Kallikreins (KLKs) and metallothioneins (MTs) mRNA are increased in vaginal fluid in gestational week 18-20 in women who subsequently deliver preterm. MTs are activated in response to cytokine-mediated inflammation and oxidative stress (1). MTs regulate metalloproteinases which degrades the extracellular matrix and have been associated with preterm prelabour rupture of foetal membranes (PPROM) (2). KLKs can be mechanistically involved in preterm delivery via degradation of the cervical mucus barrier (3), modulation of anti-microbial peptides (4) and preterm prelabour rupture of foetal membranes (PPROM) (5).

1. b-AP15, an inhibitor of proteasomal deubiquitinases USP14 and UCHL5, induces cell apoptosis and downregulates BCR-ABL signaling in BCR-ABL^WT and BCR-ABL^T315I CML cell lines and primary CML cells.
2. Silencing of USP14 and UCHL5 suppresses cell proliferation and decreases BCR-ABL expression in CML cells.
3. USP14 and UCHL5 are potential targets for combating T315I mutant-triggered TKI resistance in CML.

• Severe COVID-19 patients displayed rapid extrafollicular (aN and dnCS) B cell activation.
• Mild patients engaged mitochondrial dysfunction (MD) to suppress excessive extrafollicular responses.
• Intracellular calcium drives MD, leading to the suppression of B cell response.
• Low MD in B cells correlates with higher amounts of antibodies, inflammation and severe COVID-19.

• – Traditional immunosuppression with tacrolimus and mycophenolate mofetil did not sustain human neural stem cell xenograft survival in mouse brain for more than 2 weeks.
• – Immunosuppression with monoclonal antibodies targeting CD4 and CD40L enabled long-term persistence of human stem cell transplants.
• – Transplants survive past 28 weeks in C57BL/6 mice and the 5XFAD animal model of Alzheimer's disease.

1. A series of advanced maternal age (AMA)-related changes are identified in the parental and offspring's DNA methylome, as well as the maternal and offspring's transcriptome.
2. Specific DNA methylome and transcriptional changes present intergenerationally correlation.
3. Part of the AMA-related differentially expressed genes shared by mother and offspring groups, such as HTRA3, were already significantly changed in MII oocyte or blastocyst.

• Hepatic innate immune receptor controls whole body insulin sensitivity
• Intrahepatic and extrahepatic inflammation in a murine model of NAFLD is dampened following deletion of IL-1R1 in hepatocytes
• IL-1R1 controls lipid metabolism in the liver

1. The vaccine SCoK is well tolerated in both younger adults and older adults.

2. The vaccine showed good immunogenicity and broad neutralizing capabilities.

3. A vaccine administered using 40 μg antigen at a three-dose schedule will undergo an efficacy evaluation in the phase 3 trial.

The positive regulatory loop of TCF4N/p65 promotes glioblastoma (GBM) tumourigenesis and chemosensitivity: TCF4N upregulates NF-κB activity by binding and promoting p65 S536 phosphorylation, nuclear-translocation and stability; p65 promotes alternative splicing of TCF7L2 pre-mRNA, resulting in an increase of TCF4N.

• A new 120 nt microRNA inhibitor therapeutic is specific, stable, efficient and non-toxic to cells
• Injection of the inhibitor into growing colorectal tumors inhibits and reduces tumor growth.
• miR-210 inhibition activates apoptosis, XIST and NME1 to reduce tumor growth
• This approach highlights the therapeutic application of the plasmid-based microRNA inhibition system (PMIS) for treating tumors.

• NAT10 is highly expressed in approximately 92% of cancer and it is related to cancer cell survival.
• NAT10 regulates fatty acid metabolism through ac4C-mediated mRNA stability of ELOVL6, ACSL1, ACSL3, ACSL4, ACADSB and ACAT1.
• Targeting NAT10 could be beneficial for treating severe cancer cases driven by fatty acid metabolism.

• NSUN2 expression is upregulated in PCa and associated with a worse prognosis.
• AR mRNA is modified by NSUN2 and is stabilized in an m5C-YBX1-dependent manner.
• The m5C modification located in the 5′ region of AR mRNA, influenced several AR variants including AR-V7.
• NSUN2 expression is also transcriptionally regulated by AR and can respond to ADT and ARSI treatment.

• In human HCC, S1P lyase (SPL) levels were specifically and positively linked with levels of glycerophospholipids, including lysophosphatidylinositol (LPI).
• SPL facilitates cancer progression in both a GPR55 (LPI receptor)-dependent and GPR55-independent manner.
• The novel metabolic pathway, in which SPL converts sphingolipids to glycerophospholipids, might be a novel pharmacologic target for the cancer treatment.

1. The first mass spectrometry–based proteomic analysis on small-cell lung cancer (SCLC) cell lines, reporting unique proteomic profiles of its proposed molecular subtypes.
2. SCLC subgroups detected by proteomics are consistent with mRNA-based subtypes.
3. Unique proteomic profiles of SCLC subtypes highlight potential subtype-specific therapeutic vulnerabilities and diagnostic biomarkers.

1. CD44v6 is an ideal antigen of CAR-T therapy for AML with FLT3 or DNMT3A mutations.
2. CD44v6 CAR-T cells displayed strong anti-leukemic effects and safety in vitro and in vivo.
3. FLT3 or DNMT3A mutations induced CD44v6 overexpression by downregulating the methylation of CD44 promoter.