Acid-Promoted Amination of Cyclohexenone for the Divergent Synthesis of p-Aminophenols and Tertiary Amines.

A tunable method for the selective preparation of p-aminophenol and tertiary amines from a secondary amine and cyclohexenone has been described. Nonaromatic cyclohexenones were used as an aryl source. The desired tertiary amine products were generated when using I2 as the catalyst. This approach yields single-site-selective p-aminophenol without using I2, and the 18O labeling experiments demonstrated that hydroxyl oxygen originates from O2.

Altered executive control network and default model network topology are linked to acute electronic cigarette use: A resting-state fNIRS study.

In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance. Although previous research has explored the acute effects of combustible cigarettes or nicotine replacement therapy on brain functional activities, studies on e-cigs have been limited. Using fNIRS, we conducted graph theory analysis on the resting-state functional connectivity of 61 male abstinent smokers both before and after vaping e-cigs. And we performed Pearson correlation analysis to investigate the relationship between alterations in network metrics and changes in craving. E-cig use resulted in increased degree centrality, nodal efficiency, and local efficiency within the executive control network (ECN), while causing a decrease in these properties within the default model network (DMN). These alterations were found to be correlated with reductions in craving, indicating a relationship between differing network topologies in the ECN and DMN and decreased craving. These findings suggest that the impact of e-cig usage on network topologies observed in male smokers resembles the effects observed with traditional cigarettes and other forms of nicotine delivery, providing valuable insights into their addictive potential and effectiveness as aids for smoking cessation.

Moderate to severe anemia at admission increases the risk of complications in patients over 60 years with hip fracture.

BACKGROUND: Anemia frequently occurs in patients with hip fractures and represents a risk factor that can potentially be altered. To evaluate the association between admission anemia and complications in older hip fracture patients while exploring the potential impact of anemia on complications from the perspective of overall, operation and non-operation. METHODS: This retrospective study enrolled in-patients over 60 years old with hip fractures from January 2020 to November 2023. At admission, anemic patients were identified as having a hemoglobin level below 12 g/dL in females and 13 g/dL in males. Anemia was further classified as mild, moderate, or severe. Data encompassing demographics, comorbidities, medications, information on fracture and surgery, and complications were collected. RESULTS: A total of 462/679 patients had anemia, including 348, 105, and 9 with mild, moderate, and severe anemia, respectively. A total of 281 individuals experienced complications, including 212 and 69 with and without operation, respectively. Multivariate regression analysis identified anemia as a greater risk for acute heart failure (OR = 2.056, p = 0.037, 95% CI 1.043-4.052) than non-anemia. Moderate to severe anemia was a significant risk factor for any complication (OR = 1.584, p = 0.028, 95% CI 1.050-2.390), ≥ 2 (OR = 2.364, p = 0.001, 95% CI 1.443-3.872) or 3 (OR = 2.311, p = 0.022, 95% CI 1.131-4.720) complications, delirium (OR = 2.301, p = 0.018, 95% CI 1.156-4.579), venous thromboembolism (OR = 2.031, p = 0.042, 95% CI 1.025-4.025), and acute heart failure (OR = 2.095, p = 0.016, 95% CI 1.145-3.834), compared with mild to non-anemia. Similar results were observed in operated patients, while anemia and its severity were not associated with complications in non-operated patients. CONCLUSION: Moderate to severe anemia caused complications in elderly hip fracture patients, but it was not observed in non-operated individuals. These findings would support orthopedic physicians' hierarchical management of anemic patients.

A case of neonatal tsutsugamushi disease diagnosed with the aid of rickettsial macrogenomic detection.

BACKGROUND: Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). CASE PRESENTATION: Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. CONCLUSION: Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. SUITABLE FOR PEOPLE WITH: Infectious Diseases; Neonatology; Obstetrics.

Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure.

The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.

Metal- and Solvent-Free Synthesis of Substituted Pyrimidines via an NH4I-Promoted Three-Component Tandem Reaction.

A facile and practical approach for the preparation of substituted pyrimidines from ketones, NH4OAc, and N,N-dimethylformamide dimethyl acetal has been described. This NH4I-promoted three-component tandem reaction affords a broad range of substituted pyrimidines in acceptable yields under metal- and solvent-free conditions. The present methodology features the advantages of simple and easily available starting materials, metal- and solvent-free conditions, a broad substrate scope with good functional group tolerance, and gram-scale synthesis.

Three-component selective synthesis of phenothiazines and bis-phenothiazines under metal-free conditions.

An iodine-containing reagent promoted three-component method for the selective synthesis of phenothiazines and bis-phenothiazines has been developed. The present protocol starts from simple and easily available cyclohexanones, elemental sulfur, and inorganic ammonium salts, selectively producing phenothiazines and bis-phenothiazines in satisfactory yields under aerobic conditions. This method has the advantages of simple and readily available starting materials and metal-free conditions, affording a facile and practical approach for the preparation of phenothiazines and bis-phenothiazines.

Brønsted Acid Promoted Facile Synthesis of Benzoacridines from Aromatic Aldehydes and N-Phenyl Naphthylamines.

A facile method for the rapid synthesis of benzoacridines has been described. This protocol promoted by p-toluenesulfonic acid starts from aromatic aldehydes and N-phenyl naphthylamines, affording a variety of benzoacridines in 30-90 % yields under metal-free conditions. The present approach involves a cascade of condensation, Friedel-Crafts alkylation, annulation and dehydroaromatization in one pot.

Metal- and Solvent-Free Synthesis of Tetrahydrobenzo[c]carbazolones through NaI-Catalyzed Formal [4 + 2] Annulation.

A novel strategy for the preparation of functional carbazoles through NaI-catalyzed formal [4 + 2] annulation of 2-(indol-3-yl)cyclohexanones and alkynes/alkenes has been developed. The present approach started from easily available raw materials and provided a variety of tetrahydrobenzo[c]carbazolones in satisfactory yields under metal- and solvent-free conditions. Furthermore, the products could be further transformed into structurally valuable carbazole-based conjugated derivatives.

A Mild Two-Step Synthesis of Structurally Valuable Indole-Fused Derivatives.

A mild two-step synthetic approach for the preparation of structurally valuable indolo[3',2':4,5]pyrrolo[3,2,1-kl]phenothiazines has been developed. In this work, cyclohexanone was used as the key bridge to connect the indole and phenothiazine frameworks to construct a structurally valuable indole-fused derivative. The present protocol achieved the cascade construction of multiple C-hetero bonds, affording a convenient approach access to hexacyclic-fused system that contained both indole and phenothiazine, two privileged skeletons.

Psychological Distress Reported by Primary Care Physicians in China During the COVID-19 Pandemic.

OBJECTIVE: Primary care physicians (PCPs) play a key role in responding to the COVID-19 epidemic. The objective of this study was to explore the influencing factors associated with self-reported psychological distress among a sample of PCPs in China in relation to COVID-19. METHODS: An online survey was distributed to a sample of PCPs in Chengdu city between February 10 and February 13, 2020. The survey consisted of three sections: demographic characteristics, COVID-19-related questions, and the General Health Questionnaire-12 (GHQ-12). After 5 months, a follow-up survey investigating the change of the GHQ-12 was conducted. RESULTS: A total of 712 PCPs completed the baseline survey (11.8% of those invited), 55.6% were female and 74.4% were aged between 30 and 49 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 29.2% and were associated with low preparedness, high work impact, working with infected residents, personal life impact, and concerns, as well as older age and being married (p values < .05). Logistic regression analysis showed that psychological distress was associated with low preparedness (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.87-0.96), high work impact (OR = 1.11, 95% CI = 1.03-1.20), personal life impact (OR = 1.12, 95% CI = 1.07-1.17), and safety-related concerns (OR = 1.09, 95% CI = 1.02-1.16). At the 5-month assessment point, high psychological distress was less frequent (21.8%). CONCLUSIONS: COVID-19 has resulted in high levels of distress in approximately 30% of PCPs in China. Factors associated with high psychological distress levels include low preparedness and high levels of work impact, personal life impact, and concerns. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.

Three-Component Synthesis of Dibenzoxazepinamines and Dibenzothiazepinamines under Transition-Metal-Free Conditions.

A convenient and efficient strategy for the synthesis of dibenzoxazepinamines and dibenzothiazepinamines has been developed. This three-component approach started from 2-nitrobenzaldehydes, 2-aminophenols, and methoxyammonium chlorides under metal-free conditions. The protocol has the advantages of readily available starting materials, simple and facile conditions, gram-scale synthesis, and broad substrate scope, providing an efficient and practical strategy for the preparation of potential drug-active dibenzoxazepinamines and dibenzothiazepinamines in one pot.

Acid-catalyzed three-component addition of carbonyl compounds with 1,2,3-triazoles and indoles.

A facile and efficient acid-catalyzed three-component reaction of indoles, 1-tosyl-1,2,3-triazoles and carbonyl compounds has been developed. The use of TsOH with a small amount of water significantly promoted the reaction yield. This method provided a general and one-pot approach for the synthesis of structurally diverse C3-alkylated indole derivatives. The alkylation exclusively occurred at the N2 position of triazoles. Various functional groups were tolerated under the optimized simple reaction conditions.

Isoform Specificity of PKMs during Long-Term Facilitation in Aplysia Is Mediated through Stabilization by KIBRA.

Persistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems, including the hermaphrodite marine mollusk, Aplysia californica Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform is required, the kidney and brain expressed adaptor protein (KIBRA) is also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform-specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant-negative-PKMs to erase LTF is correlated with isoform-specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an α-helix "handle" in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in AplysiaSIGNIFICANCE STATEMENT Long-lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs are not isoform-specific, isoform specificity is defined by a "handle" helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.

Three-Component Cascade Synthesis of Carbazoles through [1s,6s] Sigmatropic Shift under Metal-Free Conditions.

A novel method was developed for the synthesis of substituted carbazoles from commercially available starting materials under metal-free conditions. This strategy involves a [1s,6s] sigmatropic shift step and introduces an electron-withdrawing ester substituent at the C2 position of the carbazole ring. The present protocol afforded the desired carbazole derivatives with good regioselectivity and well functional group tolerance. DFT calculations were carried out to support the reaction pathway.

Formation and Evolution of Solvent-Extracted and Nonextractable Environmentally Persistent Free Radicals in Fly Ash of Municipal Solid Waste Incinerators.

Environmentally persistent free radicals (EPFRs) are emerging contaminants occurring in combustion-borne particulates and atmospheric particulate matter, but information on their formation and behavior on fly ash from municipal solid waste (MSW) incinerators is scarce. Here, we have found that MSW-associated fly ash samples contain an EPFR concentration of 3-10 × 1015 spins g-1, a line width (ΔHp-p) of ∼8.6 G, and a g-factor of 2.0032-2.0038. These EPFRs are proposed to be mixtures of carbon-centered and oxygen-centered free radicals. Fractionation of the fly ash-associated EPFRs into solvent-extracted and nonextractable radicals suggests that the solvent-extracted part accounts for ∼45-73% of the total amount of EPFRs. Spin densities of solvent-extracted EPFRs correlate positively with the concentrations of Fe, Cu, Mn, Ti, and Zn, whereas similar correlations are comparatively insignificant for nonextractable EPFRs. Under natural conditions, these two types of EPFRs exhibit different stabilization that solvent-extracted EPFRs are relatively unstable, whereas the nonextractable fraction possesses a long life span. Significant correlations between concentrations of solvent-extracted EPFRs and generation of hydroxyl and superoxide radicals are found. Overall, our results suggest that the fractionated solvent-extracted and nonextractable EPFRs may experience different formation and stabilization processes and health effects.

Novel Efficient Bioprocessing of Marine Chitins into Active Anticancer Prodigiosin.

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65-6.15 containing 1% α-chitin, 0.6% casein, 0.05% K2HPO4, and 0.1% CaSO4. Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO4 was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC50 values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC50 values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs.

Polymorphism rs189037C > T in the promoter region of the ATM gene may associate with reduced risk of T2DM in older adults in China: a case control study.

BACKGROUND: Recent evidence indicates that ataxia telangiectasia mutated (ATM) is a cytoplasmic protein that involves in insulin signaling pathways. When ATM gene is mutated, this event appears to contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Up to date, little information about the relationship between ATM gene polymorphism and T2DM is available. This study aimed to explore potential association between a genetic variant [single nucleotide polymorphism (SNP), i.e. rs189037C > T] in the ATM promoter region and T2DM in older adults in China. METHODS: We conducted a 1:1 age- and sex-matched case-control study. It enrolled 160 patients including 80 type 2 diabetic and 80 nondiabetic patients who were aged 60 years and above. Genotyping of the polymorphism rs189037 in the promoter of the ATM gene was performed using polymerase chain reaction-restriction fragment length polymorphism. Chi-square test or Fisher's exact test (when an expected cell count was <5) and unpaired Student's t test were used for categorical and continuous variables, respectively. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) with adjustment for factors associated with T2DM. RESULTS: Significant association was found between the genotypes of the ATM rs189037 polymorphism and T2DM (P = 0.037). The frequency of CT genotype is much higher in patients without T2DM than in diabetics (60.0% versus 40.0%, P = 0.012). After adjustment of the major confounding factors, such difference remained significant (OR for non-T2DM is 2.62, 95%CI = 1.05-6.53, P = 0.038). Similar effect of CT genotype on T2DM was observed in male population (adjusted: OR = 0.27, 95%CI = 0.09-0.84, P = 0.024). In addition, the percentage of TT genotype in diabetics with coronary artery disease (CAD) was considerably lower than in those without CAD (17.9% versus 61.5%, P = 0.004). CONCLUSIONS: Our study suggests that the ATM rs189037 polymorphism is associated with reduced risk of T2DM in older adult population in China. Specifically, CT heterozygote seems to be associated with a lower risk of T2DM than CC or TT genotype, especially in male older adults. Moreover, TT genotype may reduce the risk of CAD in diabetic patients.

One-Pot Cascade Synthesis of Substituted Carbazoles from Indoles, Ketones, and Alkenes Using Oxygen as the Oxidant.

An efficient one-pot two-step indole-to-carbazole strategy has been developed. This transition metal-free methodology uses oxygen as the sole oxidant and starts from cheap and readily available indoles, ketones, and alkenes. The present protocol efficiently enables the assembly of a diverse array of substituted carbazole products with good regioselectivity and broad tolerance of functional groups.

Modular Synthesis of Carbazole-Based Conjugated Molecules through a One-Pot Annulation/Dehydrogenation Sequence.

An efficient one-pot indole-to-carbazole strategy with cyclohexanones as the aryl source is described. This cascade carbazole formation is enabled by the NH4I-catalyzed annulation of indoles, cyclohexanones, and alkenes and subsequent dehydrogenative aromatization. The present work provides a modular synthesis of arylcarbazoles, benzocarbazoles, and naphthocarbazoles with excellent regioselectivity and broad functional group tolerance. More than 40 benzo-fused carbazoles were synthesized, and the UV-vis absorption and photoluminescent spectra of some products were measured to study their photophysical properties.