by inhibiting Parkin-mediated mitophagy. Knockdown of endogenous lncR-SMAL in cardiomyocytes partially abrogated cell senescence. (3) LncR-SMAL interacts with Parkin protein and promotes ubiquitin-proteasome degradation of Parkin in senescent cardiomyocytes.

1. Rapid regulation of neurotransmitters in islet is exerted by altering proteins phosphorylation rather than expression levels.
2. Proteins phosphorylation modulated by kinases play an important role in neurotransmitters ACh and NE mediated islet hormones secretion.
3. Impaired innervation and aberrant rhythm of insulin secretion were found in islet of diabetic mice, which could be ameliorated after intervention with key receptors and kinases.

Direct inhibition of MLL-fusion proteins is a potential therapeutic strategy.

MLL-fusion depletion screen identified disulfiram for its ability to ablate MLL-fusion protein and block-associated leukaemic phenotype.

Disulfiram directly targets the CXXC domain that is essential for all MLL-fusion proteins.

Disulfiram prevents the binding to the target genes of the MLL-fusion resulting in rapid decrease in H3K27ac levels.