Search

To study the dynamic compression and tensile mechanical behaviors of a bicomponent epoxy resin matrix composites, which were filled with a semi-crystalline thermoplastic Polyether-ether ketone (PAEK-C) resin, at high strain rate, the dynamic compression and tensile experiments were carried out on a modified split Hopkinson pressure bar (SHPB) and high speed material apparatus, respectively. Stress-strain curves of the epoxy resin matrix composites were obtained and analyzed. Damage mechanism under high strain rate was characterized through the scanning electron microscope (SEM) observation. Results of the dynamic compression tests indicated that, although the effects of strain rate remarkably influenced the variations in stress, the behaviors of the epoxy resin matrix played a more significant role than strain rate in the determination of the high strain rate. It was reflected through increased ductility of the samples and reduced slope of the stress-strain curves. The dynamic impact tensile tests results show that, PAEK-C fillers exhibited dramatic toughening effect. The increase of the volume fraction of PAEK-C rich phase inevitably forces the crack to overcome more tearing deformation of PAEK-C rich phase. At the same time, the enhancement of plastic capacity may also induce a larger range of cooperative deformation at the crack tip. [ABSTRACT FROM AUTHOR]

CD34, cytokeratin (CK) 19, cytokeratin (CK) 20, and Ki67 have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD34, CK19, CK20, and Ki67 expressions in colorectal cancer (CRC) and to evaluate their involvement in the progression of CRC. CD34, CK19, CK20, and Ki67 expressions were assessed in paraffin-embedded specimens collected from 152 cases of CRC and 30 paired normal colorectal tissues by immunohistochemistry. The relationships between CD34, CK19, CK20, and Ki67 expressions and CRC were evaluated. The association of CD34 and Ki67 protein expressions with the clinicopathological characteristics and the prognosis of CRC were subsequently assessed. CD34, CK19, CK20, and Ki67 expressed highly in CRC tissues relative to normal colorectal tissues. Using immunostaining scoring, a significant correlation of CD34 and Ki67 with the UICC staging and histo-differentiation of CRC was found (P < 0.05), but no such correlation of CK19 and CK20 with the UICC staging and histo-differentiation (P > 0.05). Meanwhile, no relationship of CD34, CK19, CK20, and Ki67 with the location of CRC was found (P > 0.05). Patients with high expressions of CD34 and Ki67 had the lowest survival (P < 0.05). The results suggest that concurrent expression of CD34 and Ki67 may be an important characteristic of CRC which may help in the prediction of CRC progression. [ABSTRACT FROM AUTHOR]

A new sulfonyl fluoride reagent 1-bromobut-3-ene-1,3-disulfonyl difluoride (BEDF) was developed. This unique reagent possesses two clickable functionalities to be used for both azide-alkyne cycloaddition click and SuFEx click reactions. This new reagent was applied for the regioselective construction of a class of novel triazolyl vinyl sulfonyl fluorides in which the C-4 position 1 H -1,2,3-triazoles were functionalized with vinyl sulfonyl fluorides of exclusively E -configuration.

Herein, we developed a practical method for synthesizing a class of novel and highly valuable indolyl vinyl sulfonyl fluorides. This protocol has carved out a path for constructing a broad range of vinyl sulfonyl fluorinated indoles with exclusive stereo- and regioselectivity through the Friedel-Crafts/elimination reaction without any transition-metal catalyst. This transformation features mild conditions, high efficiency, excellent selectivity, and rich substrate compatibility, highlighting its significant value in medicinal chemistry and many related disciplines.

Purpose: To develop a CT radiomics model to predict pathological complete response (pCR) of advanced esophageal squamous cell carcinoma (ESCC) toneoadjuvant chemotherapy using paclitaxel and cisplatin., Materials and Methods: 326 consecutive patients with advanced ESCC from two hospitals undergoing baseline contrast-enhanced CT followed by neoadjuvant chemotherapy using paclitaxel and cisplatin were enrolled, including 115 patients achieving pCR and 211 patients without pCR. Of the 271 cases from 1st hospital, 188 and 83 cases were randomly allocated to the training and test cohorts, respectively. The 55 patients from a second hospital were assigned as an external validation cohort. Region of interest was segmented on the baseline thoracic contrast-enhanced CT. Useful radiomics features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomics features were chosen using support vector machine (SVM). Discriminating performance was assessed with area under the receiver operating characteristic curve (ROC) and F-1score. The calibration curves and Brier score were used to evaluate the predictive accuracy., Results: Eight radiomics features were selected to create radiomics models related to pCR of advanced ESCC (P-values < 0.01 for both the training and test cohorts). SVM model showed the best performance (AUCs = 0.929, 0.868 and 0.866, F-1scores = 0.857, 0.847 and 0.737 in the training, test and external validation cohorts, respectively). The calibration curves and Brier scores indicated goodness-of-fit and its great predictive accuracy., Conclusion: CT radiomics models could well help predict pCR of advanced ESCC, and SVM model could be a suitable predictive model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A practical copper-catalyzed process for the synthesis of the β-arylethenesulfonyl fluorides is described. A series of α-bromo arylethyl sulfonyl fluorides was prepared via Meerwein reaction from arenediazonium tetrafluoroborates and ethenesulfonyl fluoride (ESF) under mild conditions. The following β-arylethenesulfonyl fluorides were further obtained through a β-elimination reaction. This protocol features excellent regio- and stereoselectivity and broad substrate scope.

A practical and efficient method for the C-3 site selective alkenylation of indoles was developed for constructing novel indole-functionalized vinyl sulfonyl fluorides and indolyl allylic sulfonyl fluorides. The reaction is accomplished with exclusive regio- and stereoselectivity without using transition metal catalysts, providing novel products of great potential value in medicinal chemistry, chemical biology, and drug discovery.

In this paper, the hydrogenation of aldehydes and ketones using the RANEY® nickel catalyst was successfully applied for the synthesis of alcohol compounds without additional column chromatographic purification. This synthetic strategy features a wide range of substrates, excellent atom economy, high chemical discrimination and the use of a ligand-free catalytic system. Reactions were performed at room temperature in water providing alcohols in high yields and purity.

The construction of a class of novel triazole molecules containing sulfonyl fluoride functionalities was achieved through Cu-catalyzed click chemistry in good to excellent yields. The sulfonyl fluoride moieties were cleaved completely under base conditions to produce N -unsubstituted triazoles quantitatively, which provides a strategy to combine SuFEx click chemistry with Cu-catalyzed click chemistry ingeniously., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A one-pot, sequential three-component reaction between salicylaldehyde, indole, and 2-bromoprop-2-ene-1-sulfonyl fluoride (BPESF) has been demonstrated for the synthesis of sulfonyl fluoride substituted 4 H -chromene derivatives in moderate to excellent yields (45%-94%). This one-pot sequential method features easily available starting materials, wide substrate scope, mild conditions, and great efficiency.

Sulphur fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulphur connective hubs. Here, we reported an efficient synthesis and in situ screening method for building a library of sulphonamides on the picomolar scale by SuFEx reaction between a sulphonyl fluoride (RSO 2 F) core and primary or secondary amines. This biocompatible SuFEx reaction would allow us to rapidly synthesise sulphonamide molecules, and evaluate their ChE inhibitory activity. Compound T14-A24 was identified as a reversible, competitive, and selective AChE inhibitor ( K i = 22 nM). The drug-like evaluation showed that T14-A24 had benign BBB penetration, remarkable neuroprotective effect, and safe toxicological profile. In vivo behavioural study showed that T14-A24 treatment improved the Aβ 1 - 42 -induced cognitive impairment, significantly prevented the effects of Aβ 1 - 42 toxicity. Therefore, this SuFEx click reaction can accelerate the discovery of lead compounds.

In the present paper, the dislocation-precipitate interaction in the Inconel 718 superalloy is studied by means of molecular dynamics simulation. The atomistic model composed of the ellipsoidal Ni3Nb precipitate (γ″ phase) and the Ni matrix is constructed, and tensile tests on the composite Ni3Nb@Ni system along different loading directions are simulated. The dislocation propagation behaviors in the precipitate interior and at the surface of the precipitate are characterized. The results indicate that the dislocation shearing and bypassing simultaneously occur during plastic deformation. The contact position of the dislocation on the surface of the precipitate could affect the penetration depth of the dislocation. The maximum obstacle size, allowing for the dislocation shearing on the slip planes, is found to be close to 20 nm. The investigation of anisotropic plastic deformation behavior shows that the composite system under the loading direction along the major axis of the precipitate experiences stronger shear strain localizations than that with the loading direction along the minor axis of the precipitate. The precipitate size effect is quantified, indicating that the larger the precipitate, the lower the elastic limit of the flow stress of the composite system. The dislocation accumulations in the precipitate are also examined with the dislocation densities given on specific slip systems. These findings provide atomistic insights into the mechanical behavior of nickel-based superalloys with nano-precipitates.

SuFEx click chemistry has been a method for the rapid synthesis of functional molecules with desirable properties. Here, we demonstrated a workflow that allows for in situ synthesis of sulfonamide inhibitors based on SuFEx reaction for high-throughput testing of their cholinesterase activity. According to fragment-based drug discovery (FBDD), sulfonyl fluorides [R-SO 2 F] with moderate activity were identified as fragment hits, rapidly diversified into 102 analogs in SuFEx reactions, and the sulfonamides were directly screened to yield drug-like inhibitors with 70-fold higher potency (IC 50  = 94 nM). Moreover, the improved molecule J8-A34 can ameliorate cognitive function in Aβ 1-42 -induced mouse model. Since this SuFEx linkage reaction succeeds on picomole scale for direct screening, this methodology can accelerate the development of robust biological probes and drug candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A SO 2 F 2 -mediated ring-opening cross-coupling of cyclobutanone oxime derivatives with alkenes was developed for the construction of a range of δ-olefin-containing aliphatic nitriles with ( E )-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N-O activation., (Copyright © 2023, Chen and Qin.)

β-lactamases are enzymes that deactivate β-lactam antibiotics through a hydrolysis mechanism. There are two known types of β-lactamases: serine β-lactamases (SBLs) and metallo β-lactamases (MBLs). The two existing strategies to overcome β-lactamase-mediated resistance are (a) to develop novel β-lactam antibiotics that are not susceptible to hydrolysis by these enzymes; or (b) to develop β-lactamase inhibitors that deactivate the enzyme and thereby restore the efficacy of the co-administered antibiotics. Many commercially available SBL inhibitors are used in combination therapy with antibiotics to treat antimicrobial resistant infections; however, there are only a handful of MBL inhibitors undergoing clinical trials. In this study, we present 11 novel potential MBL inhibitors ( via multi-step chemical synthesis), that have shown to completely restore the efficacy of meropenem (≤2 mg L -1 ) against New Delhi metallo-β-lactamase (NDM) producing Klebsiella pneumoniae in vitro . These compounds contain a cyclic amino acid zinc chelator conjugated to various commercially available β-lactam antibiotic scaffolds with the aim to improve the overall drug transport, lipophilicity, and pharmacokinetic/pharmacodynamic properties as compared to the chelator alone. Biological evaluation of compounds 24b and 24c has further highlighted the downstream application of these MBLs, since they are non-toxic at the selected doses. Time-kill assays indicate that compounds 24b and 24c exhibit sterilizing activity towards NDM producing Klebsiella pneumoniae in vitro using minimal concentrations of meropenem. Furthermore, 24b and 24c proved to be promising inhibitors of VIM-2 ( K i = 0.85 and 1.87, respectively). This study has revealed a novel series of β-lactam MBLIs that are potent, efficacious, and safe leads with the potential to develop into therapeutic MBLIs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A green and efficient method for the synthesis of β-sulfonyl aliphatic sulfonyl fluorides was developed. This reaction works in aqueous media under mild and environmentally benign conditions without any ligand or additive. The efficiency of this method is demonstrated by isolating the desired products obtained through simple filtration.

Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Twenty-two quaternary 8-dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol/water partition coefficients by up to values 3-4 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds in vitro. The IC 50 values of antiproliferative activity of quaternary 8-dichloromethyl-pseudoberberine 4-chlorobenzenesulfonate and quaternary 8-dichloromethyl-pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31 μM and 0.41 μM, respectively, significantly stronger than those of other compounds and positive control 5-fluorouracil. These findings suggest that 8-dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Natural QPAs have anti-cancer property. The prodrugs of QPAs synthesized in our work with significantly improved solubility showed significantly stronger activity in animal experiments. Nevertheless, the mechanism of action of QPAs for treating cancers remains poorly understood. Here, a chemoproteomic study reveals that QPAs non-covalently and multivalently bind to PES1 in CRC cells, which impinges on the direct interaction between hTERT and hTR in the assembly of the telomerase complex, downregulates telomerase activity, and so promotes the aging process of CRC cells. This study is beneficial for us to conduct extensively the pharmaceutical chemistry research of QPAs., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

A [3 + 2] cycloaddition reaction of N -aminopyridines, N -aminoquinolines, and N -aminoisoquinolines with 1-bromoethene-1-sulfonyl fluoride (BESF) was performed to obtain optimum yields of various useful pyrazolo[1,5- a ]pyridinyl, pyrazolo[1,5- a ]quinolinyl, and pyrazolo[5,1- a ]isoquinolinyl sulfonyl fluorides (43-90% yield). The transformation process showed broad substrate specificity, mild reaction conditions, and operational simplicity. Therefore, the reaction has great applicable value in the field of medicinal chemistry and other disciplines.

A new sulfonyl fluoride reagent ( E )-2-methoxyethene-1-sulfonyl fluoride (MeO-ESF) was developed and successfully applied for the construction of enaminyl sulfonyl fluoride ( N -ESF). This protocol provides highly atom-economical access to diverse N -ESF and produces CH 3 OH as the sole byproduct under mild and environmentally benign conditions.

Compounds containing an SF bond have garnered intense interest in the chemical and biological literature. In particular, sulfonyl fluorides (RSO 2 F) are commonly used as covalent protein inhibitors and biological probes. The introduction of the fluorine atom into drugs often leads to significantly promoted medicinal properties, which revolutionized the development of pharmaceuticals and gained attention because of the beneficial properties of these small and highly electro-negative halogens. The sulfonyl fluoride functional group has also been widely adopted throughout the field of chemical biology due to its unique balance between reactivity and stability under physiological conditions. This comprehensive review highlights the recent developments of sulfonyl fluorides based compounds in a massive range of therapeutic applications. We believe this review article will be helpful to inspire new ideas for structural design and developments of less toxic and potent Sulfur based drugs against the numerous death-causing diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Arterial remodeling is a common pathological basis of cardiovascular diseases such as atherosclerosis, vascular restenosis, hypertension, pulmonary hypertension, aortic dissection, and aneurysm. Vascular smooth muscle cells (VSMCs) are not only the main cellular components in the middle layer of the arterial wall but also the main cells involved in arterial remodeling. Dedifferentiated VSMCs lose their contractile properties and are converted to a synthetic, secretory, proliferative, and migratory phenotype, playing key roles in the pathogenesis of arterial remodeling. As mitochondria are the main site of biological oxidation and energy transformation in eukaryotic cells, mitochondrial numbers and function are very important in maintaining the metabolic processes in VSMCs. Mitochondrial dysfunction and oxidative stress are novel triggers of the phenotypic transformation of VSMCs, leading to the onset and development of arterial remodeling. Therefore, pharmacological measures that alleviate mitochondrial dysfunction reverse arterial remodeling by ameliorating VSMCs metabolic dysfunction and phenotypic transformation, providing new options for the treatment of cardiovascular diseases related to arterial remodeling. This review summarizes the relationship between mitochondrial dysfunction and cardiovascular diseases associated with arterial remodeling and then discusses the potential mechanism by which mitochondrial dysfunction participates in pathological arterial remodeling. Furthermore, maintaining or improving mitochondrial function may be a new intervention strategy to prevent the progression of arterial remodeling.

A series of compact and multifunctional 2-alkyl-substituted vinyl sulfonyl fluorides were efficiently prepared from the corresponding alkyl iodides and 2-chloroprop-2-ene-1-sulfonyl fluoride (CESF). This Giese-type radical approach provided new and general access to alkenyl sulfonyl fluorides, including structures that would otherwise be challenging to synthesize with previously established methods. A correspondingly large collection of derivatization reactions was also demonstrated on the alkenyl sulfonyl fluorides.

Novel scaffolds are expected to treat Alzheimer's disease, pyrazole-5-fluorosulfates were found as selective BuChE inhibitors. Compounds K1-K26 were assayed for ChE inhibitory activity, amongst them, compound K3 showed potent BuChE and h BuChE inhibition (IC 50 = 0.79 μM and 6.59 μM). SAR analysis showed that 1-, 3-, 4-subtituent and 5-fluorosulfate of pyrazole ring affected BuChE inhibitory activity. Molecular docking showed that the fluorosulfate increased the binding affinity of h BuChE through π-sulphur interaction. Compound K3 was a reversible, mixed and non-competitive BuChE inhibitor ( K i = 0.77 μM) and showed remarkable neuroprotection, safe toxicological profile and BBB penetration. In vivo behavioural study showed that K3 treatment improved the A β 1 - 42 -induced cognitive impairment, and significantly prevented the effects of A β 1 - 42 toxicity. Therefore, selective BuChE inhibitor K3 has potential to be further developed as AD therapeutics.

A method for the mild and efficient synthesis of 1,3-dienylsulfonyl fluorides was developed via dehalogenation of α-halo-1,3-dienylsulfonyl fluorides in the presence of zinc powder and acetic acid, achieving exclusive chemo- and stereoselectivities. This protocol was successfully applied to the synthesis of heterocyclic dienylsulfonyl fluorides and polyene sulfonyl fluoride.

Background: Endometrial cancer is associated with a high mortality rate, which warrants the identification of novel diagnostic markers and therapeutic targets. The aim of this study is to evaluate the role of SNORD15B in the development of endometrial cancer and explore the potential underlying mechanisms., Methods: Bioinformatics was used to analyze the expression level and prognostic relevance of SNORD15B in endometrial cancer. The Ishikawa and HEC-1B cells were respectively transfected with SNORD15B expression plasmid and an antisense oligonucleotide, or the corresponding empty vector and a nonspecific sequence. The malignant phenotype of the suitably transfected cells was assessed by standard in vitro functional assays and the establishment of in vivo xenografts. The expression levels of the specific markers were analyzed with RT-qPCR and western blotting. The subcellular localization of P53 was determined by analyzing the nuclear and cytoplasmic fractions. RIP, Co-IP, and immunohistochemistry were performed as per standard protocols., Results: SNORD15B was overexpressed in the endometrial cancer tissues and correlated to a poor prognosis. Ectopic expression of SNORD15B in Ishikawa cells inhibited apoptosis, increased the proliferation, invasion, and migration in vitro , and enhanced their tumorigenicity in vivo . SNORD15B overexpression also upregulated TRIM25 and accelerated P53 accumulation in the cytoplasm of the endometrial cancer cells., Conclusion: SNORD15B functions as an oncogene in endometrial cancer by targeting the TRIM25/P53 complex and blocking the nuclear translocation of P53., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jing-tao Wen et al.)

In the past ten years, the clinical application of fecal microbiota transplantation (FMT) in the treatment of intestinal and extraintestinal diseases has attracted much attention. In China, there are more than 300 hospitals that have developed FMT, but the development of FMT is still in its early stage. The clinical practice of FMT needs to form a standardized system, including management of donors and acceptors, preparation of capsules containing certain gut bacteria, evaluation of effectiveness, and study of fecal microbiota and disease. In order to promote the establishment of the standard system of FMT and the healthy development of FMT, this paper expounds the establishment of the standardization of domestic flora transplantation according to the relevant literature, as well as the experience of 10000 cases and 95300 times of FMT in our center.

With the development of global economy and society,the number of patients who suffer from functional gastrointestinal disorders (FGID) and mental illness is growing. In recent years, a substantial amount of high-quality research evidence shows that these two kinds of diseases often coexist, and they are mutually causal, and their common pathophysiology is the abnormal interaction of "bacteria-gut-brain axis". In clinical practice, there are some problems, such as insufficient recognition and attention of both doctors and patients to its clinical manifestations, lack of understanding of pathophysiological mechanism, and lack of overall and integrated views of intervention methods, which may be the main factors of poor curative effect at present. Therefore, according to the global research progress and the author's clinical experience, we put forward a new viewpoint of "gastrointestinal psychiatry", it concluded that clinical intervention strategies needed to include dietary and lifestyle changes as well as multidisciplinary interventions such as probiotics, prebiotic, fecal microbiota transplantation and cognitive psychology. On the basis of gastrointestinal psychiatry, this paper systematically elaborated the diagnosis and treatment of this kind of diseases.

Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m 2 ); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month ( P <0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month ( P <0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg ( P <0.001), and BMI had increased from 15.17±1.87 kg/m 2 to 19.58±1.42 kg/m 2 ( P <0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L ( F =2.715, P =0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months ( F =15.124, P <0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months ( P <0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months ( P <0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months ( P <0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months ( P <0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".

Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10 8 /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10 6 /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t =-19.097, P =0.001] and had a lower body mass index [(19.7±0.5) kg/m 2 vs. (20.8±1.3) kg/m 2 , t =-8.726, P =0.001], more in the living bacteria amount in powder [(7.47±1.52)×10 6 /g vs. (5.03±1.38)×10 6 /g, t =11.331, P =0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t =10.415, P =0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t =19.465, P =0.001). The differences were statistically significant (all P <0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P >0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P <0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.

A highly efficient regio- and stereoselective Heck-Matsuda method was developed employing aryl diazoniums and allylsulfonyl fluorides for the construction of a class of novel γ-aryl allylsulfonyl fluorides in the presence of Pd(OAc) 2 and PPh 3 . The method features excellent regio- and stereoselectivity (up to 100% E -selectivity), broad substrate scope and mild reaction conditions. Further application of γ-aryl allylsulfonyl fluoride in SuFEx reactions was achieved to provide their corresponding sulfonates and sulfonamides in excellent yields., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A convenient protocol for the exclusively regio- and stereoselective installation of a bromine atom on the 2-arylvinylsulfonyl fluorides using lithium bromide (LiBr) as the bromine source was described, providing ( Z )-1-bromo-2-arylethene-1-sulfonyl fluorides ( Z -BASF) with versatile reactive handles (bromide, vinyl, and sulfonyl fluoride) in ≤88% yield. Meanwhile, Z -BASF molecules displayed various reactivities in a series of chemical transformations.

A copper-catalyzed cascade reaction of α-diazocarbonyl compounds with ethenesulfonyl fluoride (ESF) is developed, affording a variety of highly functionalized pyrazolyl aliphatic sulfonyl fluorides in good to excellent yields (66-98%). This transformation features broad substrates, exclusive regioselectivity, high atom economy and operational simplicity, thus providing a straightforward method for the direct construction of pyrazole-containing aliphatic sulfonyl fluorides, which will provide great applicable value in medicinal chemistry and other related disciplines.

In order to obtain new dihydrocoptisine-type compounds with stable structure and activating XBP1 transcriptional activity, (±)-8-trifluoromethyldihydrocoptisine derivatives as target compounds were synthesized from quaternary ammonium chlorides of coptisine alkaloids as starting materials by a one-step reaction. The structures of the synthesized compounds were confirmed by 1 H-, 13 C-, and 19 F-NMR as well as HRESIMS methods. These compounds showed more significant structural stability and activating XBP1 transcription activity in vitro than dihydrocoptisine as positive control. No obvious cytotoxicity on normal cell in vitro was observed with (±)-8-trifluoromethyldihydrocoptisines. Trifluoromethylation can be used as one of the fluorine modification strategies for dihydrocoptisines to guide follow-up studies on structural modification of coptisine-type alkaloids and on anti-Ulcerative colitis drugs with coptisines.

The first total synthesis of ( S )-(+)-ovigerine, ( S )-(+)- N -formylovigerine, and (6a S ,6a' S )-(+)-ovigeridimerine of aporphine alkaloids with a benzo[ d ][1,3]dioxole structure feature was established. The strategy was based upon the well-known Pd-catalyzed arylation to set the aporphine framework, and Noyori asymmetric hydrogenation followed by diastereoselective resolution to achieve excellent enantioselectivity. By slightly modifying the total synthetic route and strategically combining it with a aza-Michael addition, Bischler-Napieralski reaction and N -arylation, this methodology was also applied to the total syntheses of benzo[ d ][1,3]dioxole-type benzylisoquinoline alkaloids of coptisines and dibenzopyrrocolines, including two impatiens, tetrahydrocoptisine, and quaternary coptisine bromide of coptisines and two dibenzopyrrocoline analogues, with the syntheses of all of these target compounds being efficient. Among the nine synthesized compounds, the total syntheses of the three aporphines and the two impatiens, all with ee values of greater than 99%, were reported for the first time. This work also represents the first unification of synthetic routes for the total synthesis of benzo[ d ][1,3]dioxole-type aporphines, coptisines, and dibenzopyrrocolines.

A large number of small non-coding RNAs derived from tRNAs, called tRNA-derived small RNA (tsRNAs), have been identified by high-throughput RNA sequencing of cell lines. Further research has revealed that they are not produced via random tRNA degradation, but through degradation by specific nuclease cleavages, such as Elac Ribonuclease Z 2 (ELAC2)/RNase Z, RNase L, Dicer, and angiogenin (ANG), the tsRNAs can be classified into the following types based on the location from which they have been derived from the parental tRNA: tRF-1s, tRF-3s, tRF-5s, tiRNA, and tRF-2s/i-tRFs. Moreover, tsRNAs are a type of small RNAs with diverse functions, including gene expression regulation, anti-apoptosis, translation inhibition, participation in epigenetic regulation, initial virus reverse transcription, promote virus replication and cell-to-cell communication. Certain types of tsRNAs are overexpressed in cancer tissues, but are underexpressed in normal tissues. Therefore, the relationship between tsRNAs and the occurrence and development of cancer has attracted significant research attention. Research advancements have contributed to further discoveries of the biological activities of tsRNAs, but the mechanisms of their biogenesis and functions have not been fully elucidated. This article reviews the classification and biological functions of tsRNAs, and introduces the research progress in gynecological malignancies., (© 2021. The Author(s).)

To discover novel scaffolds as leads against dementia, a series of δ-aryl-1,3-dienesulfonyl fluorides with α-halo, α-aryl and α-alkynyl were assayed for ChE inhibitory activity, in which compound A10 was identified as a selective BuChE inhibitor (IC 50 = 0.021 μM for eqBChE, 3.62 μM for hBuChE). SAR of BuChE inhibition showed: (i) o - > m - > p -; -OCH 3 > -CH 3 > -Cl (-Br) for δ -aryl; (ii) α-Br > α-Cl, α-I. Compound A10 exhibited neuroprotective, BBB penetration, mixed competitive inhibitory effect on BuChE ( K i = 29 nM), and benign neural and hepatic safety. Treatment with A10 could almost entirely recover the A β 1-42 -induced cognitive dysfunction to the normal level, and the assessment of total amount of A β 1-42 confirmed its anti-amyloidogenic profile. Therefore, the potential BuChE inhibitor A10 is a promising effective lead for the treatment of AD.

Novel pyridine-containing sultones were synthesized and evaluated for their cholinesterase (ChE) inhibitory activity. Most of compounds showed selective acetylcholinesterase (AChE) inhibitory activity. The structure-activity relationship (SAR) showed: (i) the fused pyridine-containing sultones increase AChE inhibition, series B>series A; (ii) for series A, the effect of the 4-substituent on AChE activity, p->m- or o-; (iii) for series B, a halophenyl group increase activity. Compound B4 (4-(4-chlorophenyl)-2,2-dioxide-3,4,5,6-tetrahydro-1,2-oxathiino[5,6-h]quinoline) was identified as a selective AChE inhibitor (IC 50 =8.93 μM), and molecular docking studies revealed a good fit into TcAChE via hydrogen interactions between the δ-pyridylsultone scaffold with Asp72, Ser122, Phe288, Phe290 and Trp84. Compound B4 showed reversible and non-competitive (K i =7.67 μM) AChE inhibition, nontoxicity and neuroprotective activity. In vivo studies confirmed that compound B4 could ameliorate the cognitive performance of scopolamine-treated C57BL/6 J mice, suggesting a significant benefit of AChE inhibition for a disease-modifying treatment of AD., (© 2021 Wiley-VCH GmbH.)

A CuO-promoted direct hydrocarboxylation of ethenesulfonyl fluoride (ESF) was developed using carboxylic acid as a nucleophile under mild conditions. A variety of molecules containing both ester group and aliphatic sulfonyl fluoride moiety exhibit great potential in medicinal chemistry and chemical biology. Furthermore, the modification of the known drugs Ibuprofen and Aspirin was also demonstrated., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Epilepsy is a clinical syndrome caused by the highly synchronized abnormal discharge of brain neurons. It has the characteristics of paroxysmal, transient, repetitive, and stereotyped. Circular RNAs (circRNAs) are a recently discovered type of noncoding RNA with diverse cellular functions related to their excellent stability; additionally, some circRNAs can bind and regulate microRNAs (miRNAs). The present study was designed to screen the differentially expressed circRNA in an acute seizure model of epilepsy in mice, analyze the related miRNA and mRNA, and study their participating functions and enrichment pathways. In order to obtain the differential expression of circRNA in epilepsy and infer their function, we used next-generation sequencing and found significantly different transcripts. CIRI (circRNA identifier) software was used to predict circRNA from the hippocampus cDNA, EdgeR was applied for the differential circRNA analysis between samples, and Cytoscape 3.7.2 software was used to draw the network diagram. A total of 10,388 differentially expressed circRNAs were identified, of which 34 were upregulated and 66 were downregulated. Among them, mm9&#95;circ&#95;008777 and mm9&#95;circ&#95;004424 were the key upregulated genes, and their expression in the epilepsy group was verified using Quantitative real-time PCR (QPCR). The analysis indicated that the extracted gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were closely related to several epilepsy-associated processes. This study determined that mm9&#95;circ&#95;008777 and mm9&#95;circ&#95;004424 are potential biomarkers of epilepsy, which play important roles in epilepsy-related pathways. These results could help improve the understanding of the biological mechanisms of circRNAs and epilepsy treatments., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Background: Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy., Methods: Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin-tazobactam) for 1 week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1 week. The PAA group received antibiotic treatment for 1 week followed by probiotics for 1 week. Fecal samples were collected at four time nodes: newborn, 1 week, 2 weeks, and 42 days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons., Results: Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium., Conclusions: These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits., (© 2021. Children's Hospital, Zhejiang University School of Medicine.)

Both cis and trans relative configurations of functionalized cyano cyclopropane bearing sulfonyl fluoride moiety were accessed by Corey-Chaykovsky cyclopropanation reactions. This protocol used mild conditions, and obtained good yields with excellent functional group compatibility. Further application of this class of compounds in SuFEx reactions and cyano reductions were also successfully achieved in good yields.

Destabilizing and reprogramming regulatory T (Treg) cells have become a potential strategy to treat tumor. Mounting evidence indicates that the transcription factor Helios is required for the stable differentiation of Treg lineage. Hence, we investigated whether Helios suppression could be a potential treatment option for pancreatic cancer patients. We found that Helios + cells were predominantly in Foxp3 + Treg cells. By contrast, Foxp3 + Treg cells can be Helios + or Helios - , but the level of Foxp3 expression was significantly higher in Helios + Foxp3 + Treg cells than in Helios - Foxp3 + Treg cells. Resected pancreatic tumors were highly enriched with both Helios + Foxp3 + Treg cells and Helios - Foxp3 + Treg cells. Also, the proportion of Helios + cells in total Foxp3 + Treg cells was significantly higher in peripheral blood mononuclear cells (PBMCs) of patients than in PBMCs of healthy controls and further increased in patient tumors. Using shRNA, we knocked down Helios expression without significant downregulation of Foxp3. After Helios knockdown, CD4 + CD25 + CD127 - Treg cells presented significantly lower levels of TGF-β secretion, lower levels of IL-10 secretion, and higher levels of IFN-γ secretion. In addition, Helios shRNA-transfected CD4 + CD25 + CD127 - Treg cells presented lower capacity to inhibit CD4 + CD25 - CD127 + T conventional cell proliferation than control shRNA-transfected CD4 + CD25 + CD127 - Treg cells. Of note, CD4 + CD25 + CD127 - Treg cells from pancreatic cancer patients demonstrated higher TGF-β expression and higher suppression capacity than the cells from healthy controls. Overall, these results suggest that in pancreatic cancer patients, Helios may serve as a candidate to suppress Treg function, which could be used as a target to treat pancreatic cancer.

Warming strongly stimulates soil nitrous oxide (N 2 O) emission, contributing to the global warming trend. Submerged paddy soils exhibit huge N 2 O emission potential; however, the N 2 O emission pathway and underlying mechanisms for warming are not clearly understood. We conducted an incubation experiment using 15 N to investigate the dynamics of N 2 O emission at controlled temperatures (5, 15, 25, and 35°C) in 125% water-filled pore space. The community structures of nitrifiers and denitrifiers were determined via high-throughput sequencing of functional genes. Our results showed that elevated temperature sharply enhanced soil N 2 O emission from submerged paddy soil. Denitrification was the main contributor, accounting for more than 90% of total N 2 O emission at all treatment temperatures. N 2 O flux was coordinatively regulated by nirK- , nirS- , and nosZ -containing denitrifiers but not ammonia-oxidizing archaea or ammonia-oxidizing bacteria. The nirS -containing denitrifiers were more sensitive to temperature shifts, especially at a lower temperature range (5 to 25°C), and showed a stronger correlation with N 2 O flux than that of nirK -containing denitrifiers. In contrast, nosZ -containing denitrifiers exhibited substantial variation at higher temperatures (15 to 35°C), thereby playing an important role in N 2 O consumption. Certain taxa of nirS - and nosZ -containing denitrifiers regulated N 2 O flux, including nirS -containing denitrifiers affiliated with Rhodanobacter and Cupriavidus as well as nosZ -containing denitrifiers affiliated with Azoarcus and Azospirillum . Together, these findings suggest that elevated temperature can significantly increase N 2 O emission from denitrification in submerged paddy soils by shifting the overall community structures and enriching some indigenous taxa of nirS - and nosZ -containing denitrifiers. IMPORTANCE The interdependence between global warming and greenhouse gas N 2 O has always been the hot spot. However, information on factors contributing to N 2 O and temperature-dependent community structure changes is scarce. This study demonstrated high-temperature-induced N 2 O emission from submerged paddy soils, mainly via stimulating denitrification. Further, we speculate that key functional denitrifiers drive N 2 O emission. This study showed that denitrifiers were more sensitive to temperature rise than nitrifiers, and the temperature sensitivity differed among denitrifier communities. N 2 O-consuming denitrifiers ( nosZ -containing denitrifiers) were more sensitive at a higher temperature range than N 2 O-producing denitrifiers ( nirS -containing denitrifiers). This study's findings help predict N 2 O fluxes under different degrees of warming and develop strategies to mitigate N 2 O emissions from paddy fields based on microbial community regulation.

Trichoptera are a group of the benthic organism, almost all of which live in water during their life cycle. Trichoptera usually develop through egg, larva, pupa, and moth stages. In its larval stage, Trichoptera usually live in water and are often called the caddisfly. In this study, the mitochondrial genome of Macrostemum floridum was analyzed. The total length of the mitochondrial genome is 15,424 bp and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and one control region. The genome has a typical mitochondrial gene sequence of Trichoptera. Phylogenetic analysis of the mitochondrial genomes of 23 species of Trichoptera and Lepidoptera showed that M. floridum forms a monophyletic group with other species of Lepidoptera., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)