In the challenging tumor microenvironment (TME), tumors coexist with diverse stromal cell types. During tumor progression and metastasis, a reciprocal interaction occurs between cancer cells and their environment. These interactions involve ongoing and evolving paracrine and proximal signaling. Intrinsic signal transduction in tumors drives processes such as malignant transformation, epithelial-mesenchymal transition, immune evasion, and tumor cell metastasis. In addition, cancer cells embedded in the tumor microenvironment undergo metabolic reprogramming. Their metabolites, serving as signaling molecules, engage in metabolic communication with diverse matrix components. These metabolites act as direct regulators of carcinogenic pathways, thereby activating signaling cascades that contribute to cancer progression. Hence, gaining insights into the intrinsic signal transduction of tumors and the signaling communication between tumor cells and various matrix components within the tumor microenvironment may reveal novel therapeutic targets. In this review, we initially examine the development of the tumor microenvironment. Subsequently, we delineate the oncogenic signaling pathways within tumor cells and elucidate the reciprocal communication between these pathways and the tumor microenvironment. Finally, we give an overview of the effect of signal transduction within the tumor microenvironment on tumor metabolism and tumor immunity.

Electrochemical CO₂ reduction (CO₂RR) to produce high value-added chemicals or fuels is a promising technology to address the greenhouse effect and energy challenges. Formate is a desirable product of CO₂RR with great economic value. Here, nitrogen-doped bismuth nanosheets (N-BiNSs) were prepared by a facile one-step method. The N-BiNSs were used as efficient electrocatalysts for CO₂RR with selective formate production. The N-BiNSs exhibited a high formate Faradic efficiency (FE_formate) of 95.25% at −0.95 V (vs. RHE) with a stable current density of 33.63 mA cm⁻² in 0.5 M KHCO₃. Moreover, the N-BiNSs for CO₂RR yielded a large current density (300 mA cm⁻²) for formate production in a flow-cell measurement, achieving the commercial requirement. The FE_formate of 90% can maintain stability for 14 h of electrolysis. Nitrogen doping could induce charge transfer from the N atom to the Bi atom, thus modulating the electronic structure of N-Bi nanosheets. DFT results demonstrated the N-BiNSs reduced the adsorption energy of the *OCHO intermediate and promoted the mass transfer of charges, thereby improving the CO₂RR with high FE_formate. This study provides a valuable strategy to enhance the catalytic performance of bismuth-based catalysts for CO₂RR by using a nitrogen-doping strategy.

Uremia is a serious threat to health. Infection associated with inflammation frequently occurs in patients with uremia during hemodialysis. This study aimed to investigate the association between serum inflammatory factors and uremia in patients prior to and following hemodialysis. Patients with uremia (n=200) receiving continuous high throughput hemodialysis that had hospital‑acquired infection were enrolled between August 2013 and August 2015. Additionally, 200 cases of healthy volunteers were selected as the control. Reverse transcription‑polymerase chain reaction, ELISA and western blotting were performed to determine serum C‑reactive protein (CRP), interleukin 2 (IL‑2), and tumor necrosis factorα levels (TNF‑α) prior to hemodialysis and 8 months after hemodialysis to explore the association of CRP, IL‑2 and TNF‑α with uremia. CRP, IL‑2 and TNF‑α levels were lower at 8 months after hemodialysis than before, and the difference was statistically significant. CRP, IL‑2 and TNF‑α levels in uremia patients at 8 months after hemodialysis were similar with that in the normal control. CRP expression in patients with uremia was positively correlated with IL‑2 and TNF‑α expression. Patients with uremia with hospital‑acquired infection receiving continuous high throughput blood purification presented increased levels of inflammatory factor in the serum. In conclusion, uremia patients receiving maintenance hemodialysis with hospital‑acquired infection had increased serum inflammatory factors and high throughput hemodialysis significantly decreased CRP, IL‑2 and TNF‑α levels in the serum, suggesting that high throughput hemodialysis may be beneficial for the prevention of the infections in uremia patients.

Cancer cells frequently alter their metabolism to support biogenesis and proliferation and survive specific metabolic stressors. The glucose-associated pentose phosphate pathway (PPP) is crucial for cancer cell proliferation. In particular, 6-phosphogluconate dehydrogenase (6PGD), the second dehydrogenase in the PPP, catalyzes the decarboxylation of 6-phosphogluconate into ribulose 5-phosphate (Ru5P). However, the mechanisms controlling 6PGD expression in cancer cells remain unclear. Herein, we show that TAp73 increases Ru5P and NADPH production through 6PGD activation to counteract reactive oxygen species and protects cells from apoptosis. Moreover, 6PGD overexpression rescues the proliferation and tumorigenic ability of TAp73-deficient cells. These findings further establish the critical role of TAp73 on glucose metabolism regulation, demonstrating that TAp73 can activate 6PGD expression to support oncogenic cell growth. Implications: By transcriptional upregulation of 6PGD, TAp73 promotes the generation of Ru5P and NADPH, and enhances tumor cell proliferation.