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Abstract: The cool season (November–March) of 2022–2023 was exceptional in the western United States (US), with the highest precipitation totals in ≥128 years in some areas. Recent precipitation extremes and expectations based on thermodynamics motivate us to evaluate the evidence for an anthropogenic intensification of western US cool‐season precipitation to date. Over cool seasons 1951–2023, trends in precipitation totals on the wettest cool‐season days were neutral or negative across the western US, and significantly negative in northern California and parts of the Pacific Northwest, counter to the expected net intensification effect from anthropogenic forcing. Multiple reanalysis data sets indicate a corresponding lack of increase in moisture transports into the western US, suggesting that atmospheric circulation trends over the North Pacific have counteracted the increases in atmospheric moisture expected from warming alone. The lack of precipitation intensification to date is generally consistent with climate model simulations. A large ensemble of 648 simulations from 35 climate models suggests it is too soon to detect anthropogenic intensification of precipitation across much of the western US. In California, the 35‐model median time of emergence for intensification of the wettest days is 2080 under a mid‐level emissions scenario. On the other hand, observed reductions of precipitation extremes in California and the Pacific Northwest are near the lower edge of the large ensemble of simulated trends, calling into question model representation of western US precipitation variability.

Abstract: On seasonal time scales, vapor pressure deficit (VPD) is a known predictor of burned area in the southwestern United States (“the Southwest”). VPD increases with atmospheric warming due to the exponential relationship between temperature and saturation vapor pressure. Another control on VPD is specific humidity, such that increases in specific humidity can counteract temperature-driven increases in VPD. Unexpectedly, despite the increased capacity of a warmer atmosphere to hold water vapor, near-surface specific humidity decreased from 1970 to 2019 in much of the Southwest, particularly in spring, summer, and fall. Here, we identify declining near-surface humidity from 1970 to 2019 in the southwestern United States with both reanalysis and in situ station data. Focusing on the interior Southwest in the months preceding the summer forest fire season, we explain the decline in terms of changes in atmospheric circulation and moisture fluxes between the surface and the atmosphere. We find that an early spring decline in precipitation in the interior region induced a decline in soil moisture and evapotranspiration, drying the lower troposphere in summer. This prior season precipitation decline is in turn related to a trend toward a Northern Hemisphere stationary wave pattern. Finally, using fixed humidity scenarios and the observed exponential relationship between VPD and burned forest area, we estimate that with no increase in temperature at all, the humidity decline alone would still lead to nearly one-quarter of the observed VPD-induced increase in burned area over 1984–2019. Significance Statement: Burned forest area has increased significantly in the southwestern United States in recent decades, driven in part by an increase in atmospheric aridity [vapor pressure deficit (VPD)]. Increases in VPD can be caused by a combination of increasing temperature and decreasing specific humidity. As the atmosphere warms with climate change, its capacity to hold moisture increases. Despite this, there is a decrease in near-surface air humidity in the interior southwestern United States over 1970–2019, which during the summer is likely caused by a decline in early spring precipitation leading to limited soil moisture and evaporation in spring and summer. We estimate that this declining humidity alone, without an increase in temperature, would cause about one-quarter of the VPD-induced increase in burned forest area in this region over 1984–2019.

ObjectiveApplying the in vivo Mammalian Alkaline Comet Test， this study aimed to investigate the DNA damage caused by the food additive titanium dioxide and nano-titanium dioxide on rat liver cells.MethodsAccording to the guideline “In vivo mammalian alkaline comet assay” （OECD TG489）， male SD rats were randomly divided into nine groups，five rats per group. Food additive titanium dioxide was administered to three groups at doses of 1000， 500 and 250 mg/kg·BW， while pure water served as the negative control. Titanium dioxide nanoparticle was administered in three different doses： 500， 150， and 50 mg/kg·BW. The negative control group received 0.8% Tween + 3% FBS. Test substances were administered by gavage once a day for 15 d. Simultaneously， a positive control group was established， and the positive substance ethyl methyl sulfonate （EMS） was administered once daily on the 14th and 15th days via gavage， at a dosage of 200 mg/kg·BW·d. Animals were anesthetized six hours after the last administration，and the livers were harvested to prepare single-cell suspension smears. The sections were subsequently subjected to lysis，unwinding， electrophoresis， staining to acquire the comet images for analyzing.ResultsThere were no statistical differences （P>0. 05） in the percentages of tail DNA content between the treated and negative control rats. However， the percentage of tail DNA content of rat liver cells in the EMS group showed a significant difference compared to the negative control group （P

Cancer-associated fibroblasts (CAFs) play critical roles in the tumor microenvironment and exert tumor-promoting or tumor-retarding effects on cancer development. Astragaloside IV has been suggested to rescue the pathological impact of CAFs in gastric cancer. This study aimed to investigate the potential mechanism of astragaloside IV in the regulation of CAF pathological functions in gastric cancer development. Homeobox A6 (HOXA6), and Zinc Finger and BTB Domain Containing 12 (ZBTB12) are highly expressed in gastric CAFs compared with normal fibroblasts (NFs) based on the GSE62740 dataset. We found that astragaloside IV-stimulated CAFs suppressed cell growth, migration, and invasiveness of gastric cancer cells. HOXA6 and ZBTB12 were downregulated after astragaloside IV treatment in CAFs. Further analysis revealed that HOXA6 or ZBTB12 knockdown in CAFs also exerted inhibitory effects on the malignant phenotypes of gastric cells. Additionally, HOXA6 or ZBTB12 overexpression in CAFs enhanced gastric cancer cell malignancy, which was reversed after astragaloside IV treatment. Moreover, based on the hTFtarget database, ZBTB12 is a target gene that may be transcriptionally regulated by HOXA6. The binding between HOXA6 and ZBTB12 promoter in 293T cells and CAFs was further confirmed. HOXA6 silencing also induced the downregulation of ZBTB12 mRNA and protein in CAFs. Astragaloside IV was demonstrated to regulate the expression of ZBTB12 by mediating the transcriptional activity of HOXA6. Our findings shed light on the therapeutic value of astragaloside IV for gastric cancer.

We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. These data also reveal how differential glycosylation influences CSC fate.