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We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.

Diffuse large B-cell lymphoma (DLBCL) is a group of heterogeneous tumors with different molecular traits and clinical features. MYD88 is an oncogene that activates the nuclear factor κB pathway in DLBCL. MYD88 L265P mutation frequently occurs in DLBCL with poor prognosis, while the clinical significance of non-L265P mutations needs to be clarified. Next-generation sequencing was performed on a cohort of 356 patients with DLBCL to investigate the impact of MYD88 mutation. Ten MYD88 mutated variants were detected in 32% (114/356) of the cases. V217F, S219C, S222R, M232T, S243N, and T294P were identified as pathogenic variants. MYD88 non-L265P mutations occurred less than L265P mutation in DLBCL of the central nervous system and breast tissue. The coexistence of MYD88 non-L265P mutations with PIM1 mutation was also less than that of L265P mutation. The progression-free survival in patients with DLBCL with MYD88 non-L265P mutation was statistically better than in patients with MYD88 L265P mutation. The interpretation of variants of MYD88 mutation offers a precise guide for the management of DLBCL.

This article explores how the Chinese government aims to maintain social stability by encouraging citizens to become volunteers. We propose that a new type of governance, namely, “state-enlisted voluntarism,” is being deployed in which public security volunteers are mobilized and monitored by the state. Analysis based on ten-year nationwide empirical data gathered from local areas in China suggests that the government intentionally enlists citizens into its hierarchical system to strengthen its administrative capacity and maintain a stable society without the risk of domestic threats. We find that direct enlistment approaches empower citizens as state proxies, and that indirect enlistment approaches ensure that various social stakeholders are comprehensively controlled. In general, the Chinese government has four reasons to institutionalize the state enlistment of voluntarism: to increase human resources at the grassroots; transform social organizations into subordinates; frame policy innovations as political credits; and to avoid blame. Our findings also suggest that China's party-state system mobilizes citizens into implementation-oriented activities rather than engages them in policymaking to maintain social stability at the grassroots.

Crim1 has been implicated in cataracts in mice and is of great importance in the development of the eye in both humans and mice. Therefore, we aimed to clarify how Crim1 mutations affect lens development and the molecular mechanism of cataracts in mice through comprehensive bioinformatics analysis. The microarray chip was downloaded from the GEO database to obtain the gene expression profile data set. Differentially expressed genes (DEGs) were screened using the limma package. GO and KEGG analyses of DEGs were performed using the DAVID database. Then, we established the protein–protein interaction (PPI) network in Cytoscape. Next, we used MCODE to analyze the data. We obtained 750 DEGs in total, including 407 upregulated DEGs and 343 downregulated DEGs. GO analysis showed that the DEGs were mainly related to biological processes, such as apoptosis, cell translation and the immune system. KEGG analysis showed that the enriched functions and pathways were related to the processing and presentation of ribosomes, lysosomes, and antigens. We identified 18 HUB genes, among which four core genes, C1qa, C1qb, C1qc, and Cd74, were closely related to congenital cataracts induced by Crim1 mutation. This study reveals the molecular pathogenesis of congenital cataracts induced by Crim1, and this information is expected to facilitate clinical genetic testing, molecular diagnosis, prognosis, and individualized chemotherapy for congenital cataracts (CC).

We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery.The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary

Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation.Plasma levels of YY1, interleukin (IL) 6, and IL-1β in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1β inflammatory pathway were measured in related brain regions.Plasma levels of YY1 and IL-1β were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1β in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1β inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine.The current study suggests that the YY1-NF-κB-IL-1β inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Asymmetric ketene cycloaddition is a powerful tool for chiral heterocycle synthesis, stimulating the development of innovative catalytic strategies to achieve a high level of efficiency and stereocontrol. Herein, we disclose an asymmetric cascade reaction between enynamides and α-diazoketones inspired by natural photosynthesis. The biomimic combination of visible-light photoactivation and relay gold and N-oxide catalysis allowed the facile generation and controlled assembly of two reactive intermediates, ketene and aza-o-quinone methide. This produced chiral bicyclic lactams bearing chiral all-carbon quaternary stereocenters with high efficiency and selectivity. Density functional theory calculations revealed a stepwise [4+2] cycloaddition mechanism, with the stereochemistry controlled by the amide group of the catalyst. Notably, this study presents the first example of chiral N-oxides as catalysts for asymmetric ketene cycloaddition, and demonstrates that a biomimetic cascade strategy is a promising approach to access important chiral heterocyclic scaffolds.

Introduction Demodex and bacteria are both components of the ocular surface micro-ecology, constituting a complex interaction. This study aims to explore how ocular surface Demodex infestation (DI) affects ocular surface microbial communities and diversity. Methods We recruited 255 subjects, and examined the correlation between ocular surface mite infestation and clinical indicators such as age, blood glucose level, dry eye symptoms, and blood pressure. 16S rRNA sequencing was performed on the conjunctival swab samples of 14 patients with ocular DI (P group) and 17 healthy people (N group). For further analysis, the subjects were divided into four subgroups, i.e. N-NMGD (n = 11), N-MGD (n = 6), P-NMGD (n = 6), and P-MGD (n = 8), according to meibomian gland dysfunction (MGD) or no MGD (NMGD). Results There was no difference in the α-diversity of ocular surface microbial communities between the DI and healthy control groups. In linear discriminant analysis effect size (LEfSe), there were more Acinetobacter, Novosphingobium, and Anoxybacillus in the DI group and fewer Novosphingobium, Lactobacillus, and Candidatus Microthrix in the healthy control group. P-NMGD had more Thermaceae and fewer Pseudomonas than P-MGD. There were more Bacteroidetes in N-NMGD than in N-MGD. The α-diversity of P-NMGD was lower than that of N-NMGD (Shannon index, P = 0.027). At the same time, the α-diversity of N-MGD was lower than that of N-NMGD (Shannon, Simpson, and dominance index, P = 0.048). There was no significant difference in β-diversity or in the primary flora at the phylum and genus levels between groups and subgroups. Conclusion DI had no significant effect on the diversity of ocular surface microbial communities. DI primarily changed the dominant flora and relative abundance of ocular surface microbial communities. MGD may play an important role in this process.

Predicting the direction of the stock market has always been a huge challenge. Also, the way of forecasting the stock market reduces the risk in the financial market, thus ensuring that brokers can make normal returns. Despite the complexities of the stock market, the challenge has been increasingly addressed by experts in a variety of disciplines, including economics, statistics, and computer science. The introduction of machine learning, in-depth understanding of the prospects of the financial market, thus doing many experiments to predict the future so that the stock price trend has different degrees of success. In this paper, we propose a method to predict stocks from different industries and markets, as well as trend prediction using traditional machine learning algorithms such as linear regression, polynomial regression and learning techniques in time series prediction using two forms of special types of recursive neural networks: long and short time memory (LSTM) and spoken short-term memory.

A growing number of clinical and preclinical studies suggest that alterations in peripheral and brain immunal system and followed inflammation are associated with the pathophysiology of depression, also leading to the changes in local glucose metabolism in the brain. Here, we identified Yin-yang 1 (YY1), a transcription factor that has been reported to be closely associated with central and peripheral inflammation. The levels of YY1 and IL-1β were significantly increased in blood samples from depressed individuals, and significantly decreased after treatment with Vortioxetine. Meanwhile, it was found that the level of YY1 in plasma was negatively correlated with visual learning reasoning and problem solving in MDD patients, and positively correlated with the level of IL-1β in plasma. CUMS animals showed depressive-like behavior. Compared with the control group, MicroPET analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum and mPFC was reversed after treatment. After treatment, these changes were reversed. In conclusion, Our study suggested that YY1-NF-κB - IL-1β inflammatory pathway may play an essential part on both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in the emotion regulation and cognition related brain regions. These findings provide new evidence for the inflammatory mechanisms of depression.

Gastrointestinal symptoms are not uncommon in patients infected withA 41-year-old female with acquired immune deficiency syndrome (AIDS) was admitted to our hospital for long-term fever, followed by abdominal pain and diarrhea. The colonoscopy performed in our hospital revealed ulcerative lesions in the colon and terminal ileum. Periodic acid-Schiff (PAS) staining of intestinal ulcer revealed that the small dots distributed inside and outside of the macrophages were yeast microorganisms. Further culture of bone marrow sample was confirmedIn HIV-infected and other immunocompromised patients with gastrointestinal symptoms and/or associated abdominal imaging abnormalities, intestinalAIDS: acquired immune deficiency syndrome; ART: antiretroviral therapy; ESR: erythrocyte sedimentation rate; PPD:purified protein derivative; HE: Hematoxylin and eosin; PAS: Periodic acid-Schiff; CMV: cytomegalovirus; GMS:Gomori's methenamine silver nitrate.

This article examines how the Chinese government increases the effectiveness of policy implementation by resorting to citizen participation. Based on an in-depth case study of the waste classificat...

First-row transition-metal catalysis has been attracting great attention in recent years, partly due to its low toxicity and low cost, as well as a wide variety in reactivities. However, the theore...

The first enantioselective alkynylation of benzylic C-H bonds via copper-catalyzed radical relay has been established herein, which provides an easy access to structurally diverse benzylic alkynes in good yields with excellent enantioselectivities. A key step for the asymmetric copper-catalyzed radical relay process is the enantioselective capture of a benzylic radical with chiral (Box)CuII-alkynyl species. In addition, the reaction displays good functional group tolerance, broad substrate scope, and mild conditions. The enantioenriched alkynylation products can be readily transformed into highly valuable synthons, such as chiral terminal alkynes, allenes, alkenes, and carboxylic acids. More importantly, our methodology can be applied to the synthesis of bioactive molecule AMG 837.

Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.

To describe and analyze clinical characteristics of multifocal choroiditis with linear streaks (LSs).Eight cases of multifocal choroiditis with LSs were retrospectively studied. Multimodal imaging was performed. Demographic data and spherical equivalent were collected. Axial length was measured.All cases are young myopic women with a mean age of 17.13 ± 3.64 years (range, 13-23 years), presenting with vision loss and distortion. Nine eyes with LSs were high myopia of -8.97 ± 2.69 D (range, -6.00 to 12.5 D; growing by 1.88 ± 0.61 D annually since wearing glasses), with mean axial length of 26.36 ± 1.71 mm. Vitreous cells were noted in seven eyes. LSs were located in the equator (eight eyes), around the optic disk (three eyes), and at the edge of the posterior pole (one eye). Angio-optical coherence tomography showed choroidal neovascularization in eight eyes, especially 2 to 3 choroidal neovascularizations in three eyes. The location of choroidal neovascularization were in subfovea (three eyes), parafovea (six eyes), and perifovea (two eyes). Swept source optical coherence tomography showed punched-out disruption of retinal pigment epithelium‒Bruch's membrane‒choriocapillaris complex at the LSs' sites. LSs showed fluorescence staining on late FA but hypofluorescence throughout all phases on ICGA.Multifocal choroiditis with LSs mostly occurs in young women with high myopia, especially occurring in eyes with rapid progression of myopia. LSs are mainly located in the midperiphery near the equator, being prone to concur with choroidal neovascularization. Based on our findings, we propose a new term called "streaky multifocal choroiditis" as a subtype of multifocal choroiditis.

Multiple sclerosis is a chronic demyelinating disease of uncertain etiology. Traditional treatment methods produce more adverse effects. Epidemiological and clinical treatment findings showed that unknown environmental factors contribute to the etiology of MS and that diet is a commonly assumed factor. Despite the huge interest in diet expressed by people with MS and the potential role diet plays in MS, very little data is available on the role of diet in MS pathogenesis and MS course, in particular, studies on fats and MS. The oil ofHere, we investigated the underlying influences ofCuprizone (0.2% in chow) was used to establish a mouse model of demyelination.Mice exposed to cuprizone for 6 weeks showed schizophrenia-like behavioral changes, the increased exploration of the center in the open field test (OFT), increased entries into the open arms of the elevated plus-maze, as well as demyelination in the corpus callosum. After cuprizone withdrawal, the diet therapy was initiated with supplementation ofDiet supplementation with

Purpose To describe and analyze the clinical prognosis of infants diagnosed of familial exudative vitreoretinopathy (FEVR) with single gene mutation in long-term follow-up. Methods A retrospective case study was conducted on 355 FEVR infants with single positive gene. Result Of the 335 single-gene positive infant FEVR cases (under 3 years old), 20% (n = 67) was diagnosed of strabismus at first visit. Staging of various genotypes was different (P th stage 75 of 108 [69.44%]). The axial length of different genotypes showed no significant difference (P = 0.2891). The 1st to 3rd stage cases were given intravitreal injection and/or retina photocoagulation with the last follow-up vision above 20/67. The 4th to 5th stage cases received the transcorneal vitrectomy with lensectomy or lens sparing vitrectomy (LSV), whose lens maintained transparent after LSV (11/14[78.58%]). After 2 to 10 years of follow-up, 37.96% (41/108) of post-surgery cases showed retinal funnel-like unfold and posterior pole unfold, 69.57% (16/ 23) of which received second surgery for closure of pupil with good prognosis. At the last follow-up, 20% (60/300) were with vision above 20/200. Conclusion LRP5 gene mutation was the most common mutation in FEVR patients. The severity of the clinical phenotype varied with different gene mutations. The main surgical methods for cases at Stage 4–5 were transcorneal vitrectomy with lensectomy or LSV. The earlier FEVR occurred, the worse prognosis would be. Active surgical intervention and lens sparing were necessary for cases at Stage 4–5.

We reported 46 cases of Diffuse Large B-cell lymphoma which abnormally expressed CD5 protein (De Novo CD5-positive DLBCL), which had attracted researcher's attention for a period of time for its poor prognosis. However, there were few studies on its molecular change. In the present article, we summarized the genetic alterations using a lymphopanel detection method by Next Generation Sequencing(NGS). The most frequently mutated genes were MYD88

In order to improve the catalytic activity and recycling performance of semiconductor activators, and improve the activation pathway of persulfate, graphitic carbon nitride (g-C3N4) was prepared by calcining melamine, and a composite activator Ag2O/g-C3N4 based on g-C3N4 supported metal oxide was prepared using a precipitation method. The morphology, structure, and basic properties of the composites were characterized using SEM, XRD, FT-IR and XPS. The activation efficiency of the Ag2O/g-C3N4 composite activator on peroxodisulfate (PDS) was explored. The results showed that Ag2O in the composite activator was highly dispersed on the surface of g-C3N4 and did not change the molecular structure of g-C3N4 significantly. Under different activation systems, the degradation process of MO was best fitted under the pseudo-second-order reaction kinetic model, compared to the separate g-C3N4 or Ag2O activated PDS systems; the activation of the PDS system with Ag2O/g-C3N4 had the best effect on MO degradation; and the composite activator Ag2O/g-C3N4 showed better activation performance. Under the conditions that the mass combined ratio of Ag2O in the activator was 12%, the initial concentration of PDS was 4 mmol/L, the initial concentration of the activator was 1.25 g/L, and the initial pH was 3, the degradation degree of MO reached 99.4% after 40 min reaction. The free radical quenching experiment proved that the active substances that could degrade MO in the system were SO4−· and ·OH, and the effect of SO4−· was greater than that of ·OH. The degradation degree of MO in the reaction system remained above 80% after four cycles of use, and the crystal structure of Ag2O/g-C3N4 did not change significantly before and after the reaction. The above results show that Ag2O/g-C3N4 is an efficient and stable composite activator with good application potential in the treatment of dye wastewater by activating PDS.

Conventional PID control, although has the advantage that the robustness and adaptability, has certain limitations, but for nonlinear systems is difficult to achieve the desired effect. When the environment changes, control parameters cannot be adjusted in time. Aiming at these problems, this paper presents an improved PID control strategy based on genetic algorithm. Taking single-phase LCL as the research object, by analyzing the operation process of single-phase LCL grid-connected inverter and optimizing genetic algorithm, the genetic iteration process is optimized through adaptive adjustment, and the weight of objective function is adjusted, so that the system can respond quickly, better monitoring of grid-connected current improves the robustness of the system. So as to better ensure the stability of grid connection. Finally, the MATLAB model is built for simulation. Simulation endings indicate that the boosted control strategy has great stability and can effectively decrease the grid current harmonic content. The improved algorithm is global and has relatively high error tolerance, which can meet the needs of grid connection.

Neuromorphic hardware implementation of Boltzmann Machine using a network of stochastic neurons can allow non-deterministic polynomial-time (NP) hard combinatorial optimization problems to be efficiently solved. Efficient implementation of such Boltzmann Machine with simulated annealing desires the statistical parameters of the stochastic neurons to be dynamically tunable, however, there has been limited research on stochastic semiconductor devices with controllable statistical distributions. Here, we demonstrate a reconfigurable tin oxide (SnOx)/molybdenum disulfide (MoS2) heterogeneous memristive device that can realize tunable stochastic dynamics in its output sampling characteristics. The device can sample exponential-class sigmoidal distributions analogous to the Fermi-Dirac distribution of physical systems with quantitatively defined tunable “temperature” effect. A BM composed of these tunable stochastic neuron devices, which can enable simulated annealing with designed “cooling” strategies, is conducted to solve the MAX-SAT, a representative in NP-hard combinatorial optimization problems. Quantitative insights into the effect of different “cooling” strategies on improving the BM optimization process efficiency are also provided., Boltzmann Machines offer the potential of more efficient solutions to combinatorial problems compared to von Neumann computing architectures. Here, Yan et al introduce a stochastic memristor with dynamically tunable properties, a vital feature for the efficient implementation of a Boltzmann Machine.

The proposed structures of parvistemoamide have been achieved by macrolactamization, but none of the characterization data of synthetic samples matched with those of the natural sample. The transformation of the highly strained 10-membered lactam ring in parvistemoamide into the pyrrolo[1,2-a]-azepine nucleus in stemoamide is accomplished for the first time by either transannular cyclization or Pilli's transformation. This research may promote the total synthesis of other more complex stemoamide-type or medium-sized-ring-containing Stemona alkaloids.

Described here is a direct catalytic asymmetric functionalization of unactivated alkyl indoles using organocatalysis. In the presence of an effective chiral urea catalyst and a phosphoric acid additive, the intermolecular C-C bond formation between alkyl indoles and trifluoropyruvates proceeded with high efficiency and enantiocontrol. Unlike previous asymmetric C(sp3 -H) functionalizations of α-azaarenes, this process does not require the use of either a strong base or an electron-deficient substrate. The excellent enantiocontrol is particularly noteworthy in view of the severe background reaction as well as the complete inability of other types of catalysts evaluated. Control experiments, kinetic studies, and DFT calculations provided important insights into the mechanism.

Facile synthesis and bio-applications of a series of AIEgens with widely tunable emissions ranging from violet to near-infrared are reported., Luminogens with aggregation-induced emission (AIE) characteristics are nowadays undergoing explosive development in the fields of imaging, process visualization, diagnosis and therapy. However, exploration of an AIE luminogen (AIEgen) system allowing for extremely wide color tunability remains challenging. In this contribution, the facile synthesis of triphenylamine (TPA)–thiophene building block-based AIEgens having tunable maximum emission wavelengths covering violet, blue, green, yellow, orange, red, deep red and NIR regions is reported. The obtained AIEgens can be utilized as extraordinary fluorescent probes for lipid droplet (LD)-specific cell imaging and cell fusion assessment, showing excellent image contrast to the cell background and high photostability, as well as satisfactory visualization outcomes. Interestingly, quantitative evaluation of the phototherapy effect demonstrates that one of these presented AIEgens, namely TTNIR, performs well as a photosensitizer for photodynamic ablation of cancer cells upon white light irradiation. This study thus provides useful insights into rational design of fluorescence systems for widely tuning emission colors with high brightness, and remarkably extends the applications of AIEgens.

High-performance pressure sensors have attracted considerable attention recently due to their promising applications in touch displays, wearable electronics, human–machine interfaces, and real-time physiological signal perception. However, the “functionality” of a sensor is generally incompatible with “simple” fabrication strategies. Therefore, strategies that are less equipment-intensive and less expensive are required for enhancing the sensor performance. Here, we propose a flexible piezoresistive pressure sensor based on MXene–textile prepared by a facile dip-coating process. Benefiting from the excellent electrical properties of MXene and the abundant wavy surface of cotton textile, this pressure sensor exhibits high sensitivity (12.095 kPa−1 for the range 29–40 kPa and 3.844 kPa−1 for the range less than 29 kPa) with a rapid response time of 26 ms, and excellent cycling stability (5600 cycles). The real-time monitoring of human physiological signals such as wrist pulse, voice detection, and finger movements can be achieved by using this MXene–textile sensor. In addition, sensory arrays were successfully applied in the pressure distribution mapping of a key, demonstrating that the pressure sensor can be used as part of wearable devices and human–machine interfaces to sense pressure.