Pd(II)/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Synthesis of Cyclic Quaternary Centers and Mechanistic Investigations.

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

Catalytic (4+2) Annulation via Regio- and Enantioselective Interception of in-situ Generated Alkylgold Intermediate.

A regio- and stereoselective stepwise (4+2) annulation of N-propargylamides and α,ß-unsaturated imines/ketones has been accomplished with synergetic catalysis by a combination of a gold-complex and a chiral quinine-derived squaramide (QN-SQA), leading to highly functionalized chiral tetrahydropyridines/dihydropyrans in good to high yields with generally excellent enantioselectivity. Mechanistic studies and DFT calculations indicate that the in situ formed alkylgold species is the key intermediate in this transformation, and the amide group served as a traceless directing group in this highly selective transformation. This method complements the enantioselective (4+2) annulation of allene reagents, providing the formal internal C-C π-bond cycloaddition products, which is challenging and remains elusive.

Desulfurdioxidative N-N Coupling of N-Arylhydroxylamines and N-Sulfinylanilines: Reaction Development and Mechanism.

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good reaction yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO2.

Arene Reduction by Rh/Pd or Rh/Pt under 1 atm Hydrogen Gas and Room Temperature.

Current methods for arene hydrogenation generally need either harsh reaction conditions or complex catalyst preparation. Here we describe a mild and convenient protocol that only utilizes commercially available catalysts. Using [Rh(nbd)Cl]2 and Pd/C together as catalysts, arenes bearing various functional groups can be hydrogenated under 1 atm of H2 at room temperature. This arene hydrogenation can also be achieved using catalysts of [Rh(cod)Cl]2 and PtO2, thus avoiding glovebox manipulations and simplifying the reaction procedure.

Selective Hydrofunctionalization of Alkenyl Fluorides Enabled by Nickel-Catalyzed Hydrogen Atoms and Group Transfer: Reaction Development and Mechanistic Study.

Due to the unique effect of fluorine atoms, the efficient construction of high-value alkyl fluorides has attracted significant interest in modern drug development. However, enantioselective catalytic strategies for the efficient assembly of highly functionalized chiral C(sp3)-F scaffolds from simple starting materials have been underutilized. Herein, we demonstrate a nickel-catalyzed radical transfer strategy for the efficient, modular, asymmetric hydrogenation and hydroalkylation of alkenyl fluorides with primary, secondary, and tertiary alkyl halides under mild conditions. The transformation provides facile access to various structurally complex secondary and tertiary α-fluoro amide products from readily available starting materials with excellent substrate compatibility and distinct selectivity. Furthermore, the utility of this method is demonstrated by late-stage modifications and product derivatizations. Detailed mechanistic studies and DFT calculations have been conducted, showing that the rate-determining step for asymmetric hydrogenation reaction is NiH-HAT toward alkenyl fluorides and the stereo-determining step is alcohol coordination to Ni-enolates followed by a barrierless protonation. The mechanism for the asymmetric hydroalkylation reaction is also delivered in this investigation.

The Influences of Adverse Childhood Experiences and Social Support on Male Teenagers' Gaming Motivation: A Moderated Network Analysis.

INTRODUCTION: Strong gaming motivations can lead to gaming-related health problems, but how gaming motivations are formed is unclear. Therefore, we examined the impact of early life experiences on gaming motivations. METHODS: Questionnaire data on the gaming motivations, adverse childhood experiences, and social support of 2,171 teenaged online game players were modeled using moderated network analysis. RESULTS: All adverse childhood experience components positively correlated with achievement and escapism motivations (weight range: 0.08-0.40). Social support from friends (weight = -0.04) negatively moderated the relationship between achievement motivation and other adverse childhood experiences and positively moderated (weight = 0.01) the relationship between escapism motivation and familial dysfunction. DISCUSSION: The findings indicate that adverse childhood experiences foster negative gaming motivations. Additionally, social support moderates the relationship between adverse childhood experiences and gaming motivations. These findings offer valuable insights that nursing practitioners can apply to gaming-related health problem interventions and prevention in teenagers.

Dynamically or Kinetically Controlled? Computational Study of the Mechanisms of Electrophilic Aminoalkenylation of Heteroaromatics with Keteniminium Ions.

Quantum chemical calculations and molecular dynamics simulations were applied to study the electrophilic aminoalkenylation of heteroaromatics with keniminium ions. Post-transition state bifurcation (PTSB) was found in the electrophilic addition step for the aminoalkenylation of pyrroles and indoles, and the selectivity for these reactions was dynamically controlled. However, the aminoalkenylation of furan was kinetically controlled because no apparent PTSB was found in the electrophilic addition step. The substituents on the keteniminium ions can also affect the dynamic results for the aminoalkenylations to pyrroles: the C2-aminoalkenylated product is much more favored over the C3-aminoalkenylated product for keteniminium ions with electron-donating substituents, while the product ratio (C2 product/C3 product) decreased when stronger electron-withdrawing substituents were applied.

Rh(I)-Catalyzed [4+3]/[4+1] Cycloaddition of Diene-Vinylcyclopropanes and Carbon Monoxide to Access Angular 5/7/5 Tricycles.

Report here is a Rh-catalyzed [4+3]/[4+1] cycloaddition of diene-vinylcyclopropanes (diene-VCPs) and carbon monoxide to access compounds with angular 5/7/5 tricyclic skeleton found in natural products. The reaction has broad scope and further transformation of the [4+3]/[4+1] cycloadduct was also investigated. How this [4+3]/[4+1] reaction occurs and why its competing [4+3] reaction is disfavored have been investigated computationally.

Profiles of fear of missing out and their social media use among young adults: A six-month longitudinal study.

This longitudinal study used a person-centered approach to differentiate fear of missing out (FoMO) among subgroups of individuals using latent profile analysis (LPA). The subgroups were identified according to trait-FoMO (a specific predisposition) and state-FoMO (a specific cognition in the online context) items. Data were collected from 1125 participants (70.04 % female, age range 17-26 years, Mage = 20.52 years). The LPA showed five distinct profiles: highest FoMO, high trait-FoMO high state-FoMO, high trait-FoMO low state-FoMO, low trait-FoMO high state-FoMO, and low trait-FoMO low state-FoMO. We further explored how these profiles relate to social media use. The results revealed significant differences between profiles in terms of social media engagement, social media self-control failure, and problematic social media use and could be used to predict social media use behaviors of 437 participants (77.35 % female, age range 18-27 years, Mage = 20.60 years) six months later. Thus, the combination of high trait-FoMO and high state-FoMO may mean more frequent social media engagement and could be an important risk factor for social media self-control failure and problematic social media use. Additionally, state-FoMO should be considered in prevention and intervention strategies aimed at addressing young adults' problematic social media use.

Rhodium-Catalyzed [7 + 1] Cycloaddition of Exocyclic 1,3-Dienylcyclopropanes and Carbon Monoxide.

A rhodium-catalyzed [7 + 1] reaction of exocyclic 1,3-dienylcyclopropanes and carbon monoxide has been developed to synthesize eight-membered carbocycle-embedded bicyclic and tricyclic molecules. In addition, ab initio calculations were conducted to reveal the reaction mechanism.

Prokineticin-2 Participates in Chronic Constriction Injury-Triggered Neuropathic Pain and Anxiety via Regulated by NF-κB in Nucleus Accumbens Shell in Rats.

Neuropathic pain (NP) is an intractable pain that results from primary nervous system injury and dysfunction. Herein, we demonstrated in animal models that peripheral nerve injury induced enhanced pain perception and anxiety-like behaviors. According to previous reports, nucleus accumbens (NAc) shell is required for complete expression of neuropathic pain behaviors and mood alternations, we found the elevated mRNA and protein level of Prokineticin-2 (Prok2) in the NAc shell after Chronic Constriction Injury (CCI). Prok2 knockdown in the NAc shell reversed NP and anxiety-like behaviors in rats, indicating that Prok2 might play a fundamental role in NP and anxiety co-morbidity. CCI significantly enhanced Prok2 co-expression with NF-κB P-p65 in comparison with control animals. In addition to reversing the established nociceptive hypersensitivities and anxiety simultaneously, NAc microinjection of NF-κB siRNA or specific inhibitor PDTC reversed Prok2 upregulation. Besides, Prok2 was significantly decreased in vitro when co-transfected with si-NF-κB. Dual-Luciferase assay showed NF-κB directly activated Prok2 gene transcriptional activity. Overall, these findings provide new insights into the neurobiological mechanisms behind NP and comorbid anxiety. The NF-κB/Prok2 pathway could be a potential therapeutic target for NP and anxiety disorders.

Roles of Twist1 in lipid and glucose metabolism.

The abnormal lipid and glucose metabolisms are linked to the metabolic disorders, tumorigenesis, and fibrotic diseases, which attracts the increasing attention to find out the key molecules involved in the lipid and glucose metabolism as the possible therapeutic targets on these diseases. A transcriptional factor Twist1 has been associated with not only the embryonic development, cancer, and fibrotic diseases, but also the regulation of lipid and glucose metabolism. In this review, we will discuss the roles and mechanisms of Twist1 in the obesity-associated white adipose tissue inflammation and insulin resistance, brown adipose tissue metabolism, fatty acid oxidation, and glucose metabolism in skeletal muscle to provide a rational perspective to consider Twist1 as a potential treatment target in clinic. Video Abstract.

Catalytic 4-exo-dig carbocyclization for the construction of furan-fused cyclobutanones and synthetic applications.

Cyclobutanone is a strained motif with broad applications, while direct assembly of the aromatic ring fused cyclobutanones beyond benzocyclobutenone (BCB) skeletons remains challenging. Herein, we report a Rh-catalyzed formal [3+2] annulation of diazo group tethered alkynes involving a 4-exo-dig carbocyclization process, providing a straightforward access to furan-fused cyclobutanones. DFT calculations disclose that, by comparison to the competitive 5-endo-dig process, 4-exo-dig carbocyclization is mainly due to lower angle strain of the key sp-hybridized vinyl cationic transition state in the cyclization step. Using less reactive catalysts Rh2(carboxylate)4 is critical for high selectivity, which is explained as catalyst-substrate hydrogen bonding interaction. This method is proved successful to direct access previously inaccessible and unknown furan-fused cyclobutanone scaffolds, which can participate in a variety of post-functionalization reactions as versatile synthetic blocks. In addition, preliminary antitumor activity study of these products indicates that some molecules exhibite significant anticancer potency against different human cancer cell lines.

Experimental-based statistical models for the tensile characterization of synthetic fiber ropes: a machine learning approach.

This study investigated the tensile behavior of some prevalent synthetic fiber ropes made of polyester, polypropylene, and nylon polymeric fibers. The aim was to generate well-documented experimental statistics and develop simplified stress-strain constitutive laws that can describe the ropes' tensile response. The methodology involved analyzing the thermal history of the fibers using the DSC technique, tensile testing of fibers and yarn components of the rope, and conducting 196 rope tensile tests with optimum testing conditions. Based on the test results, an experimental database of the ropes' tensile characteristics was established, containing different parameters of material properties, rope construction, fiber processing, fiber tensile properties, and rope tensile responses. Subsequently, ANN models were developed and optimized using MATLAB based on the generated dataset's inputs and outputs to predict the studied ropes' tri-linear stress-strain profiles. The results showed that the ANN models accurately predicted the stress-strain properties of ropes represented by the tri-linear approximation with an error of about 5% for the failure strength and strain. The study provides insight into the process-structure-property relationship of synthetic fiber ropes and contributes to minimizing the cost and effort in designing and predicting their tensile properties while contributing to the practical industry.

Rh-Catalyzed [4 + 1] Reaction of Cyclopropyl-Capped Dienes (but not Common Dienes) and Carbon Monoxide: Reaction Development and Mechanistic Study.

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) is the most straightforward and easily envisioned cyclization for the synthesis of five-membered carbocycles, which are ubiquitously found in natural products and functional molecules. Unfortunately, no test of this reaction was reported, and consequently, chemists do not know whether such kind of reaction works or not. Herein, we report that the [4 + 1] reaction of common dienes and CO cannot work, at least under the catalysis of [Rh(cod)Cl]2. However, using cyclopropyl-capped dienes (also named allylidenecyclopropanes) as substrates, the corresponding [4 + 1] reaction with CO proceeds smoothly in the presence of [Rh(cod)Cl]2. This [4 + 1] reaction, with a broad scope, provides efficient access to five-membered carbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadducts can be further transformed into other molecules by using the unique chemistry of cyclopropyl groups present in these molecules. The mechanism of this [4 + 1] reaction has been investigated by quantum chemical calculations, uncovering that cyclopropyl-capped dienes are strained dienes and the oxidative cyclization step in the [4 + 1] catalytic cycle can release this (angular) strain both kinetically and thermodynamically. The strain release in this step then propagates to all followed CO coordination/CO insertion/reductive elimination steps in the [4 + 1] catalytic cycle, helping the realization of this cycloaddition reaction. In contrast, common dienes (including cyclobutyl-capped dienes) do not have such advantages and their [4 + 1] reaction suffers from energy penalty in all steps involved in the [4 + 1] catalytic cycle. The reactivity of ene-allenes for the [4 + 1] reaction with CO is also discussed.

Cell Profiling of Acute Kidney Injury to Chronic Kidney Disease Reveals Novel Oxidative Stress Characteristics in the Failed Repair of Proximal Tubule Cells.

Chronic kidney disease (CKD) is a major public health issue around the world. A significant number of CKD patients originates from acute kidney injury (AKI) patients, namely "AKI-CKD". CKD is significantly related to the consequences of AKI. Damaged renal proximal tubular (PT) cell repair has been widely confirmed to indicate the renal prognosis of AKI. Oxidative stress is a key damage-associated factor and plays a significant role throughout the development of AKI and CKD. However, the relationships between AKI-CKD progression and oxidative stress are not totally clear and the underlying mechanisms in "AKI-CKD" remain indistinct. In this research, we constructed unilateral ischemia-reperfusion injury (UIRI)-model mice and performed single-nucleus RNA sequencing (snRNA-seq) of the kidney samples from UIRI and sham mice. We obtained our snRNA-seq data and validated the findings based on the joint analysis of public databases, as well as a series of fundamental experiments. Proximal tubular cells associated with failed repair express more complete senescence and oxidative stress characteristics compared to other subgroups. Furthermore, oxidative stress-related transcription factors, including Stat3 and Dnmt3a, are significantly more active under the circumstance of failed repair. What is more, we identified abnormally active intercellular communication between PT cells associated with failed repair and macrophages through the APP-CD74 pathway. More notably, we observed that the significantly increased expression of CD74 in hypoxia-treated TECs (tubular epithelial cells) was dependent on adjacently infiltrated macrophages, which was essential for the further deterioration of failed repair in PT cells. This research provides a novel understanding of the process of AKI to CKD progression, and the oxidative stress-related characteristics that we identified might represent a potentially novel therapeutic strategy against AKI.

First report of 'Candidatus Phytoplasma asteris' associated with witches'-broom disease of Pinus yunnanensis in China.

Pinus yunnanensis is an evergreen tree belonging to Pinaceae. The species is distributed in the east of Tibet, southwest of Sichuan, southwest of Yunnan, southwest of Guizhou and northwest of Guangxi. It is an indigenous and pioneer tree species for barren mountain afforestation in southwest China. P. yunnanensis has important value to both the building and medicine industries (Liu et al. 2022). In May 2022, P. yunnanensis showing witches'-broom symptom were found in Panzhihua City, Sichuan Province, China. The symptomatic plants had yellow or red needle, and exhibited plexus bud and needle wither. The lateral buds of infected pines developed into twigs. Some lateral buds grew in clusters and a few sprouted needles (Fig.1). The disease was named the P. yunnanensis witches'-broom disease (PYWB) and was found in some areas of Miyi, Renhe, and Dongqu. More than 9% of the pines showed these symptoms in the three areas surveyed, and the disease was spreading. A total of 39 samples were collected from three areas, including 25 symptomatic plants and 14 asymptomatic plants, respectively. The lateral stem tissues of 18 samples were observed under a scanning electron microscope (Hitachi S-3000N). Spherical bodies were found in the phloem sieve cells of symptomatic pines (Fig.1). Total DNA was extracted from 18 plant samples using the CTAB method (Porebski et al. 1997) and subjected to nested-PCR testing. Double-distilled water and DNA extracted from asymptomatic plants were used as negative controls, and DNA extracted from Dodonaea viscosa affected by the D. viscosa witches'-broom disease was used as positive control. Nested PCR was employed to amplify the pathogen's 16S rRNA gene (Lee et al. 1993; Schneider et al. 1993) and 1.2 kb segment were produced (GenBank accessions OP646619; OP646620; OP646621). PCR specific to the ribosomal protein (rp) gene yielded segment of approximately 1.2 kb (Lee et al. 2003)(GenBank accessions OP649589; OP649590; OP649591). The fragment size from 15 samples was consistent with the positive control, confirming the association of phytoplasma with the disease. A BLAST analysis of the 16S rRNA sequences of P. yunnanensis witches'-broom phytoplasma showed that it shared 99.12% ~99.76% identity with that of Trema laevigata witches'-broom phytoplasma (GenBank accession MG755412). The rp sequence shared 99.84%~99.92% identity with that of Cinnamomum camphora witches'-broom phytoplasma (GenBank accession OP649594). An analysis with iPhyClassifier (Zhao et. 2013) showed that the virtual RFLP pattern derived from OP646621 16S rDNA fragment of PYWB phytoplasma is identical (similarity coefficient 1.00) to the reference pattern of 16Sr group I, subgroup B (OY-M, GenBank accession AP006628). The phytoplasma is identified as a 'Candidatus Phytoplasma asteris'-related strain belonging to sub-group 16SrI-B. Interestingly, compared to AP006628, the virtual RFLP pattern derived from OP646619 and OP646620 fragments exhibit differences in three and one cleavage site, with a similarity coefficient of 0.92 and 0.97, respectively (Fig.2). These strains may represent a new subgroup within the 16Sr group I. The phylogenetic tree was reconstructed based on 16S rRNA and rp gene sequences using MEGA versio6.0 (Tamura et al. 2013). The analysis was conducted using the neighbor-joining (NJ) method with 1,000 replicates of bootstrap analysis. The results indicated that the PYWB phytoplasmas grouped into clades including phytoplasmas belonging to 16SrI-B and rpI-B, respectively (Fig.3). In addition, 2-year-old P. yunnanensis were used for grafting assays in nursery, and the twigs from infected pine under natural conditions were used as a scion, and the phytoplasma were detected using nested PCR after grafting for 40 d (Fig.4). In 2008-2014, P. sylvestris and P. mugo in Lituania had excessive branching symptoms that were attributed to 'Ca. Phtyoplasma Pini' (16SrXXI-A) or asteris' (16SrI-A) strains (Valiunas et al. 2015). In 2015, P. pungens with abnormal shoot branching in Maryland were found to be infected by 'Ca. Phytoplasma pini' strain (16SrXXI-B) (Costanzo et al. 2016). To the best of our knowledge, P. yunnanensis is a new host of 'Ca. Phytoplasma asteris'-related strain (16SrI-B) in China. The newly emerged disease is a threat to pines.

A meta-analysis and bioinformatics analysis of P4HB expression levels in the prognosis of cancer patients.

BACKGROUND: P4HB (prolyl 4-hydroxylase, beta polypeptide) is a human chromosomal gene that encodes an endoplasmic reticulum (ER) molecular chaperone protein with oxidoreductase, chaperone and isomerase activities. Recent studies indicated that P4HB may have clinical significance, with elevated P4HB expression reported in cancer patients, but its impact on tumor prognosis is not yet clear. To our knowledge, this is the first meta-analysis to show an association between P4HB expression and the prognosis of various cancers. METHODS: We conducted a systematic literature search in the PubMed, PubMed Central, Web of Science, Embase, CNKI, Wanfang and Weipu databases, followed by a quantitative meta-analysis using Stata SE14.0 and R statistics software 4.2.1. The hazard ratio (HR) and relative risk (RR) were analyzed to evaluate the relationships of P4HB expression levels with overall survival (OS), disease-free survival (DFS), and clinicopathological parameters of cancer patients. Subsequently, P4HB expression in various cancer types was validated using the Gene Expression Profiling Interactive Analysis (GEPIA) online database. RESULTS: Ten articles containing the data of 4121 cancer patients were included in the analysis, and a significant correlation of high P4HB expression with apparently shorter OS was found (HR, 1.90; 95% CI, 1.50-2.40; P < 0.01), while there was no significant correlation with gender (RR, 1.06; 95% CI, 0.91-1.22; P = 0.084), or age. Additionally, GEPIA online analysis revealed significant upregulation of P4HB in 13 types of cancer. Among them, P4HB overexpression was associated with shorter OS in 9 and worse DFS in 11 cancer types. CONCLUSIONS: Upregulation of P4HB is correlated with worse prognosis in various cancers, which could provide new ideas for the development of P4HB-related diagnostic biomarkers and new therapeutic targets.

Kinetic, Thermodynamic, and Dynamic Control in Normal vs. Cross [2 + 2] Cycloadditions of Ene-Keteniminium Ions: Computational Understanding, Prediction, and Experimental Verification.

Almost all reported intramolecular [2 + 2] reactions of ene-keteniminium ions gave normal [2 + 2] products with a fused bicycle framework, but not cross [2 + 2] products with a bicyclo[3.1.1]heptane skeleton, a highly pursued bioisostere in pharmaceutical chemistry. How to rationalize this and design new cross [2 + 2] reactions? Theoretical studies using density functional theory, high-level ab initio single-point energy calculations, and molecular dynamics showed that this [2 + 2] reaction has all three patterns of regiochemical control: the reaction is controlled either kinetically, thermodynamically, or dynamically. A carbocation model of forming endo and exo carbocations has been proposed to rationalize the reaction outcomes, revealing that the tethers (between alkenes and keteniminium ions), substituents (on the alkenes), and alkene configurations in ene-keteniminium ions play critical roles. These understandings were further used to predict that introducing a substituent in the terminal position of alkene with a trans configuration in ene-keteniminium ions can realize the cross [2 + 2] reaction, which is dynamically controlled for alkyl substituents or kinetically controlled for aryl substituents. These and more other predictions were realized experimentally, and many cross [2 + 2] products with a bicyclo[3.1.1]heptane skeleton can be achieved. Both molecular dynamics and new experiments have also been applied to correct a key but misassigned [2 + 2] product reported in the literature, further supporting the insightful mechanisms reported here.

Synthesis of Polycyclic n/5/8 and n/5/5/5 Skeletons Using Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Exocyclic-ene-vinylcyclopropanes and Carbon Monoxide.

A rhodium-catalyzed [5 + 2 + 1] reaction of exocyclic-ene-vinylcyclopropanes (exo-ene-VCPs) and CO has been realized to access challenging tricyclic n/5/8 skeletons (n = 5, 6, 7), some of which are found in natural products. This reaction can be used to build tetracyclic n/5/5/5 skeletons (n = 5, 6), which are also found in natural products. In addition, 0.2 atm CO can be replaced by (CH2O)n as the CO surrogate to achieve the [5 + 2 + 1] reaction with similar efficiency.