Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Exploiting biochemical data to improve osteosarcoma diagnosis with deep learning.

Early and accurate diagnosis of osteosarcomas (OS) is of great clinical significance, and machine learning (ML) based methods are increasingly adopted. However, current ML-based methods for osteosarcoma diagnosis consider only X-ray images, usually fail to generalize to new cases, and lack explainability. In this paper, we seek to explore the capability of deep learning models in diagnosing primary OS, with higher accuracy, explainability, and generality. Concretely, we analyze the added value of integrating the biochemical data, i.e., alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and design a model that incorporates the numerical features of ALP and LDH and the visual features of X-ray imaging through a late fusion approach in the feature space. We evaluate this model on real-world clinic data with 848 patients aged from 4 to 81. The experimental results reveal the effectiveness of incorporating ALP and LDH simultaneously in a late fusion approach, with the accuracy of the considered 2608 cases increased to 97.17%, compared to 94.35% in the baseline. Grad-CAM visualizations consistent with orthopedic specialists further justified the model's explainability.

Adipocyte­rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator­activated receptor gamma/ABCG2 in epithelial ovarian cancer.

The effects of adipocyte­rich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyte­rich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARM­associated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro. Specifically, the peroxisome proliferator­activated receptor Î³ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3­shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARM­educated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.

Cu(I) Complexes Catalyzed the Dehydrogenation of N-Heterocycles.

A copper-catalyzed method for the dehydrogenation of various nitrogen-containing heterocycles to furnish quinolines and indoles has been developed. A range of 1,2,3,4-tetrahydroquinolines underwent dehydrogenation by employing 2 mol % of copper complex Cat 3 as a catalyst and using O2 as an oxidant at 120 °C in 1,2-dichlorobenzene to afford the desired quinolines. The method enables the dehydrogenation of a variety of indolines in the presence of 2 mol % of copper complex Cat 2, using 10 mol % of TEMPO as an additive and O2 as an oxidant under room temperature in tetrahydrofuran to furnish indoles in high yields. Mechanistic studies suggested that the dehydrogenative activity is ascribed to the formation of a copper(II) active species from copper(I) complexes oxidized by O2, which was proved by high-resolution mass spectrometry (HRMS). The copper-catalyzed dehydrogenation reaction proceeds via a superoxide radical anion (·O2-) as proved by electron paramagnetic resonance (EPR) spectrometry. In situ infrared spectroscopy revealed that the dihydroquinoline intermediate was formed in the dehydrogenation of 1,2,3,4-tetrahydroquinolines.

Prognostic analysis of mutated genes and insight into effects of DNA damage and repair on mutational strand asymmetries in gastric cancer.

Gastric cancer (GACA) is a complex and multifaceted disease influenced by a variety of environmental and genetic factors. Somatic mutations play a major role in its development, and their characteristics, including the asymmetry between two DNA strands, are of great interest and appear as a signal of information and guidance, revealing mechanisms of DNA damage and repair. Here, we analyzed the impact of High-frequency mutated genes on patient prognosis and found that the effect of expression levels of tumor protein p53 (TP53) and lysine methyltransferase 2C (KMT2C) genes remained high throughout the development of GACA, with similar expression patterns. After investigating mutation asymmetry across mutagenic processes, we found that transcriptional asymmetry was dominated by T > G mutations under the influence of transcription couples repair and damage. The apolipoprotein B mRNA editing enzyme catalytic polypeptide like (APOBEC) enzyme that induces mutations during DNA replication has been identified here and we identified a replicative asymmetry, which was dominated by C > A mutations in left-replicating. Strand bias in different mutation classes at transcription factor binding sites and enhancer regions were also confirmed, which implies the important role of non-coding regulatory elements in the occurrence of mutations. This work systematically describes mutational strand asymmetries in specific genomic regions, shedding light on the DNA damage and repair mechanisms underlying somatic mutations in cohorts of GACA patients with gastric cancer.

Effect of Garlic Straw with Silage Corn Stalks on Hu Sheep Rumen Fermentation and Microbial Community In Vitro.

Garlic, an important economic crop, provides nutrient-rich straw. When appropriately balanced with silage corn stalks, it is a high-quality forage resource. However, studies on the impact of garlic straw with silage corn stalks on Hu sheep's digestive metabolism and rumen microbiota are scarce. In this study, different addition ratios of garlic straw and silage corn stalks were utilized for in vitro experiments. We designed six experimental groups (CON, G0, G20, G40, G60, G80, and G100) based on varying ratios of garlic straw to silage corn stalks. Rumen microbiota was analyzed through 16S rRNA sequencing. Nutrient composition analysis indicated that garlic straw's relative feeding value (RFV) closely resembled that of silage corn stalks. After 24 h of fermentation, dry matter digestibility and in vitro gas production significantly increased, reaching peak values at a 60% addition ratio. Furthermore, volatile fatty acids (VFAs) such as acetic, propionic, and butyric acid exhibited elevated contents, with the highest yields observed at 60% inclusion. At the genus level, Prevotella, Rikenellaceae RC9 gut group, and Succiniclasticum were identified as the dominant bacterial groups. The gas production test showed a significant decrease in the G80 group compared to others. Microbial analysis revealed a higher abundance of Prevotella in G80 compared to G20, offering valuable insights for reducing greenhouse gas emissions from ruminant animals. Finally, this study predicted the impact of garlic straw with silage corn stalks' addition on Hu sheep's metabolic pathways and biological functions of the rumen microbiota. This research highlights the potential for effectively utilizing garlic straw as a feed resource for Hu sheep and proposes a rational proportion for combining garlic straw with silage corn stalks.

The Influencing Factors of "Post-African Swine Fever" Pig Farm Biosecurity: Evidence from Sichuan Province, China.

Effective biosecurity measures are crucial in controlling and preventing major pig diseases, ultimately ensuring farm income and social stability. This study extracted data from 205 farmer surveys in Sichuan Province, China, to construct a biosecurity index system for pig farms. The biosecurity levels of pig farms were evaluated using a projection pursuit method to identify weak areas. The Tobit model was then utilized to determine the factors that influenced the biosecurity levels. The results indicated that the overall biosecurity levels of the pig farms were low. The study found that the average biosecurity score among farms was 0.61, with a minimum score of 0.37 and a maximum score of 0.89 (on a scale of 0 to 1). These results suggest that there are significant differences in biosecurity levels among the farms. The study also found that the scores for first-level indicators related to breeding environment management, as well as second-level indicators related to personnel management and awareness of African swine fever prevention and control, were significantly lower than scores for other indicators in the farmers' biosecurity systems. This study investigated the factors influencing biosecurity on farms and found that technical training, farm size, income share, production organization, and government inspections had a significant impact on the level of biosecurity implemented. This study emphasizes the significance of biosecurity in enhancing pig farm biosecurity and its role in improving farm resilience to major animal diseases like African swine fever. It also provides valuable insights for policymakers to make informed decisions regarding related policies.

Genomic Features and Comparative Genomic Analysis of Streptococcus sp. v1. nov., Isolated from an Endophthalmitis Patient.

Endophthalmitis is an acute inflammatory intraocular condition that can cause permanent vision loss. The treatment strategy and visual outcome partly depend on the identification of the agents of pathogens. In this study, metagenomic sequencing was conducted to investigate the microbial and antibiotic resistance genes (ARGs) composition in the vitreous (intraocular body fluid) of an endophthalmitis patient, who progressed rapidly and accompanied by severe pain. Metagenomic sequencing data revealed that the vitreous sample was predominated by Streptococcus, with a low-diversity microbiome in the vitreous. This strain harbor's the ARGs mainly against beta-lactam, macrolide-lincosamide-streptogramin, and multidrug. Additionally, metagenome-assembled genome sequence of Streptococcus sp. v1. nov. was identified. The Tetra Correlation Search (TCS) analysis uncovered that the closest relative of the Streptococcus sp. v1. nov. was Streptococcus mitis SK321. Pan/core genome analysis for Streptococcus sp. v1. nov. and TCS top 25 hits strains revealed that most unique genes of Streptococcus sp. v1. nov. were linked to ATP-binding cassette transport system, which could indicate unique virulence and pathogenic potentials of Streptococcus sp. v1. nov. In addition, a total of 7 virulence factors were identified, and the overwhelming of them were classified into "offensive virulence factors". The high pathogenicity of Streptococcus sp. v1. nov. could be a reason for the patient's rapid disease progression. Our study was first isolated an ocular pathogen with highly virulent based on metagenomic sequencing and bioinformatics analysis, which has important reference value for revealing the composition and genome characteristics of pathogens in endophthalmitis patient in the future.

Astrocytes in the spinal cord contributed to acute stress-induced gastric damage via the gap junction protein CX43.

Rat restraint water-immersion stress (RWIS) is a compound stress of high intensity and is widely used to study the pathological mechanisms of stress gastric ulcers. The spinal cord, as a part of the central nervous system, plays a dominant role in the gastrointestinal tract, but whether the spinal cord is involved in rat restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of spinal astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, connexin 43 (Cx43), and p-ERK1/2 during RWIS by immunohistochemistry and Western blotting. In addition, we intrathecally injected the astrocytic toxin L-a-aminoadipate (L-AA), gap junction blocker carbenoxolone (CBX), and ERK1/2 signaling pathway inhibitor PD98059 to explore the role of astrocytes in the spinal cord in RWIS-induced gastric mucosal damage and its possible mechanism in rats. The results showed that the expression of GFAP, c-Fos, Cx43, and p-ERK1/2 was significantly elevated in the spinal cord after RWIS. Intrathecal injection of both the astrocyte toxin L-AA and the gap junction blocker CBX significantly attenuated RWIS-induced gastric mucosal damage and decreased the activation of astrocytes and neurons induced in the spinal cord. Meanwhile, the ERK1/2 signaling pathway inhibitor PD98059 significantly inhibited gastric mucosal damage, gastric motility and RWIS-induced activation of spinal cord neurons and astrocytes. These results suggest that spinal astrocytes may regulate the RWIS-induced activation of neurons via CX43 gap junctions and play a critical role in RWIS-induced gastric mucosa damage through the ERK1/2 signaling pathway.

The influence of parental awareness of the "Chinese double reduction" policy on junior high school students' extracurricular physical exercise.

Objective: In this study, we aimed to explore the relationship between parental cognitive awareness (criticality, disruption and novelty cognition) of DBR, educational anxiety, and attitudes toward students' physical exercise and students' extracurricular physical exercise so as to construct and verify a conditional process model. Methods: We adopted a stratified random cluster sampling approach and conducted a nationwide questionnaire survey with 2,700 junior high school students and their parents across 9 provinces, municipalities and autonomous regions. Results: Parents generally had a certain degree of cognitive awareness of DBR. Criticality cognition and disruption cognition had a significant positive impact on junior high school students' extracurricular physical exercise (ß = 0.24, p < 0.01; ß = 0.04, p < 0.05), but the effect of novelty cognition was not significant (ß = -0.04, p = 0.06). Parents' educational anxiety played a significant mediating role in parents' cognition of DBR and students' extracurricular physical exercise (criticality cognition: ß = 0.10, 95% CI: 0.03-0.06; disruption cognition: ß = 0.37, 95% CI: 0.31-0.42). Parents' attitude toward students' exercise also played a significant positive moderating effect in the mediation model (criticality cognition: ß = 0.014, 95% CI: 0.002-0.031; disruption cognition: ß = 0.010, 95% CI: 0.007-0.013). Conclusion: Parents' novelty, disruption, and criticality cognition of DBR have different effects on parents' education anxiety and students' extracurricular physical exercise, in which parental educational anxiety mediates the influence of DBR cognition on students' extracurricular physical exercise, while attitudes toward students' extracurricular physical exercise positively moderates the mediating effect.

[Clinical Characteristics of Obstructive Sleep Apnea and Comorbid Primary Aldosteronism].

Objective: To explore the characteristics of patients with obstructive sleep apnea (OSA) and comorbid primary aldosteronism (PA) and to explore the relevant factors affecting plasma aldosterone concentration. Methods: A total of 105 patients diagnosed with PA and admitted at West China Hospital, Sichuan University between January 2016 and December 2021 were retrospectively analyzed. The subjects were divided into a PA with comorbid snoring group (n=20) and a PA with comorbid OSA group (n=85) based on the results of polysomnography (PSG). The PA with comorbid OSA group was further divided into mild, moderate, and severe subgroups according to the apnea-hypopnea index (AHI). A total of 85 outpatients diagnosed with OSA were included as the control group. Demographic, clinical, biochemical, and PSG data were compared between the groups. Results: Compared with patients with only OSA, a significantly higher proportion of patients with OSA and comorbid PA had hypertension and elevated levels of systolic and diastolic blood pressure (P<0.05). In addition, patients with OSA and comorbid PA had significantly increased AHI and significantly decreased mean oxygen saturation and sleep efficiency (P<0.05). The more severe the OSA was, the higher levels of BMI, cholesterol, low-density lipoprotein, and uric acid the PA patients had. Linear regression analysis showed that the lowest oxygen saturation (ß=－0.222, P=0.045) was negatively correlated with plasma aldosterone concentration. Conclusion: Comorbidity with PA can aggravate the clinical manifestations of OSA, while OSA further disrupted the metabolism of lipids and uric acid in PA patients. Plasma aldosterone concentrations in patients with comorbid OSA and PA were affected by the lowest oxygen saturation level.

Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp2)-Bromides as HAT Reagents.

N-Demethylation of trialkylamines is a useful transformation, but typically requires harsh reaction conditions and stepwise procedures, as well as judicious protection of labile functional groups. Herein we report a mild, catalytic approach for the demethylation of trialkylamines by utilizing photoinduced nickel catalysis wherein C(sp2)-bromides serve as hydrogen-atom transfer (HAT) reagents. This method achieves direct demethylation of trialkylamines with wide functional group compatibility, making it highly suitable for late-stage derivatization of complex molecules. Mechanistic investigations provide evidence that C(sp2) radicals generated via photoinduced Ni-C(sp2) bond homolysis are involved in hydrogen atom abstraction from trialkylamines. Utilizing steric control of the C(sp2)-bromides, our HAT approach achieves demethylation with excellent site selectivity in the presence of benzyl-substituted amines, which is complementary to the selectivity of classical approaches that afford debenzylation product instead.

Experimental study of transcranial pulsed current stimulation on relieving athlete's mental fatigue.

Objective: To explore the effect of independently developed transcranial pulsed current stimulation (tPCS) on alleviating athlete's mental fatigue. Methods: A total of 60 college athletes were randomly divided into the active stimulation group (current intensity:1.5 mA, lasting for 15 min) and the sham stimulation group. Subjective questionnaires, behavior test, and functional near-infrared spectroscopy (fNIRS) test were conducted before and after the experiment. Two-way ANOVA with repeated measures was used to compare the differences in mental fatigue indexes before and after the two experimental conditions. Results: After 7 days of exercise training, there was a significant difference in the main effect of the time factor in all indexes of the two groups (p < 0.05). The scores of rated perceived exertion (RPE) scale, positive and negative affect schedule (PANAS), critical flicker frequency (CFF), and reaction time (RT), in the tPCS treatment group, were better than those in the sham stimulation group (p < 0.05). After 7 days of exercise training, all the subjects had different degrees of athlete's mental fatigue; the subjects in the active stimulation group have a good evaluation of the tPCS developed by the research group without adverse actions. Conclusion: tPCS intervention can improve emotional state, reduce the subjective evaluation of fatigue, improve behavioral levels such as attention and reaction time and increase cerebral prefrontal blood flow and oxygen supply.

Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related IncRNAs in Lung Adenocarcinoma.

Lung cancer is a fatal disease with high morbidity and mortality. As a major type of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) has come into the focus of the biological and clinical research. Nevertheless, potential functions of N6-methyladenosine (m6A) methylation-related long non-coding RNAs (lncRNAs) in the tumor immune microenvironment (TIME) remain unclear. Here, we analyzed RNA-seq data of 522 samples from the TCGA-LUAD project. Based on integrative analyses of lncRNA, immune, and clinical profiles, we developed a computational method to determine the characteristics of lncRNAs as an indicators of immune cell infiltration in LUAD patients. Subsequently, we investigated the influence of m6A-related lncRNAs on prognosis and immunotherapy in patients with LUAD. We identified 24 m6A-related lncRNAs that were related to LUAD prognosis and clustered in two molecular subtypes (clusters 1 and 2). Our results suggest that cluster 1 was significantly related to downregulation of PD-L1, enhancement of immune cell infiltration, and good prognosis. Furthermore, p53 and mTOR pathways were enriched in cluster 1, whereas in the cluster 2, PPAR was uncommonly enriched. Patients with LUAD who had lower risk scores exhibited higher immunoscores and lower expression levels of programmed cell death-ligand 1, compared with patients who had higher risk scores. Finally, m6A-related lncRNAs were implicated in the TIME; our findings indicate that these lncRNAs are critical within the TIME in LUAD. These signatures are promising as potential targets for improved LUAD immunotherapy.

Cancer Risk and Mutational Patterns Following Organ Transplantation.

The rapid development of medical technology and widespread application of immunosuppressive drugs have improved the success rate of organ transplantation significantly. However, the use of immunosuppressive agents increases the frequency of malignancy greatly. With the prospect of "precision medicine" for tumors and development of next-generation sequencing technology, more attention has been paid to the application of high-throughput sequencing technology in clinical oncology research, which is mainly applied to the early diagnosis of tumors and analysis of tumor-related genes. All generations of cancers carry somatic mutations, meanwhile, significant differences were observed in mutational signatures across tumors. Systematic sequencing of cancer genomes from patients after organ transplantation can reveal DNA damage and repair processes in exposed cancer cells and their precursors. In this review, we summarize the application of high-throughput sequencing and organoids in the field of organ transplantation, the mutational patterns of cancer genomes, and propose a new research strategy for understanding the mechanism of cancer following organ transplantation.

Population structure of 3907 worldwide pigs and the introgression of Chinese indigenous pigs by European pigs.

With the improvement in sequencing technology and the decrease in sequencing cost, increasing amounts of genomic data for pigs have been uploaded to public databases. However, no researchers have to date integrated all currently available data to uncover the global genetic status of pigs. Meanwhile, little is known about the introgression from European to Chinese pigs and its underlying influences. Therefore, we integrated the effective genotype data of 3907 pigs from 193 populations worldwide using population genetic analysis, gene flow analysis and a sharing-IBD study. These findings illustrate not only the population structure of 59 Chinese native breeds and others but also the amounts of gene flow and introgression that have occurred between Western and Chinese pigs. In addition, we demonstrate the presence of introgressed European haplotypes in Chinese indigenous breeds and identify relevant introgressed regions that contain genes associated with growth and feed efficiency. Moreover, we compare the introgression patterns of Western and Chinese pigs and further discuss possible explanations for why the level of introgression differs between Chinese pig breeds and Western modern breeds. Collectively, this study provides a fine global population structure analysis of pigs and presents evidence of European pigs being interbred with local breeds in China.

Transcriptome Analysis Reveals the Differentially Expressed Genes Associated with Growth in Guangxi Partridge Chickens.

The Guangxi Partridge chicken is a well-known chicken breed in southern China with good meat quality, which has been bred as a meat breed to satisfy the increased demand of consumers. Compared with line D whose body weight is maintained at the average of the unselected group, the growth rate and weight of the selected chicken group (line S) increased significantly after breeding for four generations. Herein, transcriptome analysis was performed to identify pivotal genes and signal pathways of selective breeding that contributed to potential mechanisms of growth and development under artificial selection pressure. The average body weight of line S chickens was 1.724 kg at 90 d of age, which showed a significant increase at 90 d of age than line D chickens (1.509 kg), although only the internal organ ratios of lung and kidney changed after standardizing by body weight. The myofiber area and myofiber density of thigh muscles were affected by selection to a greater extent than that of breast muscle. We identified 51, 210, 31, 388, and 100 differentially expressed genes (DEGs) in the hypothalamus, pituitary, breast muscle, thigh muscle, and liver between the two lines, respectively. Several key genes were identified in the hypothalamus-pituitary-muscle axis, such as FST, THSB, PTPRJ, CD36, PITX1, PITX2, AMPD1, PRKAB1, PRKAB2, and related genes for muscle development, which were attached to the cytokine-cytokine receptor interaction signaling pathway, the PPAR signaling pathway, and lipid metabolism. However, signaling molecular pathways and the cell community showed that elevated activity in the liver of line S fowl was mainly involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules, and signal transduction. Collectively, muscle development, lipid metabolism, and several signaling pathways played crucial roles in the improving growth performance of Guangxi Partridge chickens under artificial selection for growth rate. These results support further study of the adaptation of birds under selective pressure.

How anammox process resists the multi-antibiotic stress: Resistance gene accumulation and microbial community evolution.

The effects of multiple antibiotics on the anaerobic ammonia oxidation (anammox) process were investigated. The resistance of the anammox system to high-concentration antibiotics was also demonstrated through gradual acclimation experiments. Inhibition of the anammox process (R1) occurred when the concentrations of erythromycin (ERY), sulfamethoxazole (SMX) and tetracycline (TC) were 0.1, 5.0 and 0.1 mg L-1, respectively. The nitrogen removal efficiency (NRE) of R1 was reduced from 97.2% to 60.7% within 12 days and then recovered to 88.9 ± 9.5% when the nitrogen loading declined from 4.52 ± 0.69 to 2.11 ± 0.58 kg N m-3 d-1. Even when the concentrations of ERY, SMX and TC were as high as 1.0, 15.0 and 1.0 mg L-1, respectively, R1 maintained stable operation. The increases in the abundance of antibiotic resistance genes (ARGs) and in extracellular polymeric substances (EPS) content showed that the anammox process alleviated stress from multiple antibiotics mainly by producing ARGs and secreting EPS. The molecular docking simulation results illustrated the potential binding sites between ammonium transporter and different antibiotics. The upregulation of functional gene expression and the stable abundance of Candidatus Kuenenia in R1 compared with that in the control suggested that the R1 reactor generally maintained more stable long-term operation. This work provides a new understanding of the application of the anammox process to treat wastewater containing multiple antibiotics.

Site-Selective α-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis.

Trialkylamines are widely found in naturally occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and preclinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective α-C(sp3)-H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery, and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between α-amino C(sp3)-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3)-C(sp3) bond with the more-crowded α-amino radical, with the overall selectivity guided by the Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C-C bonds from a diverse set of trialkylamines with high levels of site selectivity and preparative utility. Simple correlation of site selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, hold potential to streamline complex trialkylamine synthesis and accelerate small-molecule drug discovery.

Late-Stage N-Me Selective Arylation of Trialkylamines Enabled by Ni/Photoredox Dual Catalysis.

The diversity and wide availability of trialkylamines render them ideal sources for rapid construction of complex amine architectures. Herein, we report that a nickel/photoredox dual catalysis strategy affects site-selective α-arylation of various trialkylamines. Our catalytic system shows exclusive N-Me selectivity with a wide range of trialkylamines under mild conditions, even in the context of late-stage arylation of pharmaceutical compounds bearing this common structural motif. Mechanistic studies indicate the unconventional behavior of Ni catalyst upon intercepting the α-amino radicals, in which only the primary α-amino radical undergoes a successful cross-coupling process.