Periploca forrestii

Periploca forrestii Schltr. has been used as a Chinese folk medicine due to its versatile pharmacological effects such as promoting wounds and rheumatoid arthritis. However, the antiarthritic activity of Periploca forrestii saponin (PFS) and its active compound Periplocin has still not been demonstrated. Here, we evaluated the antiarthritic effects of PFS in adjuvant-induced arthritis (AIA) rats by intragastric administration at a dose of 50 mg/kg. The anti-inflammatory activities of Periplocin were also examined in LPS-induced AIA splenocytes and synoviocytes. PFS significantly ameliorated joint swelling; inhibited bone erosion in joints; lowered levels of IL-6 and TGF-β1 in AIA rat splenocyte; and reduced joint protein expression levels of phospho-STAT3 and IKKα. Using LPS-induced AIA splenocytes, we demonstrate that Periplocin suppressed the key proinflammatory cytokines levels of IL-6, IFN-γ, TGF-β1, and IL-13 and IL-22 and transcription factor levels of T-bet, GATA3, and C-Jun genes. Periplocin also suppressed LPS-induced cytokine secretion from synoviocytes. Our study highlights the antiarthritic activity of PFS and its derived Periplocin and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of Periploca forrestii Schltr. as an alternative modality for the treatment of RA

PGE 2

In the current study, we investigated the effect of a long-acting β-agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10(−7) and 10(−6) M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10(−5) M). In the presence of 10(−8) M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10(−7) ~10(−5) M). Blockade of endogenous PGE(2) by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. Pretreatment with PGE(2) abolished the inhibitory effect of salmeterol, but it potentiated the inhibitory effect of cilomilast on fibroblast-mediated collagen gel contraction. Finally, indomethacin slightly inhibited PDE4C expression, while PGE(2) stimulated the expression of PDE4A and -4C in human lung fibroblasts. These findings suggest that long-acting β-agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and that PGE(2) can modulate the effect of β-agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression

Improvement on the Linearity Response of PandaX-4T with new Photomultiplier Tubes Bases

With the expanding reach of physics, xenon-based detectors such as PandaX-4T in the China Jinping Underground Laboratory aim to cover an energy range from sub-keV to multi-MeV. A linear response of the photomultiplier tubes (PMTs) is required for both scintillation and electroluminescence signals. Through a dedicated bench test, we investigated the cause of the non-linear response in the Hamamatsu R11410-23 PMTs used in PandaX-4T. The saturation and suppression of the PMT waveform observed during the commissioning of PandaX-4T were caused by the high-voltage divider base. The bench test data validated the de-saturation algorithm used in the PandaX-4T data analysis. We also confirmed the improvement in linearity of a new PMT base design, which will be used to upgrade the PMT readout system in PandaX-4T.Comment: 13 pages, 9 figure

TGF-β1 and serum both stimulate contraction but differentially affect apoptosis in 3D collagen gels

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-β1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-β1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-β1 and serum significantly augmented collagen gel contraction. TGF-β1 also increased apoptosis assessed by TUNEL positivity and DNA content analysis. In contrast, serum did not affect apoptosis. TGF-β1 induction of apoptosis was associated with augmented expression of Bax, a pro-apoptotic member of the Bax/Bcl-2 family, inhibition of Bcl-2, an anti-apoptotic member of the same family, and inhibition of both cIAP-1 and XIAP, two inhibitors of the caspase cascade. Serum was associated with an increase in cIAP-1 and Bcl-2, anti-apoptotic proteins. Interestingly, serum was also associated with an apparent increase in Bax, a pro-apoptotic protein. Blockade of Smad3 with either siRNA or by using murine fibroblasts deficient in Smad3 resulted in a lack of TGF-β induction of augmented contraction and apoptosis. Contraction induced by different factors, therefore, may be differentially associated with apoptosis, which may be related to the persistence or resolution of the fibroblasts that accumulate following injury

Water hazards: drought and flood

Droughts and floods are the main threats to the Lancang-Mekong River Basin (LMRB). Drought mainly occurs during the dry season, especially in March and April, in the LMRB. The “dry gets drier” paradigm performs well in the LMRB, specifically in the Mekong Delta. Further, flood frequency and magnitude, which are determined by heavy rain, are also increasing in the LMRB. Droughts and floods show obvious seasonal and regional characteristics in the LMRB. The LMRB is a well-known rainstorm-flood basin. Floods in the LMRB are mainly caused by heavy rain. The LMRB is dominated by regional floods, and basin-wide floods rarely occur. From upstream to downstream, the flood peak and flood volume have shown increasing trends. Meanwhile, moving further downstream, the flood season ends later. In the upstream areas, floods are mainly concentrated in the period from July to October, with the highest probability of floods occurring in August. For the downstream areas, the flood season is from August to October. Climate change is one of the major factors affecting the LMRB’s droughts and floods. Global warming is an indisputable fact. Under global warming, extreme hydrological events show a tendency to increase. Climate models have suggested a future potential for increased flood frequency, magnitude, and inundation in the LMRB by 10–140%, 5–44% and 19–43%, respectively. Although the severity and duration of droughts are also increasing, the differences in drought indicators projected by different climate models are significant. Hydropower development was another major factor affecting droughts and floods in the LMRB. Large-scale hydropower development has drastically changed streamflow characteristics since 2009, causing increased dry season flow (+150%) and decreased wet season flow (−25%), as well as reduced flood magnitude (−2.3  to  −29.7%) and frequency (−8.2 to −74.1%). Large-scale reservoirs will have a profound impact on hydrological characteristics, droughts and floods, agriculture, fisheries, energy supply, and environmental protection in the LMRB. Coupling climate models and hydrological models is the main way to study the impact of climate change and reservoir operation in the LMRB. Climate change indirectly affects hydrological characteristics by affecting meteorological parameters, while reservoirs can directly change the propagation from meteorological extreme events to hydrological extreme events by releasing/storing water in different situations. Hydrological models are the link connecting and quantifying the coupled effects of climate change and reservoirs. More studies are needed to develop a comprehensive understanding of the future impacts of climate change and reservoir operation on extreme events in the LMRB, as well as adaptation and mitigation measures