Wood waste-derived dual-mode materials paving the way for year-round energy saving in buildings.

In the face of the challenges posed by global warming, traditional methods of building heating and cooling contribute significantly to electricity and coal consumption, thereby emitting considerable amounts of greenhouse gases. Here, a dual-mode thermal management structural material is created by processing sustainable cellulose and lignin derived from wood waste into gels, followed by lamination. The cellulose surface of the material exhibits the ability to scatter solar radiation backward while emitting strongly in the mid-infrared wavelengths, whereas the lignin surface absorbs visible and near-infrared light, primarily releasing energy through non-radiative transitions. Consequently, the material can achieve sub-ambient radiative cooling of 6 °C and solar heating of 27.5 °C during the daytime by simply flipping its orientation. This pioneering material showcases the potential to significantly reduce cooling energy consumption by an average of 18% and heating energy consumption by 42%. Moreover, the integration of a thermal-electric generator within the dual-layer structure optimally utilizes the temperature differential between the two layers, converting it into electrical power. Notably, the dual-mode thermal management structural material exhibits impressive mechanical strength, boasting a flexural strength of 102 MPa, surpassing that of natural wood by over 4.8 times. With its dual-mode functionality and embedded thermal-electric generator, this material represents a crucial step towards achieving both thermal comfort and energy autonomy in sustainable building practices, thereby contributing to a more environmentally friendly and efficient future.

Advancements and Obstacles of PARP Inhibitors in Gastric Cancer.

Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC. Recent targeted sequencing studies have revealed frequent mutations in DNA damage repair (DDR) pathway genes in many GC patients. These mutations lead to an increased reliance on poly (adenosine diphosphate-ribose) polymerase (PARP) for DNA repair, making PARP inhibitors (PARPi) a promising treatment option for GC. This article presents a comprehensive overview of the rationale and development of PARPi, highlighting its progress and challenges in both preclinical and clinical research for treating GC.

Toll-like receptor 4 signaling pathway mediates both liver and kidney injuries in mice with hepatorenal syndrome.

Hepatorenal syndrome (HRS) is a complication of cirrhosis with high morbidity and mortality. Nevertheless, the underlying mechanism involving how kidney injury aggravates the progression of cirrhosis remains unclear. This study aims to explore the role of the Toll-like receptor 4 (TLR4) signaling pathway in mediating liver and kidney injuries in HRS mice induced by unilateral ureteral obstruction (UUO) and/or bile duct ligation (BDL). Two weeks after UUO, there were no obvious pathological changes in mouse liver and the unligated side of kidney. Nevertheless, impaired liver and kidney functions, inflammatory response, and fibrosis were examined in mice after 2 wk of BDL. Compared with those of other groups, mice in the BDL + UUO group presented severer liver and kidney injuries, higher levels of inflammatory factors, and faster deposition of collagens, suggesting that kidney injuries accelerated the aggravation of HRS. Correlation analysis identified a positive correlation between expression levels of inflammatory factors and fibrotic levels. Meanwhile, TLR4 and its ligand MyD88 were upregulated during the process of liver and kidney injuries in HRS mice. Further animal experiments in transgenic TLR4-/- mice or in those treated with TAK242, a small molecule inhibitor of TLR4, showed that blocking the TLR4 signaling pathway significantly improved survival quality and survival rate in HRS mice by alleviating liver fibrosis and kidney injury. It is concluded that kidney dysfunction plays an important role in the aggravation of cirrhosis, which may be attributed to the TLR4 signaling pathway. Targeting TLR4 could be a promising therapeutic strategy for protecting both liver and kidneys in patients with HRS.NEW & NOTEWORTHY Our study established BDL, UUO, and BDL + UUO models, providing a novel idea for analyzing liver and kidney diseases. It is highlighted that the kidney injury accelerated the aggravation of HRS via inflammatory response, which could be protected by inhibiting the TLR4 signaling pathway. We believed that targeting TLR4 was a promising therapeutic strategy for protecting both liver and kidney functions in patients with HRS.

Total C-21 Steroidal Glycosides From Baishouwu Ameliorate Hepatic and Renal Fibrosis by Regulating IL-1ß/MyD88 Inflammation Signaling.

Fibrosis is a worldwide public health problem, which typically results from chronic diseases and often leads to organ malfunction. Chronic inflammation has been suggested to be the major trigger for fibrogenesis, yet mechanisms by which inflammatory signals drive fibrogenesis have not been fully elucidated. Total C-21 steroidal glycosides (TCSG) from Baishouwu are the main active components of the root of Cynanchum auriculatum Royle ex Wight, which exert hepatoprotective and anti-inflammation properties. In this study, we established a mouse model with the coexistence of hepatic and renal fibrosis and aimed to investigate the effects of TCSG from Baishouwu on fibrosis and explored the potential mechanisms. The results of biochemical and pathological examinations showed that TCSG from Baishouwu improved liver and kidney function and alleviated hepatic and renal fibrosis by reducing collagen and extracellular matrix deposition in bile duct ligation and unilateral ureteral occlusion (BDL&UUO) mice. According to network pharmacology analysis, the mechanisms underlying the effects of TCSG from Baishouwu on hepatic and renal fibrosis were associated with inflammatory response pathways, including "Signaling by interleukins", "MAP kinase activation", "MyD88 cascade initiated on plasma membrane", and "Interleukin-1 family signaling". Regression analysis and western blot results revealed that IL-1ß/MyD88 inflammation signaling played an essential role in the anti-fibrotic effects of TCSG from Baishouwu. Further data displayed that TCSG from Baishouwu affected inflammatory response and extracellular matrix deposition via suppressing the activation of p38 MAPK/JNK and NF-κB p65 signaling cascades both in the liver and kidney of BDL&UUO mice. Thus, our findings suggest TCSG from Baishouwu as a natural regimen against hepatic and renal fibrosis and provide direct evidence that IL-1ß/MyD88 signaling crucially contributes to hepatic and renal fibrosis and modulates liver-kidney crosstalk by maintaining tight control over inflammatory responses.

[Effect of C21 steroidal glycoside of Cynanchum auriculatum on liver and kidney fibrosis through TLR4 pathway].

The liver and kidney fibrosis model was established by thioacetamide(TAA) and unilateral ureteral obstruction(UUO) in SD rats. The rats were randomly divided into three groups: model group, low and high-dose groups of C21 steroidal glycosides of Cynanchum auriculatum. Another blank control group was set. Four weeks later, serum was taken to detect the biochemical indexes of liver and kidney function. Urine protein and urine creatinine were detected by kits. Liver and kidney tissue samples were stained with HE and Masson staining, and hydroxyproline content was detected. Western blot was used to detect expressions of fibrotic proteins, inflammatory factors and TLR4 signaling pathways, so as to observe the preventive and therapeutic effects of C21 steroidal glycosides from C. auriculatum on hepatic and renal fibrosis and explore its molecular mechanism. Four weeks later, serum biochemical results showed that liver and kidney functions were seriously damaged, and pathological sections showed that inflammatory cell infiltration, decrease of parenchymal cells, and increase of interstitial fibrosis in liver and kidney tissues. The results showed that low and high doses(150, 300 mg·kg~(-1)) of C21 steroidal glycosides could significantly reduce the collagen deposition and the pathological changes of liver and kidney fibrosis compared with the model group. At the same time, we found that the expression levels of TLR4 and MyD88 signaling pathway proteins were significantly increased in the liver and kidney tissues of the model group, and a large number of NF-κB signaling pathway proteins migrated into the nucleus. On the contrary, the expression levels of TLR4, MyD88 signaling pathway proteins and the nuclear migration of NF-κB were significantly inhibited in the low and high dose groups of C21 steroidal glycosides from C. auriculatum. Therefore, it was speculated that the mechanism of C21 steroidal glycoside for preventive and therapeutic effect on hepatic and renal fibrosis was related to inhibit TLR4/MYD88/NF-κB inflammatory pathway, thus preventing hepatic and renal fibrosis.