Photocatalyzed C3-H Nitrosylation of Imidazo[1,2-a]pyridine under Continuous Flow and External Photocatalyst-, Oxidant-, and Additive-Free Conditions.

This study reports a protocol for the highly regioselective photocatalyzed C-H nitrosylation of imidazo[1,2-a]pyridine scaffolds at the C3 position under a combination of visible-light irradiation and continuous flow without any external photocatalyst. This protocol involves mild and safe conditions and shows good tolerance to air and water along with excellent functional group compatibility and site selectivity, generating various 3-nitrosoimidazo[1,2-a]pyridines in excellent yields under photocatalyst-, oxidant-, and additive-free conditions.Notably, the proposed nitrosylation reaction, which introduces the chromophore NO into imidazo[1,2-a]pyridine scaffolds, occurs efficiently under visible-light irradiation without any additional photocatalyst owing to the intense light-absorption characteristics of the nitrosylation products. This study could guide future studies on the development of green organic-synthesis strategies with a wide variety of potential applications.

The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells.

Abnormal ovarian function is the main manifestation of female reproductive toxicity. Granulosa cells (GCs) play an important role in determining the fate of follicles and are the main effector cells of the female reproductive system. Excessive apoptosis of GCs leads to pathological folliculogenesis and further reproductive damage. However, drugs available for treatment of female reproductive toxicity are limited. Recent studies have confirmed that various natural products and bioactive ingredients of traditional Chinese medicine (TCM) can inhibit apoptosis of GCs and protect ovarian function. In this review, the mechanisms underlying the proapoptotic and antiapoptotic effects of natural products and bioactive ingredients of TCM on the proliferation, function, and apoptosis of GCs are summarized based on the findings of reports published over the past 10 years as reference for the treatment of female reproductive toxicity.

Protocatechuic Acid Alleviates Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Mice via the Regulation of Intestinal Flora and Ferroptosis.

Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.

Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules.

Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle.

[Assessment of the lagging effect of vegetation response and loss probability in the Pearl River basin under drought stress]. / å¹²æ—±èƒè¿«ä¸‹ç æ±ŸæµåŸŸæ¤è¢«å“åº”çš„æ»žåŽæ•ˆåº”åŠæŸå¤±æ¦‚çŽ‡è¯„ä¼°.

We quantified the lag time of vegetation response to drought in the Pearl River basin (PRB) based on the standardized precipitation evapotranspiration index (SPEI) and normalized difference vegetation index (NDVI), and constructed a vegetation loss probability model under drought stress based on the Bayesian theory and two-dimensional joint distribution. We further quantitatively evaluated the spatial variations of loss probability of four vegetation types (evergreen broadleaf forest, mixed forest, grassland, and cropland) under different drought intensities. The results showed that the drought risk in eastern West River, the upper reaches of North River and East River, and southern Pearl River Delta was obviously higher than that in other regions during 1982-2020. The response time of vegetation to drought in high-altitude areas in the upper reaches of PRB (mostly<3 month) was generally shorter than that in low altitude areas (>8 month). Drought exacerbated the probability of vegetation loss, with higher vulnerability of mixed forest than the other three vegetation types. The loss probability of vegetation was lower in northwestern PRB than that in central PRB.

Anthropogenic climate change exacerbates the risk of successive flood-heat extremes: Multi-model global projections based on the Inter-Sectoral Impact Model Intercomparison Project.

The successive flood-heat extreme (SFHE) event, which threatens the securities of human health, economy, and building environment, has attracted extensive research attention recently. However, the potential changes in SFHE characteristics and the global population exposure to SFHE under anthropogenic warming remain unclear. Here, we present a global-scale evaluation of the projected changes and uncertainties in SFHE characteristics (frequency, intensity, duration, land exposure) and population exposure under the Representative Concentration Pathway (RCP) 2.6 and 6.0 scenarios, based on the multi-model ensembles (five global water models forced by four global climate models) within the Inter-Sectoral Impact Model Intercomparison Project 2b framework. The results reveal that, relative to the 1970-1999 baseline period, the SFHE frequency is projected to increase nearly globally by the end of this century, especially in the Qinghai-Tibet Plateau (>20 events/30-year) and the tropical regions (e.g., northern South America, central Africa, and southeastern Asia, >15 events/30-year). The projected higher SFHE frequency is generally accompanied by a larger model uncertainty. By the end of this century, the SFHE land exposure is expected to increase by 12 % (20 %) under RCP2.6 (RCP6.0), and the intervals between flood and heatwave in SFHE tend to decrease by up to 3 days under both RCPs, implying the more intermittent SFHE occurrence under future warming. The SFHE events will lead to the higher population exposure in the Indian Peninsula and central Africa (<10 million person-days) and eastern Asia (<5 million person-days) due to the higher population density and the longer SFHE duration. Partial correlation analysis indicates that the contribution of flood to the SFHE frequency is greater than that of heatwave for most global regions, but the SFHE frequency is dominated by the heatwave in northern North America and northern Asia.

Shaoyao Gancao Decoction protects against dextran sulfate sodium-induced ulcerative colitis by down-regulating ferroptosis.

OBJECTIVES: Shaoyao Gancao Decoction (SGD) is a well-known Chinese herbal prescription used to treat ulcerative colitis (UC). This study was designed to evaluate the effect of SGD in dextran sulfate sodium-induced UC and to reveal the potential mechanism. METHODS: A UC mouse model was established by the administration of dextran sulfate sodium. The mice were given SGD extract intragastrically for 7 days. Histological pathology, inflammatory factors, and ferroptosis regulators were determined in vivo. In addition, ferroptotic Caco-2 cells were prepared to investigate the underlying mechanism of the effects of SGD. KEY FINDINGS: The results showed that SGD reduced the disease activity index, the level of inflammatory factors, and histological damage in mice with UC. Moreover, SGD down-regulated the level of ferroptosis in cells in colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production, compared with the model group. Correspondingly, similar effects of SGD on ferroptosis were observed in Erastin-treated Caco-2 cells. The results of our in vitro reactive oxygen species assays and the changes in mitochondrial structure observed by scanning electron microscopy also supported these results. CONCLUSION: Taken together, these findings suggest that SGD protected against UC by down-regulating ferroptosis in colonic tissue.

Can Priming Legal Consequences and the Concept of Honesty Decrease Cheating During Examinations?

Cheating on exams is a very common phenomenon that causes great harm. Various measures, such as chastisement and direct punishment, have been employed to reduce cheating. Previous studies have found that increasing punishment and activating "self-concept maintenance" can reduce this behavior. This study employed a priming paradigm to investigate whether priming legal consequences and the concept of honesty would reduce cheating in examination situations. In experiment 1, a total of 402 freshmen from 17 classes were included in this study. The 185 students in experimental condition were primed for legal consequences. The cheating behaviors and employed analysts were defined to count the number of cheaters. The results show that the number of students cheating in the primed group did not decrease compared to those in the controlled condition. In experiment 2, a total of 386 freshmen from 16 classes participated in this experiment. The 171 students in experimental condition were primed for the concept of honesty. The results also show that the number of students cheating in the primed group did not decrease. This study shows that priming legal consequence and the concept of honesty were not significant in certain situations, such as during examinations. It is suggested that some psychological manipulations in decreasing dishonesty behaviors should be further tested in ecological situations.