Visible-light-induced alkyl-arylation of olefins via a halogen-atom transfer process.

Visible-light-induced three-component 1,2-alkyl-arylation of alkenes and alkyl radical addition/cyclization of acrylamides have been realized via a photocatalytic halogen-atom transfer (XAT) process. This metal-free protocol utilizes readily available tertiary alkylamine as both an electron donor and an XAT reagent for the activation of alkyl halides using naphthalimide (NI)-based organic photocatalysts. This process features broad substrate scope and good functional group tolerance under mild conditions, and could be effectively applied to a variety of medicinally relevant substrates.

Submucosal Trans-Septal Suturing Technique After a Septal Extension Graft with Porous High-Density Polyethylene: A Technical Report.

BACKGROUND: Porous high-density polyethylene (pHDPE) is an alternative material for a septal extension graft (SEG) in oriental rhinoplasty when autologous cartilage is limited. Although nasal packing (NP) and trans-septal suturing (TSS) techniques are routine procedures to obviate the dead space after septoplasty, they are associated with certain discomforts and complications. OBJECTIVE: To investigate the application of a submucosal trans-septal suturing (STSS) technique after SEG with pHDPE. METHODS: A prospective study was conducted on 60 female participants who underwent SEG with pHDPE. The participants were randomly divided into the NP group and STSS group. The extra surgical duration of NP and STSS, pain, nasal obstruction, and sleeping disturbance as well as postoperative complications were recorded and compared between groups. RESULTS: No significant difference was found between group NP and group STSS in terms of mean age. The mean extra surgical duration of group STSS was significantly longer than group NP. There were significant higher pains of group NP at 24 hours and 48 hours postoperatively, compared with group STSS. The NP group also experienced significantly more nasal obstruction and sleep disturbance within 48h postoperatively compared to the STSS group. There was one infection in each group, minor bleeding in two NP patients, and one STSS patient. There was no major bleeding, hematoma, graft exposure, or septal perforation in both groups. CONCLUSION: Although STSS needs a longer extra surgical duration than NP, it significantly improves the patient's postoperative comfort with a faster return to normal respiration compared to NP. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Functions and regulations of insect gut bacteria.

The insect gut is a complicated ecosystem that inhabits a large number of symbiotic bacteria. As an important organ of the host insect, the symbiotic bacteria of the insect gut play very important roles in regulating physiological and metabolic processes. Recently, much progress has been made in the study of symbiotic bacteria in insect guts with the development of high-throughput sequencing technology and molecular biology. This review summarizes the primary functions of symbiotic bacteria in insect guts, such as enhancing insecticide resistance, facilitating food digestion, promoting detoxification, and regulating mating behavior and egg hatching. It also addresses some possible pathways of gut bacteria symbiont regulation governed by external habitats, physiological conditions and immunity of the host insect. This review provides solid foundations for further studies on novel theories, new technologies and practical applications of symbiotic bacteria in insect guts. © 2024 Society of Chemical Industry.

Selective Reduction of Triple Bond via Proton-Coupled Electron Transfer for the Synthesis of α,ß-Unsaturated γ-Lactams.

Described herein is the development of a visible-light-induced photoredox 1,6-enyne reductive cyclization via selective reduction of a triple bond instead of an activated double bond. The selective 1,6-enyne radical cyclization/carbon═carbon double bond cleavage provided a straightforward route to structurally valuable α,ß-unsaturated γ-lactams. TEMPO-trap experiments, control experiments, and DFT calculations have offered evidence supporting the possible catalytic cycle.

A review of 10 patients treated with the masquelet technique and microsurgical technique combined for Gustilo type III open tibial fractures.

BACKGROUND: Open tibial fractures often include severe bone loss and soft tissue defects and requires complex reconstructive operations. However, the optimal treatment is unclear. METHODS: This retrospective study enrolled patients with Gustilo type III open tibial fractures from January 2018 to January 2021 to assess the clinical utility of Masquelet technique together with microsurgical technique as a combined strategy for the treatment of open tibial fractures. The demographics and clinical outcomes including bone union time, infection, nonunion and other complications were recorded for analysis. The bone recovery quality was evaluated by the AOFAS Ankle-Hindfoot Scale score and the Paley criteria. RESULTS: We enrolled 10 patients, the mean age of the patients and length of bone defects were 31.7 years (range, 23-45 years) and 7.5 cm (range, 4.5-10 cm) respectively. Bone union was achieved for all patients, with an average healing time of 12.2 months (range, 11-16 months). Seven patients exhibited a bone healing time of less than 12 months, whereas 3 patients exhibited a bone healing time exceeding 12 months. No significant correlation was found between the length of bone loss and healing time. In addition, no deep infection or nonunion was observed, although 2 patients experienced wound fat liquefaction with exudates and 1 patient presented with a bloated skin flap. The average AOFAS Ankle-Hindfoot Scale score was 80.5 (range, 74-85), and all patients were evaluated as good or exellent based on the Paley criteria. CONCLUSIONS: Our study indicated that the use of the Masquelet technique and the microsurgical technique as a combined strategy is safe and effective for the treatment of Gustilo type III open tibial fractures.

Rapid and Sensitive Detection of Fentanyl and Its Analogs by a Novel Chemiluminescence Immunoassay.

BACKGROUND: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods. METHODS: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS. RESULTS: When applied to clinical samples, the novel chemiluminescence immunoassay can detect low positive fentanyl missed by routine screening immunoassays, with a limit of detection of 0.8 pg/mL in human urine. When applied to environmental samples, the assay can detect levels as low as 0.25 pg fentanyl per inch2 of environment surface. Assay turnaround time is less than 1 h, with inexpensive equipment and the potential for high-throughput automation or in-field screening. CONCLUSIONS: We have established a novel assay that may have broad applications in clinical, environmental, occupational, and forensic scenarios for detection of trace amounts of fentanyl and its analogs.

Oleanane and 30-noroleanane triterpenoids from the roots of Paeonia lactiflora.

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.

Photocatalytic Proton-Coupled Electron Transfer Enabled Radical Cyclization for Isoquinoline-1,3-diones Synthesis.

Radical cyclization has been demonstrated to be an efficient method to access functionalized heterocycles from easily accessible raw materials. Described herein is the development of a photocatalytic proton-coupled electron transfer (PCET) strategy for the synthesis of isoquinoline-1,3-diones using readily prepared naphthalimide (NI)-based organic photocatalysts. The process features free metal-complex photocatalysts, acids, and mild reaction conditions. This mild radical cyclization protocol has a broad substrate scope and can be effectively applied to a variety of medicinally relevant substrates. Furthermore, control experiments were conducted to elucidate the mechanism of this visible light-induced methodology.

Gut bacteria mediated adaptation of diamondback moth, Plutella xylostella, to secondary metabolites of host plants.

IMPORTANCE: In this study, we identify an important role of gut bacteria in mediating the adaptation of diamondback moth (DBM) to plant secondary metabolites. We demonstrate that kaempferol's presence in radish seedlings greatly reduces the fitness of DBM with depleted gut biota. Reinstatement of gut biota, particularly Enterobacter sp. EbPXG5, improved insect performance by degrading kaempferol. This bacterium was common in the larval gut of DBM, lining the epithelium as a protective film. Our work highlights the role of symbiotic bacteria in insect herbivore adaptation to plant defenses and provides a practical and mechanistic framework for developing a more comprehensive understanding of insect-gut microbe-host plant co-evolution.

Silver-catalyzed nitrosation and nitration of aromatic amides using NOBF4.

Divergent aromatic ring nitrosation and nitration of aromatic amides are reported using NOBF4 as the electrophile under silver-catalyzed conditions. The reactions proceed efficiently with a wide range of compatible functionalities providing ortho-position nitrosation products, deacylation nitrosation products, and nitration products from different tertiary and secondary aromatic amides.

Gut microbial diversity and function analysis of the final-instar larvae of Protohermes xanthodes (Megaloptera: Corydalidae).

Protohermes xanthodes (Megaloptera, Corydalidae, Protohermes), widespread species in China, is an important insects treated as food and medicine for aquaculture. In this study, the gut microbiota was investigated by 16S rRNA microbial profiling. A total of 600 Amplicon Sequence Variants (ASV) were identified, Proteobacteria and Firmicutes were the main dominant phyla, and 27 genera ran through the entire digestive tract, mainly Hafnia-Obesumbacterium (Proteobacteria), Lactobacillus and Lactococcus (Firmicutes). The PICRUSt2 functional prediction of gut microbiota showed that the foregut abundant pathways related to metabolism, environmental information processing, and genetic information processing. while the midgut had the most abundant metabolic and environmental information processing pathways, including the prominent phosphotransferase system (PTS), propionate metabolism, and ß-lactam resistance. The hindgut had the weakest metabolic function, but its genetic information processing was more abundant than the foregut and midgut. Additionally, 26 strains of bacteria were isolated from the midgut microorganisms, with Firmicutes being the dominant bacteria, and some of the purified bacteria had potential probiotic and anti-pathogen functions. These findings suggest that there are differences in the microorganisms of the different gut floras of the larvae, and each flora has specific metabolic functions. This research could be used to further understand the function of gut microorganisms, explore the co-evolution of P. xanthodes and gut microorganisms, and promote healthy breeding based on gut microorganisms.

Potential Source and Transmission Pathway of Gut Bacteria in the Diamondback Moth, Plutella xylostella.

Plutella xylostella (L.), commonly known as the diamondback moth, is currently a major worldwide pest. Gut bacteria play an important role in the physiology and insecticide resistance of P. xylostella, but little is known about the sources and transmission routes of its gut bacteria. In this study, traditional microbial culture methods were used to analyze the sources and transmission modes of gut bacteria in P. xylostella, which could help develop pest control strategies based on gut bacteria. The main findings are as follows: gut bacterial diversity was significantly higher in P. xylostella-fed radish sprouts than those fed an artificial diet, indicating a potential association between gut bacteria and food bacteria. In addition, sequence analysis revealed the isolation of Enterobacter sp., Pantoea sp., Cedecea sp., and Pseudomonas sp. from both radish sprouts and P. xylostella. Importantly, Enterobacter sp. was found in all tested samples (radish sprouts, gut of P. xylostella, ovaries, and eggs), suggesting that bacteria acquired from food could be transferred from the gut to the ovaries and eggs. This was confirmed through experiments, which also showed that eggs could carry bacteria and transmit them to the gut, indicating vertical transmission of gut bacteria via eggs. Furthermore, the 3rd instar larvae of P. xylostella with and without gut bacteria were mixed and raised until the 4th instar. Then, we found that all the gut of the 4th instar larvae carried the same bacteria, indicating that the gut bacteria of P. xylostella can be horizontally transmitted through social behavior. This study lays a foundation for further exploration of the sources, transmission, and coevolution of the host of gut bacteria in P. xylostella, and provides new insights into pest control strategies based on the source and transmission of gut bacteria.

Gut microbiota and integrative traditional Chinese and western medicine in prevention and treatment of heart failure.

BACKGROUND: Heart failure (HF) is the terminal stage of multiple cardiovascular diseases, with high mortality and morbidity. More and more studies have proved that gut microbiota may play a role in the process of HF, which is expected to become a new therapeutic target. The combination of traditional Chinese and Western medicine has vast therapeutic potential of complementation against HF. PURPOSE: This manuscript expounds on the research progress of mechanisms of gut microbiota participating in the occurrence and prognosis of HF and the role of integrative traditional Chinese and Western medicine from 1987 to 2022. The combination of traditional Chinese and Western medicine in the prevention and treatment of HF from the perspective of gut microbiota has been discussed. METHODS: Studies focusing on the effects and their mechanisms of gut microbiota in HF and the role of integrative traditional Chinese and Western medicine were identified and summarized, including contributions from February 1987 until August 2022. The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases up to April 2023 by using the relevant keywords and operators. RESULTS: A total of 34 articles were finally included in this review.16 RCTs and 13 basic researches, and 3 clinical research studies involving 7 relevant outcome indicators(cardiac function evaluation index, changes in gut microbiota, inflammatory factors, metabolites of gut microbiota, serum nutritional index protein, quality of life score, intestinal permeability and all-cause mortality). Compared with healthy controls, serum TNF-α and TMAO levels were significantly higher in patients with heart failure [MD = 5.77, 95%CI(4.97, 6.56), p < 0.0001; SMD = 1.92, 95%CI(1.70, 2.14), p < 0.0001]. Escherichia coli and Thick-walled bacteria increased significantly [SMD = -0.99, 95%CI(-1.38, -0.61), p < 0.0001, SMD = 2.58, 95%CI(2.23, 2.93), p < 0.0001];The number of bacteroides and lactobacillus decreased [SMD = -2.29, 95%CI(-2.54, -2.04), p < 0.0001; SMD = -1.55, 95%CI(-1.8, -1.3), p < 0.0001]. There was no difference in bifidobacterium [SMD = 0.16, 95%CI(-0.22, 0.54), p = 0.42]. In the published literature, it is not difficult to see that most of the results are studied and proved based on animal experiments or clinical trials, involving the cellular level, while the mechanism and mode of action of the molecular biology of traditional Chinese medicine are less elaborated, which is related to the characteristics of multi-components and multi-targets of traditional Chinese medicine. The above are the shortcomings of published literature, which can also be the direction of future research. CONCLUSION: Heart failure patients have decreased beneficial bacteria such as Bacillus mimics and Lactobacillus in the intestinal flora and increased harmful flora like thick-walled flora. And increase the inflammatory response of the body and the expression of trimethylamine oxide (TMAO) in the serum. And The prevention and treatment of integrative traditional Chinese and Western medicine against heart failure based on gut microbiota and its metabolites is a promising research direction.

Decoding CRISPR-Cas PAM recognition with UniDesign.

The critical first step in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated (CRISPR-Cas) protein-mediated gene editing is recognizing a preferred protospacer adjacent motif (PAM) on target DNAs by the protein's PAM-interacting amino acids (PIAAs). Thus, accurate computational modeling of PAM recognition is useful in assisting CRISPR-Cas engineering to relax or tighten PAM requirements for subsequent applications. Here, we describe a universal computational protein design framework (UniDesign) for designing protein-nucleic acid interactions. As a proof of concept, we applied UniDesign to decode the PAM-PIAA interactions for eight Cas9 and two Cas12a proteins. We show that, given native PIAAs, the UniDesign-predicted PAMs are largely identical to the natural PAMs of all Cas proteins. In turn, given natural PAMs, the computationally redesigned PIAA residues largely recapitulated the native PIAAs (74% and 86% in terms of identity and similarity, respectively). These results demonstrate that UniDesign faithfully captures the mutual preference between natural PAMs and native PIAAs, suggesting it is a useful tool for engineering CRISPR-Cas and other nucleic acid-interacting proteins. UniDesign is open-sourced at https://github.com/tommyhuangthu/UniDesign.

[Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine].

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Spatial metabolomics reveal mechanisms of dexamethasone against pediatric pneumonia.

Currently, drugs are limited to treating pediatric pneumonia in clinical practice. It is urgent to find one new precise prevention and control therapy. The dynamically changing biomarkers during the development of pediatric pneumonia could help diagnose this disease, determine its severity, assess the risk of future events, and guide its treatment. Dexamethasone has been recognized as an effective agent with anti-inflammatory activity. However, its mechanisms against pediatric pneumonia remain unclear. In this study, spatial metabolomics was used to reveal the potential and characteristics of dexamethasone. Specifically, bioinformatics was first applied to find the critical biomarkers of differential expression in pediatric pneumonia. Subsequently, Desorption Electrospray Ionization mass spectrometry imaging-based metabolomics screened the differential metabolites affected by dexamethasone. Then, a gene-metabolite interaction network was built to mark functional correlation pathways for exploring integrated information and core biomarkers related to the pathogenesis and etiology of pediatric pneumonia. Further, these were validated by molecular biology and targeted metabolomics. As a result, genes of Cluster of Differentiation19, Fc fragment of IgG receptor IIb, Cluster of Differentiation 22, B-cell linker, Cluster of Differentiation 79B and metabolites of Triethanolamine, Lysophosphatidylcholine(18:1(9Z)), Phosphatidylcholine(16:0/16:0), phosphatidylethanolamine(O-18:1(1Z)/20:4(5Z,8Z,11Z,14Z)) were identified as the critical biomarkers in pediatric pneumonia. B cell receptor signaling pathway and glycerophospholipid metabolism were integrally analyzed as the main pathways of these biomarkers. The above data were illustrated using a Lipopolysaccharides-induced lung injury juvenile rat model. This work will provide evidence for the precise treatment of pediatric pneumonia.

Engineered acetaldehyde dehydrogenase for the efficient degradation of acetaldehyde.

Acetaldehyde is highly cytotoxic and widely presents in food and the environment. Aldehyde dehydrogenase (ALDH) can degrade acetaldehyde to non-toxic acetic acid, showing potential for acetaldehyde elimination. However, a lack of high-throughput methods for screening efficient variants is a significant obstacle to ALDH design. Here, we established a visualized high-throughput method to screen recombinantly expressed ALDH variants in Bacillus subtilis by fluorescent probes of dual-acceptor cyanine-based in response to NADH, the acetaldehyde degradation product. Molecular docking revealed key amino acids in the binding region of acetaldehyde to ALDH. Combined with saturation mutagenesis and visualization high-throughput methods, a variant ALDHS273N with an activity of 119.82 U·mL-1 was screened. The optimal reaction temperature and pH of ALDHS273N were 60 °C and 9.0, respectively. ALDHS273N showed stability at 30-50 °C and pH 5.0-9.0. The activity of ALDHS273N was increased to 263.52 U∙mL-1 by fermentation optimization, which was 5.58 times that of ALDHWT. The degradation rate of ALDHS273N to 100 mmol L-1 acetaldehyde was 87.34% within 2 h, which was 4.2 times that of the wild enzyme (20.81%). As far as we know, this is the ALDH with the highest activity reported so far, and it is also the first time that ALDH has been used for the efficient degradation of acetaldehyde. Overall, the reported high-throughput screening method and developed mutants represent a significant advance in green bio-elimination technologies of acetaldehyde.

Transforaminal Endoscopic Lumbar Discectomy versus Open Decompression Discectomy for Lumbar Disc Herniation.

OBJECTIVE: To compare the efficacy of transforaminal endoscopic lumbar discectomy (TELD) and open decompression discectomy (ODD) in the treatment of single-segment L4/5disc herniation. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Orthopedics, General Hospital of the Yangtze River Shipping, Jiang'an District, Wuhan, Hubei, China, from January to December 2021. METHODOLOGY: Using random number table allocation, 94 patients with lumbar disc herniation (LDH, at level L4/5) received were divided into two groups of 47 patients each in the control group treated with ODD and 47 patients in the observation group treated with TELD. The perioperative-related indexes, VAS score, ODI index, modified Macnab evaluation criteria, and the incidence of complications were compared between the two groups. RESULTS: The incision length in the observation group was shorter than that in the control group, the amount of intraoperative blood loss was less than that in the control group, and bedtime and hospital stay were shorter than that in the control group, but the operation time was longer than that in the control group, with statistically significant differences (p <0.01). The VAS score, ODI index, and incidence of postoperative complications in the observation group were lower than those in the control group at 7d, 1 month, 3 months, and 6 months after surgery, while modified Macnab evaluation criteria of lumbar function recovery were higher than that in the control group, the difference was statistically significant (p <0.01). CONCLUSION: TELD is safe and effective for patients with LDH, which can relieve postoperative pain and help restore lumbar function. KEY WORDS: Lumbar disc herniation (LDH), Transforaminal endoscopic lumbar discectomy (TELD), Open decompression discectomy (ODD), Visual analogue score (VAS), Oswestry disability index (ODI), Modified Macnab evaluation criteria.

Recent developments in the synthesis of the isoquinoline-1,3(2H,4H)-dione by radical cascade reaction.

In recent years, isoquinoline-1,3(2H,4H)-dione compounds have attracted extensive attention from synthetic chemists, with the aim of finding simple, mild, green and efficient synthetic methods. In this review, we summarize the diverse range of synthetic methods employing acryloyl benzamides as key substrates to furnish isoquinoline-1,3-diones using different radical precursors, such as those containing carbon, sulphur, phosphorus, nitrogen, silicon and bromine. This will stimulate the interest of readers to engage in research in this field.