Primary liver cancer is one of the most common and aggressive human malignancies worldwide. As numerous studies have revealed that WW domain containing E3 Ub‑protein ligase 2 (WWP2) exerts cancer‑specific functions, the present study assessed the role of WWP2 in liver cancer. WWP2 was revealed to be significantly overexpressed in liver cancer tissues compared with paired normal tissues at the mRNA as well as at the protein level. Furthermore, small interfering RNA-mediated WWP2 knockdown in liver cancer cell lines was demonstrated to inhibit cell proliferation, cause cell cycle arrested in G1 phase and to induce apoptosis as revealed by a Cell Counting Kit-8 assay and flow cytometric analysis. In addition, western blot analysis revealed that WWP2 knockdown significantly increased the expression of apoptosis-associated markers caspase‑7, caspase‑8 and B-cell lymphoma 2 (Bcl-2)-associated X in liver cancer cell lines, while Bcl‑2 was significantly decreased. In conclusion, the present study suggested that WWP2 may exert important functions in the over‑proliferation and evasion of apoptosis of liver cancer, likely through regulating the expression of apoptosis-associated markers. Furthermore, WWP2 may represent a novel diagnostic marker and molecular therapeutic target for liver cancer.

Somatostatin-positive (SOM⁺) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM⁺ interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOM^tdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOM^tdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM⁺ neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM⁺ neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM⁺ neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund’s adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aβ-eEPSCs and Aβ-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM⁺ neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM⁺ neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM⁺ neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role.

Microbial corrosion poses a significant threat to architectural heritage worldwide. This study used metagenomics to investigate microbial diversity and taxonomic groups present in the door walls of the Ji family’s residential houses, as well as their biological functions and chemical cycles. Taxonomic annotation revealed the predominant microbial taxa associated with wall corrosion, shedding light on their potential impact on structural integrity. Moreover, analyzing the metabolites and pathways present in these microbial communities allows for a thorough understanding of their functional capabilities. Our results revealed that areas with significant damage (dwelling bad door (DBD) and dwelling bad wall (DBW)) exhibited a higher microbial diversity compared to undamaged areas (dwelling good door (DGD) and dwelling good wall (DGW)), with variations in the occurrence of archaeal and bacterial species. The presence of bacteria was found to be connected with impaired function in DBW, whereas changes in the community patterns of Sphingobium and Sphingomonas, as well as a decrease in Cercospora proportion and an increase in Fusarium proportion, were correlated with damage in DBD. Both the Entner–Doudoroff (ED) route and sulfide oxidation processes were observed in both damaged locations (DBD and DBW). However, significant nitrogen-cycling mechanisms, including dissimilatory nitrate reduction to ammonium, were only found in DBW. Furthermore, DBD specifically detected the shift from methyl mercaptan (MMPA) to methyl mercaptan (MeSH). This research highlights the intricate interplay between microbial communities and the physical deterioration of residential structures, emphasizing the importance of understanding microbial ecology in mitigating such issues.

Infections caused by Gram‐negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug‐resistant bacteria. Here, we report a new approach to combat infections by targeting iron‐binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe³⁺‐(citrate)₂ complex. Based on these results, a structure‐based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.

Infections caused by Gram‐negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug‐resistant bacteria. Here, we report a new approach to combat infections by targeting iron‐binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe³⁺‐(citrate)₂ complex. Based on these results, a structure‐based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.