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An ionic cascade insertion/cyclization reaction of thia-/selena-functionalized arylisocyanides has been successfully developed for the efficient and practical synthesis of 2-halobenzothiazole/benzoselenazole derivatives. This synthetic protocol, incorporating a halogen atom when forming the five-membered ring of benzothia/selenazoles, is different from the existing ones, where halogenation of the preformed benzothia/selenazole precursors happens. Additionally, a facile access to 2-aminobenzothiazoles is also achieved by the one-pot cascade reaction of 2-isocyanoaryl thioethers, iodine, and amines.

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.

Circular RNAs (circRNAs) have a critical regulatory function in human glioma. However, novel circRNAs related to different pathological grades of glioma and their crucial potential function are worth screening and prediction. CircRNA expression profiling was performed for 6 paired high- and low-grade glioma tissues and 5 adjacent normal brain tissues through next-generation sequencing. Quantitative real-time PCR (qRT-PCR) was conducted to validate circRNA expression. Bioinformatics analysis was performed, and circRNA-miRNA-mRNA networks were constructed. The expression and survival data of miRNAs and target genes were examined by GEPIA, Chinese Glioma Genome Atlas (CGGA), ONCOMINE, and cBioPortal databases. The RNA binding proteins (RBPs), open reading frames (ORFs) and N6-methyladenosine (m6A) modifications of the identified circRNAs were also predicted. Through multilevel research screening, 4 circRNAs (hsa_circ_0000915, hsa_circ_0127664, hsa_circ_0008362, and hsa_circ_0001467) were associated with glioma of different pathological grades and could be preferred candidates for subsequent functional analysis. Therefore, circRNAs are associated with the different pathological grades of glioma and reveal their potential critical regulatory function. CircRNAs might provide vital molecular biomarkers and potential therapeutic targets for glioma.

Long noncoding RNAs (lncRNAs) play an important regulatory role in various diseases. However, the role of lncRNAs in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIPC) is still unknown. The lncRNA profile of rat cortical astrocytes pretreated with ischemic preconditioning was analyzed by high-throughput sequencing. The results of Cell-Counting Kit-8 (CCK-8) assay showed that a novel lncRNA, NONRATT009133.2, which we referred to as brain ischemia–related factor (BIRF), was highly correlated with BIT. Through bioinformatics analysis, we predicted that BIRF, miR-330-5p, and GLT-1 (also named Slc1a2) might constitute a ceRNA regulatory network in the induction of BIT. We found that BIRF was upregulated by CIPC, which promoted GLT-1 expression and BIT induction. BIRF could directly bind to miR-330-5p. Furthermore, miR-330-5p directly targeted GLT-1, and miR-330-5p inhibited both GLT-1 expression and BIT induction in vitro and in vivo. Moreover, BIRF acts as a molecular sponge to competitively bind to miR-330-5p with GLT-1 mRNA, while the miR-330-5p inhibitor reversed all the effects of BIRF siRNA on GLT-1 expression and neuronal vitality. Taken together, our results demonstrate the important roles of the BIRF/miR-330-5p/GLT-1 axis in the induction of BIT by CIPC. BIRF may be a potentially effective therapeutic strategy against stroke injury.

This study is to identify the differentially expressed miRNAs in testicular tissues of rats with hyperuricaemia-induced male infertility. We found that the hyperuricaemia model group had significantly increased serum uric acid, while significantly decreased sperm concentration and motile sperm percentage than normal group (p < .05). A total of 39 differentially expressed miRNAs were identified in the testicular tissues of hyperuricaemia rats compared with the control rats, ten of which were validated by real-time PCR. The target mRNAs of 7 differentially expressed miRNAs (miR-10b-5p, miR-26a-5p, miR-136-5p, miR-151-3p, miR-183-5p, miR-362-3p and miR-509-5p) from 3'-untranslated region binding perspective were enriched in signalling pathways of Wnt, Jak-STAT, mTOR and MAPK. The target mRNAs of 6 differentially expressed miRNAs (miR-136-5p, miR-144-3p, miR-99a-5p, miR-509-5p, miR-451-5p and miR-362-3p) from coding sequence binding perspective were enriched in signalling pathways of Calcium, Notch and MAPK. The functions of miRNAs in testicular tissues of rats with hyperuricaemia were revealed by the differentially expressed miRNAs (miR-183-5p, miR-99a-5p, miR-10b-5p, miR-151-3p, miR-26a-5p, miR-451-5p, miR-362-3p, miR-136-5p, miR-144-3p and miR-509-5p)-mRNAs interaction network. The differentially expressed miRNAs in the testicular tissues of hyperuricaemia rats might shed light on the mechanism of hyperuricaemia-induced male infertility.

Wheat pre-harvest sprouting (PHS) causes serious losses in wheat yield. In this study, precise mapping was carried out in the chromosome segment substitution lines (CSSL) F2 population generated by a direct cross of Zhoumai 18 (PHS-sensitive) and Aegilops tauschii accession T093 (highly PHS-resistant). Three Ae. tauschii-derived quantitative trait loci (QTLs), QDor.3D.1, QDor.3D.2, and QDor.3D.3, were detected on chromosome 3DL using four simple sequence repeats (SSR) markers and 10 developed Kompetitive allele-specific PCR (KASP) markers. Alongside these QTL results, the RNA-Seq and qRT-PCR analysis revealed expression levels of TraesCS3D01G466100 in the QDor.3D.2 region that were significantly higher in CSSLs 495 than in Zhoumai 18 during the seed imbibition treatment. The cDNA sequencing results of TraesCS3D01G466100 showed two single nucleotide polymorphisms (SNPs), resulting in two changed amino acid substitutions between Zhoumai 18 and line 495, and the 148 nt amino acid substitution of TraesCS3D01G466100, derived from Ae. tauschii T093, which may play an important role in the functioning of ubiquitin ligase enzymes 3 (E3) according to the homology protein analysis, which could lead to differential PHS-resistance phenotypes. Taken together, our results may foster a better understanding of the mechanism of PHS resistance and are potentially valuable for marker-assisted selection in practical wheat breeding efforts.

Podocyte injury is the main cause of proteinuria in lupus nephritis (LN). Nestin, an important cytoskeleton protein, is expressed stably in podocytes and is associated with podocyte injury. However, the role of nestin in the pathogenesis of proteinuria in LN remains unclear. The correlations among nestin, nephrin and proteinuria were analyzed in LN patients and MRL/lpr lupus-prone mice. The expression of nestin in mouse podocyte lines (MPCs) and MRL/lpr mice was knocked down to determine the role of nestin in podocyte injury. Inhibitors and RNAi method were used to explore the role of mitophagy and oxidative stress in nestin protection of podocyte from damage. There was a significantly negative correlation between nestin and proteinuria both in LN patients and MRL/lpr mice, whereas the expression of nephrin was positively correlated with nestin. Knockdown of nestin resulted in not only the decrease of nephrin, p-nephrin (Y1217) and mitophagy-associated proteins in cultured podocytes and the podocytes of MRL/lpr mice, but also mitochondrial dysfunction in podocytes stimulated with LN plasma. The expression and phosphorylation of nephrin was significantly decreased by reducing the level of mitophagy or production of reactive oxygen species (ROS) in cultured podocytes. Our findings suggested that nestin regulated the expression of nephrin through mitophagy and oxidative stress to protect the podocytes from injury in LN.

An efficient method for introducing nucleophiles on furan and thiophene has been established via the in situ formation of benzyl-type carbocation, delocalization of the carbocation on heterocyclic ring, and nucleophilic trap of α-EWG ketene S , S -acetal sequence at the 5-position.

A novel catalytic alkylation of indoles with allylic alcohols has been developed. Catalyzed by sulfuric acid (10 mol-%), the reaction between indoles 2 and allylic alcohols 1 based on ketene dithioacetal affords polyfunctionalized indoles 3 in good to excellent yields with high regioselectivities under mild conditions. The catalytic carbon-carbon coupling reaction provides a facile method for the environmentally benign functionalization of indoles with the advantages of good regiochemistry, atom efficiency, easily available catalyst, good yields and the synthetic potential of the polyfunctionalized indole products. Thus, further transformation of the resulting indoles 3 into pyridoindolone derivatives 4 was investigated. The efficiency of this carbon-carbon coupling reaction of 1 with 2 under the catalysis of sulfuric acid is due to the efficient formation of the reactive intermediate I, which is a carbocation that is strongly stabilized by two alkylthio groups at the terminal of the carbon-carbon double bond. The extension of this catalytic strategy to the synthesis of β-naphthols 5 was also achieved.

Due to the laborious and scale-up limitation we have developed a simple system named “root absorption” to express foreign proteins in plants successfully. It has been shown that GFP was expressed in tobacco plants by root absorbing the Agrobacterium suspension containing TMV-based P35S-30B-GFP vector. Various factors influencing the gene expression were studied including Agrobacterium cell density, seedling age, plant materials and inoculation conditions. This system has the special advantages as simple and convenient work process, ease to scale-up and higher level of expression than leaf infiltration. Interestingly, GFP was expressed at 24 h post-absorption. We assume that the root absorption system will facilitate the large-scale production of the recombinant pharmaceutical proteins in plants by means of transient expression.

An easy synthesis of 2,3-di-/1,2,3-trisubstituted indo-l-izines has been developed via a formal [3+2] annulation of α-EWG ketene S, S-acetals with 2-pyridine-/2-quinolinecarbaldehyde. The disubstituted products are formed via an intramolecular aza-Michael- addition and subsequent elimination of acetic acid, followed by desulfenylation- assisted by acetic acid, whereas the trisubstituted products are obtained via a similar conjugate addition followed by elimination of alkanethiol. This strategy has been applied to the synthesis of bis(1-indolizinyl)methanes by the condensation of a 2,3-disubstituted indolizine with aldehydes/ketones in the presence of a catalytic amount of BF 3 ·OEt 2 .

A new family of α-cinnamoyl cyclic ketene dithioacetals (CCKDA) based on a typical donor-π-acceptor structure were designed and synthesized. These unsymmetrical π-conjugated molecules consisted of different electron-donating moiety and the same ketene dithioacetals acceptor. The introduction of different donor moieties changed energy level parameters of the molecules and allowed a fine tuning of their optical and electrical properties. It is promising to apply these compounds in organic light-emitting diodes (OLED) as light-emitting and electron-transporting materials.

An efficient and practical route to α‐aminocarbonylketene dithioacetals 5 and α‐cyanoketene dithioacetals 6 was developed. With readily available α‐acetyl‐α‐aminocarbonyl ketene dithioacetals 4 as the starting materials, α‐aminocarbonylketene dithioacetals 5 were prepared in high yield via base‐catalyzed (sodium hydroxide) deacetylation. In the presence of POCl3 and with DMF as the solvent, α‐cyanoketene dithioacetals 6 were obtained via dehydration of 5 in excellent yield.

A highly efficient BF3.OEt2-catalyzed formal dehydration C-C coupling reaction between readily available alpha-EWG ketene-(S,S)-acetals and various alcohols via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C-C coupling reaction, a series of alkylated alpha-EWG ketene-(S,S)-acetals and functionalized 1,4-pentanedienes were prepared in high to excellent yields and the unsymmetrical biaryls were synthesized in good yields from the generated 1,4-pentanedienes and nitroalkanes through a one-pot annulation-aromatization process.

Mediated by copper acetate, an efficient approach to the C-N bond formation via direct aminolysis of dithioacetals 2 and 5 with ammonia, primary or secondary amines are developed under mild conditions. Enaminones 3 and 6 were thus obtained in high to excellent yields with high chemoselectivity. This type of aminolysis reaction presents a new synthetic application of the dithioacetal functionality. [reaction: see text]

One-pot synthesis of substituted indole N-oxides 3 has been developed based on the TiCl 4 -mediated Baylis-Hillman reaction of α-oxo cyclic ketene-S,S-acetal 1 with o-nitrobenzaldehydes 2 and subsequent intramolecular cyclization reaction.

A series of methyl 3-acetoxy-2-(l,3-dithiolane-2-ylidene)but-3-enoate derivatives has been synthesized by the chemo- and regioselective addition of carboxylic acids to the alkylthio-activated terminal alkynes in moderate to high yields in the absence of catalysts.

Promoted by TiCl4, a series of α-(1,3-dithiolan-2-ylidene)-β-amino carbonyl derivatives––the aza-Morita–Baylis–Hillman adducts, have been synthesized from α-oxo cyclic ketene-S,S-acetals, arylaldehydes, and nitriles in good to excellent yields. A mechanism involving sequential Morita–Baylis–Hillman and Ritter reactions for this novel one-pot, three-component reaction is described.

The first example of TiCl4-mediated Baylis–Hillman type reaction of α-acetyl cyclic ketene dithioacetals with arylaldehydes was described. This methodology adds a new entry to the C–C bond formation at the α-carbon atom of α-oxo ketene dithioacetals.

A facile and efficient one-pot synthesis of 3-[bis(alkylthio/alkylamino)methylene]-5-(pyridyl/quinoylmethyl) furan-2,4(3H,5H)-diones 3 and 10, based on a sequential aldol condensation and lactonization reaction between α-oxo ketene-S,S-acetals 1 and pyridine/qinoline-carboxaldehydes 2 in aqueous media, has been developed. A mechanism involving an acid-catalyzed intramolecular oxa-pyridylethylation reaction is proposed for the formation of the lactone ring.

A one-pot synthesis of substituted pyridines from acyclic ketene-S,S-acetals containing α-acetyl, α-vinyl or α-ethynyl group via the Vilsmeier-Haack reaction has been developed.

The substitution reaction of alkylthio group of α,α′-dioxo ketene dibenzylthioacetals by alkoxy group was performed successfully. This transformation provides a facile route to the useful α,α′-dioxo ketene O,S- and O,O-acetals.

Novel Lewis acid catalyzed reactions of furan and thiophene derivatives including aldehydes and Baylis—Hillman adducts with ketene S,S-acetals are investigated.

A novel catalytic alkylation of indoles with allylic alcohols has been developed. Catalyzed by sulfuric acid (10 mol-%), the reaction between indoles 2 and allylic alcohols 1 based on ketene dithioacetal affords polyfunctionalized indoles 3 in good to excellent yields with high regioselectivities under mild conditions. The catalytic carbon-carbon coupling reaction provides a facile method for the environmentally benign functionalization of indoles with the advantages of good regiochemistry, atom efficiency, easily available catalyst, good yields and the synthetic potential of the polyfunctionalized indole products. Thus, further transformation of the resulting indoles 3 into pyridoindolone derivatives 4 was investigated. The efficiency of this carbon-carbon coupling reaction of 1 with 2 under the catalysis of sulfuric acid is due to the efficient formation of the reactive intermediate I, which is a carbocation that is strongly stabilized by two alkylthio groups at the terminal of the carbon-carbon double bond. The extension of this catalytic strategy to the synthesis of β-naphthols 5 was also achieved.

An easy synthesis of 2,3-di-/1,2,3-trisubstituted indo-l-izines has been developed via a formal [3+2] annulation of α-EWG ketene S, S-acetals with 2-pyridine-/2-quinolinecarbaldehyde. The disubstituted products are formed via an intramolecular aza-Michael- addition and subsequent elimination of acetic acid, followed by desulfenylation- assisted by acetic acid, whereas the trisubstituted products are obtained via a similar conjugate addition followed by elimination of alkanethiol. This strategy has been applied to the synthesis of bis(1-indolizinyl)methanes by the condensation of a 2,3-disubstituted indolizine with aldehydes/ketones in the presence of a catalytic amount of BF 3 ·OEt 2 .

An efficient and practical route to α‐aminocarbonylketene dithioacetals 5 and α‐cyanoketene dithioacetals 6 was developed. With readily available α‐acetyl‐α‐aminocarbonyl ketene dithioacetals 4 as the starting materials, α‐aminocarbonylketene dithioacetals 5 were prepared in high yield via base‐catalyzed (sodium hydroxide) deacetylation. In the presence of POCl3 and with DMF as the solvent, α‐cyanoketene dithioacetals 6 were obtained via dehydration of 5 in excellent yield.

We examined how Newcastle disease virus (NDV) and influenza A virus (IAV) inactivated by 5% formaldehyde, used either alone or in combination, can induce apoptosis in both HeLa and SP2/0 cells. Inactive NDV and IAV demonstrated enhanced rates of lysis in apoptotic tumor cells and greater antitumor effects when combined. Our study supports the argument that viral replication does not cause virally induced apoptosis.

A highly efficient BF3·OEt2-catalyzed formal dehydration C−C coupling reaction between readily available α-EWG ketene-(S,S)-acetals and various alcohols via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C−C coupling reaction, a series of alkylated α-EWG ketene-(S,S)-acetals and functionalized 1,4-pentanedienes were prepared in high to excellent yields and the unsymmetrical biaryls were synthesized in good yields from the generated 1,4-pentanedienes and nitroalkanes through a one-pot annulation−aromatization process.

Titanium tetrachloride promoted Michael addition reactions of α-cyanoketene-S,S-acetals 1 with enones 2 have been developed. The polyfunctionalized 2-[1,3]dithiolan-2-ylidene-3-substituted-5-oxo-5-substituted-pentanenitriles 3 were obtained in good to high yields and the corresponding mechanism was also described.

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.