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Herein, we developed a synthetic strategy for the direct construction of C–S bonds to obtain biologically active sulfur-containing compounds and a methodology involving the reductive sulfuration of aldehydes or ketones to obtain diverse substituted thiol, disulfide, and thioester derivatives. EtOCS2K is demonstrated as a potential substitute for the Berzelius reagent or Lawesson's reagent for the construction of C–S bonds. [ABSTRACT FROM AUTHOR]

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract (NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive (Calb1+) NTS neurons that are molecularly distinct from Tac1+ neurons. These Calb1+ neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+ NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins. [ABSTRACT FROM AUTHOR]

Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. Thus, the immune systems of long‐lived mammals present unique models to study healthy longevity. To identify the molecular clues of anti‐immunosenescence, we first built high‐quality reference genome for a long‐lived myotis bat, and then compared three long‐lived mammals (i.e., bat, naked mole rat, and human) versus the short‐lived mammal, mouse, in splenic immune cells at single‐cell resolution. A close relationship between B:T cell ratio and immunosenescence was detected, as B:T cell ratio was much higher in mouse than long‐lived mammals and significantly increased during aging. Importantly, we identified several iron‐related genes that could resist immunosenescence changes, especially the iron chaperon, PCBP1, which was upregulated in long‐lived mammals but dramatically downregulated during aging in all splenic immune cell types. Supportively, immune cells of mouse spleens contained more free iron than those of bat spleens, suggesting higher level of ROS‐induced damage in mouse. PCBP1 downregulation during aging was also detected in hepatic but not pulmonary immune cells, which is consistent with the crucial roles of spleen and liver in organismal iron recycling. Furthermore, PCBP1 perturbation in immune cell lines would result in cellular iron dyshomeostasis and senescence. Finally, we identified two transcription factors that could regulate PCBP1 during aging. Together, our findings highlight the importance of iron homeostasis in splenic anti‐immunosenescence, and provide unique insight for improving human healthspan. [ABSTRACT FROM AUTHOR]

Whether conifers can withstand environmental changes especially temperature fluctuations has been controversial. Epigenetic analysis may provide new perspectives for solving the issue. Pseudotaxus chienii is an endangered gymnosperm species endemic to China. In this study, we have examined the genetic and epigenetic variations in its natural populations aiming to disentangle the synergistic effects of climate and soil on its population (epi)genetic differentiation by using amplified fragment length polymorphism (AFLP) and methylation‐sensitive AFLP (MSAP) techniques. We identified 23 AFLP and 26, 7, and 5 MSAP outliers in P. chienii. Twenty‐one of the putative adaptive AFLP loci were found associated with climate and/or soil variables including precipitation, temperature, K, Fe, Zn, and Cu, whereas 21, 7, and 4 MSAP outliers were significantly related to precipitation of wettest month (Bio13), precipitation driest of month (Bio14), percent tree cover (PTC), and soil Fe, Mn, and Cu compositions. Total precipitation and precipitation in the driest seasons were the most influential factors for genetic and epigenetic variation, respectively. In addition, a high full‐methylation level and a strong correlation between genetic and epigenetic variation were detected in P. chienii. Climate is found of greater importance than soil in shaping adaptive (epi)genetic differentiation, and the synergistic effects of climate and climate–soil variables were also observed. The identified climate and soil variables should be considered when applying ex situ conservation. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate and analyze the effect of different application sequences of CO2 fractional laser and triamcinolone acetonide injection on the application effect of hypertrophic scar in one operation. Patients with hypertrophic scars who received CO2 lattice laser combined with triamcinolone acetonide injection from January 2021 to December 2022 were retrospectively analyzed. According to the different initial operations, they were divided into CO2 FL-TA group and TA-CO2 FL group. The Vancouver Scar Scale score and scar thickness of the two groups before and after treatment were analyzed. The complications occurred in the two groups during the treatment period. The clinical efficacy of the two groups before and after the treatment was calculated. Before treatment, there was no difference in scar thickness and VSS score between the two groups (P > 0.05). After treatment, the above indexes in CO2 FL-TA group were significantly better than those in TA-CO2 FL group (P < 0.05); the incidence of adverse reactions in CO2 FL-TA group was 9.38%, which was significantly lower than that in TA-CO2 FL group (18.75%) (P < 0.05); the total effective rate of CO2 FL-TA group was 90.63%, which was significantly higher than that in TA-CO2 FL group (65.63%) (P < 0.05). In the process of combined CO2 fractional laser and triamcinolone acetonide injection in the treatment of hypertrophic scars, CO2 fractional laser treatment first, and then triamcinolone acetonide injection can reduce the number of treatments, reduce the incidence of adverse reactions, and achieve more satisfactory treatment effect. [ABSTRACT FROM AUTHOR]

Angelica sinensis (Oliv.) Diels (Umbelliferae) is a well-known medicinal plant mainly distributed in Gansu Province of China. Its local and global demand is significant because of its food and medicinal applications. However, the early bolting rate of Angelica sinensis (Oliv.) Diels reaches 20%-60%, which seriously affects its food and medicinal qualities. Thus, differences in gene expression between the flower bud and sprout-shoot apical meristem underwent analysis, by means of cDNA-amplified restriction fragment length polymorphism, to better understand the flowering mechanism. 64 primer sets, each of which amplified to 60 transcript-derived fragments (TDFs), were used. Among these TDFs, 26 were expressed specifically in the flower bud. After cloning and sequencing, 32 distinct sequences were obtained from these 26 TDFs, and 25 were found with homologous sequences in databases. Confirmation of differential expression of 13 sequences was obtained by semi-quantitative RT-PCR, their showing higher expression levels in flower buds. These homologous sequences encode transposable elements, pentatricopeptide repeat-containing proteins, DNA-binding transcription factors, zinc finger (B-box type) family proteins, NADP-dependent sorbitol 6-phosphate dehydrogenase (S6PDH), amongst others.

The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor β (TGF-β), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-β. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation., Competing Interests: Declaration of interests C.S. and G.C. filed a patent application based on early lineage-specific differentiation and cardiomyocyte differentiation that is induced by ERK5 inhibitor., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of sodium bicarbonated Ringer's solution (BRS) on lactate metabolism, acid-base balance, and clinical outcomes in elderly patients undergoing gastrointestinal surgery., Methods: A total of 60 elderly patients undergoing gastrointestinal surgery were enrolled in this prospective, randomized controlled study. The participants were randomly assigned to the BRS group (n = 30) or sodium lactated Ringer's solution (LRS) group (n = 30) where they received goal-directed fluid therapy with BRS or LRS, respectively. The primary outcome was the incidence of postoperative hyperlactatemia, whereas the secondary outcomes included pH, bicarbonate, base excess (BE), liver function, and postoperative complications within 30 days. Linear regression was conducted to screen the factors affecting lactate concentration., Results: After fluid therapy, the probability of hyperlactatemia was lower in the BRS group than in the LRS group (3.3% vs. 40.0%, P < 0.001). No significant difference in bicarbonate, pH, and BE was observed between the groups ( P > 0.05). Furthermore, the incidence of major complications and the length of hospital stay were not significantly different ( P > 0.05). However, the BRS group had a lower risk of minor complications than the LRS group (50.0% vs. 76.7%, P = 0.032), particularly in terms of impaired liver function (16.7% vs. 43.3%, P = 0.024). Diabetes, hypotension, and volume of LRS infused were highly correlated with lactate concentration., Conclusion: BRS is more beneficial to the reduction of the incidence of postoperative hyperlactatemia and the risk of minor postoperative complications in elderly patients undergoing gastrointestinal surgery. Therefore, BRS may be a better option for perioperative fluid therapy in elderly patients undergoing gastrointestinal surgery., Competing Interests: None., (AJTR Copyright © 2023.)

Objective: This study aimed to compare the ability of three frailty assessments to predict adverse outcomes after elective gastrointestinal surgery and analyze how frailty assessments impact the American Society of Anesthesiologists (ASA) risk prediction model., Methods: Frailty was measured using the FRAIL scale, Fried Phenotype (FP), and Clinical Frailty Scale (CFS), alongside ASA assessments before surgery. Univariate and logistic regression analyses were used to determine the predictive value of each method. The predictive abilities of the tools were assessed by the area under the receiver operating characteristic curves (AUCs) and their 95% confidence intervals (CIs)., Results: After adjusting for age and other risk factors, logistic regression analysis revealed significant positive associations between preoperative frailty and postoperative total adverse systemic complications (odds ratios [ORs] [95% CIs]: FRAIL, 1.297 [0.943-1.785]; FP, 1.317 [0.965-1.798]; CFS, 2.046 [1.413-3.015]; P < 0.001). The CFS was the best predictor of any adverse systemic complications (AUC, 0.696; 95% CI, 0.640-0.748). The predictive abilities of the FRAIL scale (AUC, 0.613; 95% CI, 0.555-0.669) and FP (AUC, 0.615; 95% CI, 0.557-0.671) were similar. The CFS and ASA assessment combined (AUC, 0.697; 95% CI, 0.641-0.749) had a statistically improved AUC compared to the ASA assessment alone (AUC, 0.636; 95% CI, 0.578-0.691), illustrating their value for predicting any adverse systemic complications., Conclusion: Frailty instruments enhance the accuracy of predicting postoperative outcome in older adults. Clinicians should add frailty assessments before preoperative ASA, particularly the CFS, given its ease of use and clinical feasibility., Competing Interests: None., (AJTR Copyright © 2023.)