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The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of β -H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C − X bonds of these products are beneficial for performing further synthetic elaborations. The Mizoroki–Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here the authors present a method to add a heterocycle and transformable halide across a double bond via iridium photocatalysis.

Background Infertility is associated with both physical and psychological challenges, and psychological distress is prevalent among infertility patients. To manage this, they may adopt a range of coping strategies—both adaptive and maladaptive—which can lead to varying outcomes. The choice of strategy will also be affected by many factors. Identifying the strategies and influencing factors of patients in coping with infertility and the infertility treatment process is helpful to help medical staff evaluate the coping effect of patients and give intervention. Methods A qualitative systematic review was conducted to explore the coping strategies and influencing factors of infertility patients in coping with infertility and infertility treatment. Twelve electronic databases were systematically searched: China National Knowledge Infrastructure, Wanfang, VIP, China Biomedical database, PubMed, Web of Science, Embase, Scopus, Proquest (Psychology Database), APA PsycINFO, CINAHL, Cochrane databases, and other resources. Study quality was assessed through The Joanna Briggs Institute’s Qualitative Assessment and Review Instrument by two researchers independently. Data synthesis was conducted using thematic analysis. The study employed the tool named Confidence in the Evidence from Reviews of Qualitative Research to grade the integrated evidence. Results There were 26 qualitative studies included and synthesized into two key themes and 11 sub-themes: (1) Coping strategies: Behavioral coping over verbal expression, blame-oriented coping strategy, developing emotional or psychological defenses, self-management, build inner mental strength, change cognition and behavior, and adopting compromising or adaptive strategies. (2) Influencing factors: individual internal resources, tolerance and rules, comprehensive support systems, and medical uncertainty. Conclusion Infertile patients will use positive and negative strategies to cope with infertility and infertility treatment. Coping strategies are dynamic and evolve over time, and influenced by a variety of personal, social, and clinical factors. Religion, notably, emerged as both a coping mechanism and an influencing factor. It is essential for healthcare professionals to assess coping strategies and their determinants in order. to provide timely and appropriate interventions.

Fluorescent proteins with excitation and emission maxima in the near-infrared would be especially useful because of the low light absorbance of mammalian tissues in this optical window. Verkhusha and colleagues present a bright, photostable fluorescent protein with optimized near-infrared spectra that does not require the addition of exogenous co-factors. Imaging biological processes in mammalian tissues will be facilitated by fluorescent probes with excitation and emission bands within the near-infrared optical window of high transparency 1 . Here we report a phytochrome-based near-infrared fluorescent protein (iRFP) with excitation and emission maxima at 690 nm and 713 nm, respectively. iRFP does not require an exogenous supply of the chromophore biliverdin and has higher effective brightness, intracellular stability and photostability than earlier phytochrome-derived fluorescent probes. Compared with far-red GFP-like proteins, iRFP has a substantially higher signal-to-background ratio in a mouse model due to its infrared-shifted spectra.

Trapa bispinosa Roxb. is a traditional Chinese food which is well known for its medicinal properties. The shell of Trapa bispinosa has anticancer activity, maybe due to its high content of polyphenols. There are few studies on the chemical composition of Trapa bispinosa shells, then we isolated the active components from Trapa bispinosa shell and clarified the mechanism of its anticancer activity. One monomer compound was separated from the ethanol extract of the Trapa bispinosa shell by fractional extraction, silica gel, Sephadex LH-20 gel column chromatography and liquid phase separation. The structure, identified by NMR was 1,2,3,6-tetra-O-galloyl-β-D-glucose. The results of the CCK-8 assay showed that 1,2,3,6-tetra-O-galloyl-β-D-glucose could significantly inhibit the proliferation of gastric cancer SGC7901 cells, and the effect was close to that of 5-fluorouracil. Here, 1,2,3,6-tetra-O-galloyl-β-D-glucose could affect the cell cycle of SGC7901 cells. At the dose of 200 μg/mL and an incubation time of 48 h, SGC7901 cells remained in the G1 phase, apoptosis occurred, the intracellular calcium ion concentration increased and the mitochondrial membrane potential decreased. Transcriptome sequencing analysis showed that the differentially expressed genes were mainly enriched in the P53 signalling pathway associated with apoptosis. The results of qPCR and Western blot showed that 1,2,3,6-tetra-O-galloyl-β-D-glucose could induce apoptosis of SGC7901 cells by up-regulating the expression levels of P21 , PUMA , PERP and IGF-BP3 genes, down-regulating the CyclinD gene, increasing the expression levels of cytochrome C, caspase-3, caspase-9 protein and decreasing that of the protein BCL-2.

Sphingolipids are important signaling molecules for maintaining metabolic and immune homeostasis in the host. These lipids are also produced by gut commensals, most notably by Bacteroides species. Despite the global prevalence of Prevotella copri in gut microbiomes of individuals, little is known about the types of sphingolipids they produce and whether they are similar in composition and structure to those produced by Bacteroides . Given the varied associations of P. copri with diverse sphingolipid-related health outcomes, such as rheumatoid arthritis and glucose intolerance, it is important to first characterize the specific sphingolipids produced by individual strains of P. copri and to identify the genes involved in their pathways of production. This characterization of P. copri -derived sphingolipids provides further insight into how bacterial sphingolipid production can serve as a mechanism for microbial modulation of host phenotypes.

Background Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. Methods A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. Results Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA -related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. Conclusion We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.

Reductive deuteration of N-heterocycles provides an efficient route to deuterated scaffolds, yet achieving controlled deuterium incorporation in quinoline remains challenging. Herein, we report a high-temperature H2-treated Rh/TiO2 catalyst (Rh/TiO2–H500) that enables efficient reductive deuteration of quinoline using D2O as a deuterium source. Structural characterization reveals that reduction at 500 °C induces a pronounced strong metal–support interaction (SMSI), leading to partial TiOx encapsulation of Rh nanoparticles and interfacial electron transfer that generates electron-rich Rh0 species. This optimized interfacial structure promotes cooperative C–H activation and effective H/D transfer across the reduced quinoline framework, affording high deuterium incorporation at multiple positions of 1,2,3,4-tetrahydroquinoline (THQ). These results highlight the importance of SMSI-driven electronic and interfacial modulation in regulating reductive H/D exchange over heterogeneous catalysts.

The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae. The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.

Background Storage conditions affect the metabolome composition and quality of tobacco leaf and, therefore, its economic value. The present study was designed to reveal tobacco leaves’ dynamic phytochemical and metabolite profile changes under three different storage conditions: natural (NT), mechanical (MC), and air-conditioning (AC). The 210,003 grade (Hubei Central Tobacco) was selected as the experimental material, and the changes in iodine value absorbance (IV), pH, polyphenols, plastid pigments, conventional chemical compositions, and metabolite profile were analyzed at different times (T0, starting day; T1, three months; T2, five months; and T3, nine months) during storage. Results The IV significantly increased with the storage duration, while the pH, polyphenols, and stromal pigments had the opposite trends. Lutein, β-carotene, and chlorogenic acid were significantly less degraded under MC and AC than NT. Neoxanthin and chlorophyll b were completely degraded at T3. The nicotine, total sugar, reducing sugar, and chlorine content significantly varied along with the storage duration, reaching their maximum values at T2 under MC and AC. The sugar/base ratio at T3 under MC and AC was 8.53 and 8.44, respectively, higher than in NT (5.85). LC-MS-based untargeted metabolomics analysis identified 124‒224, 138‒180, and 110‒153 significant differential accumulated metabolites (DAMs) under NT, MC, and AC, respectively. Biosynthesis of secondary metabolites was significantly induced under the three storage conditions between T0 and T3. Glutathione metabolism and oxidative phosphorylation were induced under NT. Biosynthesis of terpenoids and steroids was highly induced under AC. Conclusions Our findings may facilitate the optimization of the storage conditions for better preservation of tobacco leaves. Clinical trial number Not applicable.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP‐43 aggregates. Recent evidence has been indicated that phosphorylated TDP‐43 (pTDP‐43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP‐43 detectable in routine biopsied muscles? (ii) Can detection of pTDP‐43 aggregation discriminate between ALS and non‐ALS patients? (iii) Can pTDP‐43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non‐ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP‐43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP‐43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non‐ALS controls (16/54; p < 0.001). The pTDP‐43 aggregates were mainly close to the sarcolemma. Using a semi‐quantified pTDP‐43 aggregates score, we applied a cut‐off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof‐of‐concept for the detection of pTDP‐43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS. To explore whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS, we conducted a diagnostic study in 18 ALS patients and 54 randomly matched controls from ALS and muscular disease cohorts. Our results indicated that pTDP‐43 was more prone to accumulation in ALS patients, enabling differentiation between ALS and non‐ALS patients with high sensitivity and specificity. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions.