Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.

Probiotic Compounds Enhanced Recovery after Surgery for Patients with Distal Gastric Cancer: A Prospective, Controlled Clinical Trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.

Dietary Factors and the Risk of Colorectal Cancer: A Mendelian Randomization Study.

OBJECTIVE: To examine the causal association between 15 dietary factors and the incidence of colorectal cancer through the application of Mendelian randomization methodology. METHODS: The data associated with 15 dietary factors were derived from the IEU OPEN GWAS database, and the colorectal cancer data were sourced from the FinnGen database. The Inverse Variance Weighting method was the principal research method. Sensitivity analyses were implemented to affirm the robustness of the findings. Additionally, we conducted multivariable Mendelian randomization analyses to adjust for the intake of ω-3 and ω-6 polyunsaturated fatty acids. RESULTS: In our research, we observed suggestive causal relationships between genetically predicted water intake and the reduced risk of colorectal cancer (OR = 0.54; 95% CI= 0.31 ∼ 0.93; p = 0.028); genetically predicted ω-3 PUFA intake (OR = 1.17; 95% CI= 1.05 ∼ 1.30; p = 0.005) were suggestively associated with the increased risk of colorectal cancer. In the multivariable Mendelian randomization analysis, the effect of ω-3 PUFA intake remains significant after adjusting for the influence of ω-6 PUFA intake. Horizontal pleiotropy was not present in this study. CONCLUSIONS: There exists a suggestive causal association between increased water intake and decreased risk of colorectal cancer, while ω-3 PUFA intake are suggestive linked to the increased risk of colorectal cancer.

Experience of diet in patients with inflammatory bowel disease: A thematic synthesis of qualitative studies.

AIM: To synthesise the dietary expesriences of patients with inflammatory bowel disease by reviewing relevant qualitative studies. BACKGROUND: Diet plays a crucial role in the development and progression of inflammatory bowel disease (IBD). There is no specific diet that can be recommended for all patients. We conducted a synthesis of qualitative studies to gain a comprehensive understanding of the dietary management experience of patients with IBD, aiming to provide better dietary guidance in the future. DESIGN: A qualitative synthesis was conducted following the Thomas and Harden method and reported following the ENTREQ statement. METHODS: Qualitative studies were systematically searched in five electronic databases: PubMed, PsycINFO, Embase, CINAHL, and Web of Science. There was no time limit for publication, and all database searches were up to 10 May, 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument was utilised to appraise the quality of the included studies. Data for inclusion in articles were extracted and analysed using a thematic synthesis method. RESULTS: Six studies involving 119 patients were eventually included. The studies were conducted in six different countries. Four major themes were identified: the diet of patients with IBD is completely different from the normal one; manage symptoms and live with the disease by modifying diet; psychological adjustment to eating (be frustrated; worried and afraid; feel ashamed; growth and resilience); barriers and challenges (barriers from perceived social support; conflicts between diet and nutrition; challenges from food hedonism and cravings). CONCLUSIONS: Patients with IBD highlighted the distinction between their diet and the normal diet. Dietary modifications were used as a way to manage symptoms and live with the disease. In addition to physical symptoms, patients experienced diet-related psychological changes. Dietary modifications in patients with IBD encounters difficulties and challenges, necessitating prompt guidance and intervention. (1) The implementation of dietary modifications in patients with IBD encounters numerous obstacles and complexities, necessitating prompt guidance and intervention. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REGISTRATION: The protocol was registered with PROSPERO (CRD42023391545).

Whole brain inputs to major descending pathways of the anterior lateral motor cortex.

The anterior lateral motor cortex (ALM) is critical to subsequent correct movements and plays a vital role in predicting specific future movements. Different descending pathways of the ALM are preferentially involved in different roles in movements. However, the circuit function mechanisms of these different pathways may be concealed in the anatomy circuit. Clarifying the anatomy inputs of these pathways should provide some helpful information for elucidating these function mechanisms. Here, we used a retrograde trans-synaptic rabies virus to systematically generate, analyze, and compare whole brain maps of inputs to the thalamus (TH)-, medulla oblongata (Med)-, superior colliculus (SC)-, and pontine nucleus (Pons)-projecting ALM neurons in C57BL/6J mice. Fifty-nine separate regions from nine major brain areas projecting to the descending pathways of the ALM were identified. Brain-wide quantitative analyses revealed identical whole brain input patterns between these descending pathways. Most inputs to the pathways originated from the ipsilateral side of the brain, with most innervations provided by the cortex and TH. The contralateral side of the brain also sent sparse projections, but these were rare, emanating only from the cortex and cerebellum. Nevertheless, the inputs received by TH-, Med-, SC-, and Pons-projecting ALM neurons had different weights, potentially laying an anatomical foundation for understanding the diverse functions of well-defined descending pathways of the ALM. Our findings provide anatomical information to help elucidate the precise connections and diverse functions of the ALM.NEW & NOTEWORTHY Distinct descending pathways of anterior lateral motor cortex (ALM) share common inputs. These inputs are with varied weights. Most inputs were from the ipsilateral side of brain. Preferential inputs were provided by cortex and thalamus (TH).

Nitrogen-Doped and Sulfonated Carbon Dots as a Multifunctional Additive to Realize Highly Reversible Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) using the Zn metal anode have been considered as one of the next-generation commercial batteries with high security, robust capacity, and low price. However, parasitic reactions, notorious dendrites and limited lifespan still hamper their practical applications. Herein, an eco-friendly nitrogen-doped and sulfonated carbon dots (NSCDs) is designed as a multifunctional additive for the cheap aqueous ZnSO4 electrolyte, which can overcome the above difficulties effectively. The abundant polar groups (-COOH, -OH, -NH2 , and -SO3 H) on the CDs surfaces can regulate the solvation structure of Zn2+ through decreasing the coordinated active H2 O molecules, and thus redistribute Zn2+ deposition to avoid side reactions. Some of the negatively charged NSCDs are adsorbed on Zn anode surface to isolate the H2 O/SO4 2- corrosion through the electrostatic shielding effect. The synergistic effect of the doped nitrogen species and the surface sulfonic groups can induce a uniform electrolyte flux and a homogeneous Zn plating with a (002) texture. As a result, the excellent cycle life (4000 h) and Coulombic efficiency (99.5%) of the optimized ZIBs are realized in typical ZnSO4 electrolytes with only 0.1 mg mL-1 of NSCDs additive.

Brain regions susceptible to alpha-synuclein spreading.

The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson's disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.

Effects of High-Definition Transcranial Direct Current Stimulation Targeting the Anterior Cingulate Cortex on the Pain Thresholds: A Randomized Controlled Trial.

BACKGROUND: The majority of existing clinical studies used active transcranial direct current stimulation (tDCS) over superficial areas of the pain neuromatrix to regulate pain, with conflicting results. Few studies have investigated the effect of tDCS on pain thresholds by focusing on targets in deep parts of the pain neuromatrix. METHODS: This study applied a single session of high-definition tDCS (HD-tDCS) targeting the anterior cingulate cortex (ACC) and used a parallel and sham-controlled design to compare the antinociceptive effects in healthy individuals by assessing changes in pain thresholds. Sixty-six female individuals (mean age, 20.5 ± 2.4 years) were randomly allocated into the anodal, cathodal, or sham HD-tDCS groups. The primary outcome of the study was pain thresholds (pressure pain threshold, heat pain threshold, and cold pain threshold), which were evaluated before and after stimulation through the use of quantitative sensory tests. RESULTS: Only cathodal HD-tDCS targeting the ACC significantly increased heat pain threshold (P < 0.05) and pressure pain threshold (P < 0.01) in healthy individuals compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain threshold. Furthermore, no statistically significant difference was found in pain thresholds between anodal and sham HD-tDCS (P > 0.38). Independent of HD-tDCS protocols, the positive and negative affective schedule scores were decreased immediately after stimulation compared with baseline. CONCLUSIONS: The present study has found that cathodal HD-tDCS targeting the ACC provided a strong antinociceptive effect (increase in pain threshold), demonstrating a positive biological effect of HD-tDCS.

Antiepilepticus Effects of Tetrahedral Framework Nucleic Acid via Inhibition of Gliosis-Induced Downregulation of Glutamine Synthetase and Increased AMPAR Internalization in the Postsynaptic Membrane.

More than 15 million out of 70 million patients worldwide do not respond to available antiepilepticus drugs (AEDs). With the emergence of nanomedicine, nanomaterials are increasingly being used to treat many diseases. Here, we report that tetrahedral framework nucleic acid (tFNA), an assembled nucleic acid nanoparticle, showed an excellent ability to the cross blood-brain barrier (BBB) to inhibit M1 microglial activation and A1 reactive astrogliosis in the hippocampus of mice after status epilepticus. Furthermore, tFNA inhibited the downregulation of glutamine synthetase by alleviating oxidative stress in reactive astrocytes and subsequently reduced glutamate accumulation and glutamate-mediated neuronal hyperexcitability. Meanwhile, tFNA promotes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization in the postsynaptic membrane by regulating AMPAR endocytosis, which contributed to reduced calcium influx and ultimately reduced hyperexcitability and spontaneous epilepticus spike frequencies. These findings demonstrated tFNA as a potential AED and that nucleic acid material may be a new direction for the treatment of epilepsy.

Nomogram for predicting occurrence of synchronous liver metastasis in colorectal cancer: a single-center retrospective study based on pathological factors.

PURPOSE: The purpose of this study was to explore the risk factors for synchronous liver metastasis (LM) of colorectal cancer (CRC) and to construct a nomogram for predicting the occurrence of synchronous LM based on baseline and pathological information. METHODS: The baseline and pathological information of 3190 CRC patients were enrolled in the study from the Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University between 2012 and 2020. All patients were divided into development and validation cohorts with the 1:1 ratio. The characters of LM and none-LM patients in newly diagnosed colorectal cancer were utilized to explore the risk factors for synchronous LM with the univariate and multivariate logistic regression analyses. A predictive nomogram was constructed by using an R tool. In addition, receiver operating characteristic (ROC) curves was calculated to describe the discriminability of the nomogram. A calibration curve was plotted to compare the predicted and observed results of the nomogram. Decision-making curve analysis (DCA) was used to evaluate the clinical effect of nomogram. RESULTS: The nomogram consisted of six features including tumor site, vascular invasion (VI), T stage, N stage, preoperative CEA, and CA-199 level. ROC curves for the LM nomogram indicated good discrimination in the development (AUC = 0.885, 95% CI 0.854-0.916) and validation cohort (AUC = 0.857, 95% CI 0.821-0.893). The calibration curve showed that the prediction results of the nomogram were in good agreement with the actual observation results. Moreover, the DCA curves determined the clinical application value of predictive nomogram. CONCLUSIONS: The pathologic-based nomogram could help clinicians to predict the occurrence of synchronous LM in postoperative CRC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

Long-term oncologic outcomes of natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of rectal cancer: a propensity-score matching study.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. METHODS: From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. RESULTS: From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P < 0.001), lower rate of postoperative complications (5.7% vs 15.5%, P = 0.020), more satisfaction with body image (P = 0.001) and cosmesis (P < 0.001) postoperatively. The NOSES group had a higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between the two groups. CONCLUSION: NOSES could be a safe and reliable technique for radical resection of rectal cancer, with better short-term outcomes than conventional laparoscopy, while long-term survival is not significantly different from that of conventional laparoscopic surgery.

Sulfur [18F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis.

The lack of efficient [18F]fluorination processes and target-specific organofluorine chemotypes remains the major challenge of fluorine-18 positron emission tomography (PET). We report here an ultrafast isotopic exchange method for the radiosynthesis of novel PET agent aryl [18F]fluorosulfate enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully automated 18F-radiolabeling of 25 structurally and functionally diverse aryl fluorosulfates with excellent radiochemical yield (83-100%, median 98%) and high molar activity (280 GBq µmol-1) at room temperature in 30 s. The purification of radiotracers requires no time-consuming HPLC but rather a simple cartridge filtration. We further demonstrate the imaging application of a rationally designed poly(ADP-ribose) polymerase 1 (PARP1)-targeting aryl [18F]fluorosulfate by probing subcutaneous tumors in vivo.

Orthogonal test design for optimizing culture medium for in vitro pollen germination of interspecific oil tea hybrids.

Oil Tea (Camellia oleifera) is an important woody edible oil plant in China. Oil Tea suffers from low rate of fruit set during production, which is related to poor pollination and fertilization. Pollen vigor is directly related to pollination and fertilization. Using the interspecific hybrid Y3 (C. grijsii × C. oleifera) as plant material, we studied the effects of sucrose, H3BO3, MgSO4, and IAA on pollen germination using an orthogonal design to determine the best culture medium. Results indicated that pollen germination rates were significantly affected by medium components and ranged from 29.13% to 56.84%. Pollen tube length was the longest in the T5 medium surpassing the control group by 489.36 µm. MgSO4 turned out to be the most important germination medium component having great effect on the pollen germination rate. The optimal culture medium to promote pollen tube growth of Oil Tea Y3 was: 1% agar, 150 g·L-1 sucrose, 0.15 g·L-1 H3BO3, 0.07 g·L-1 MgSO4, and 0.01 g·L-1 IAA. The results of this paper may provide information for foliar application of Mg and IAA, which can improve pollen tube growth of Oil Tea in practice.

Meeting organometallic chemistry with drug discovery: CH activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity.

A diverse library of new ring system 12H-indazolo[2,1-a]cinnolin-12-ones have been synthesized efficiently via Ru (II) and Rh (III) catalyzed tandem CH alkylation/[4 + 2] annulation with diazo compounds in high to excellent yields. For the first time, we evaluated the biological activity of these compounds with this new skeleton and found some compounds exhibited high cytotoxic activity against human PC-3 and PANC-1 tumor cell lines with nanomolar IC50. Among them, the most potent compound 36 showed broad-spectrum cytotoxic activities against a series of human tumor cell lines derived from different organs (IC50 ~ 41 to 197 nM). Moreover, preliminary mechanistic studies indicated that 36 could inhibit the colony formation, cause cell cycle arrest and induce apoptosis of PC-3 cancer cells in a dose-dependent manner. Further intracellular mechanisms investigation found that 36 treatments could dose-dependently decrease the levels of caspase-3 and PARP and up-regulate the level of cleaved PARP. These results suggested that 36 is a novel compound with good potential in the treatment of human cancers and worthy of further investigation.

A Chemistry for Incorporation of Selenium into DNA-Encoded Libraries.

Conventional direct C-H selenylation suffers from simple selenation with limited atom economy and complicated reaction system. In this work, we designed benzoselenazolone as a novel bifunctional selenide reagent for both off- and on-DNA C-H selenylation under rhodium(III) catalysis. We show that using benzoselenazolone allowed production of a series of selenylation products containing an adjacent aminoacyl group in a fast and efficient way, with high atom economy. The synthetic application of this method was demonstrated by taking advantage of the amide functionality as a nucleophile, directing group, and amide coupling partner. This work shows great potential in facilitating rapid construction of selenium-containing DNA-encoded chemical libraries (SeDELs), and lays the foundation for the development of selenium-containing drugs.

The ARF7 and ARF19 Transcription Factors Positively Regulate PHOSPHATE STARVATION RESPONSE1 in Arabidopsis Roots.

PHOSPHATE STARVATION RESPONSE1 (PHR1) is a key regulatory component of the response to phosphate (Pi) starvation. However, the regulation of PHR1 in this response remains poorly understood. Here, we report that PHR1 is a target of the transcription factors AUXIN RESPONSE FACTOR7 (ARF7) and ARF19 and is positively regulated by auxin signaling in Arabidopsis (Arabidopsis thaliana) roots. PHR1 expression was induced by exogenous auxin and suppressed by auxin transport inhibitors in Arabidopsis roots. In the PHR1 promoter, three auxin-response elements, which are bound directly by ARF7 and ARF19, were shown to be essential for PHR1 expression. The arf7, arf19, and arf7 arf19 mutants showed down-regulated expression of PHR1 and downstream Pi starvation-induced genes in roots; they also exhibited defective Pi uptake in roots and overaccumulation of anthocyanin in shoots. The induction of lateral root formation in response to low Pi and to exogenous auxin was decreased in the phr1 mutant, whereas the expression of LATERAL ORGAN BOUNDARIES-DOMAIN16 (LBD16) and LBD29 was not changed significantly. PHR1 acted independently of LBD16 and LBD29 in the regulation of lateral root formation in response to low Pi. Under low-Pi conditions, lateral root impairment in the arf7 arf19 mutant was partially rescued by constitutive expression of PHR1, demonstrating that reduced PHR1 expression contributed to the arf7 arf19 phenotype. In addition to PHR1, other genes encoding MYB-CC members also were targets of ARF7 and ARF19. Our work thus reveals a mechanism coordinating auxin signaling and the PHR1 regulon in Arabidopsis responses to Pi deficiency.

Synthesis of N-Acyl Sulfamates from Fluorosulfonates and Potassium Trimethylsilyloxyl Imidates.

An efficient and operationally simple method for the synthesis of N-acyl sulfamates from fluorosulfonates and potassium trimethylsilyloxyl imidates as amide precursor is reported. This approach showed broad substrate scope, mild and base-free reaction conditions, short reaction time, and high to excellent yields. Notably, we demonstrated the power of this reaction in the rapid late-stage functionalization of three complex phenol-containing bioactive molecules. Given the prevalence of phenol-containing drugs and building blocks, this method is applicable toward a diversity-oriented drug discovery.

Diagnostics and Treatments of Iron-Related CNS Diseases.

Iron has been proposed to be responsible for neuronal loss in several diseases of the central nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Friedreich's ataxia (FRDA), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS). In many diseases, abnormal accumulation of brain iron in disease-affected area has been observed, without clear knowledge of the contribution of iron overload to pathogenesis. Recent evidences implicate that key proteins involved in the disease pathogenesis may also participate in cellular iron metabolism, suggesting that the imbalance of brain iron homeostasis is associated with the diseases. Considering the complicated regulation of iron homeostasis within the brain, a thorough understanding of the molecular events leading to this phenotype is still to be investigated. However, current understanding has already provided the basis for the diagnosis and treatment of iron-related CNS diseases, which will be reviewed here.

Constructing Mononuclear Palladium Catalysts by Precoordination/Solvothermal Polymerization: Recyclable Catalyst for Regioselective Oxidative Heck Reactions.

Heterogeneous, metal, single-site catalysts often exhibit higher catalytic performance than other catalysts because of their maximized atom efficiency of 100 %. Reported herein is a precoordination/solvothermal polymerization strategy to fabricate a stable mononuclear Pd-metalized porous organic polymer catalyst (Pd@POP). Pd@POP was easy to use in regioselective organic reactions because the internal structure of this Pd@POP can be easily modified. The catalyst was used to solve the intractable regioselectivity problems of Heck reactions. Pd@POP-9 can efficiently activate the ends of olefins, thereby leading to high selectivity for substitution at the external position. To understand the reason underlying the high selectivity and activity of the catalyst, the systemic characterization of Pd@POP-9 and density-functional theory calculations were conducted. This Heck reaction is the first to be catalyzed by a recyclable mononuclear metal catalyst with unprecedented catalytic activity and regioselectivity.

Functionality-Independent DNA Encoding of Complex Natural Products.

DNA encoded chemical libraries (DELs) link the powers of genetics and chemical synthesis via combinatorial optimization. Through combinatorial chemistry, DELs can grow to the unprecedented size of billions to trillions. To take full advantage of the DEL approach, linking the power of genetics directly to chemical structures would offer even greater diversity in a finite chemical world. Natural products have evolved an incredible structural diversity along with their biological evolution. Herein, we used traditional Chinese medicines (TCMs) as examples in a late-stage modification toolbox approach to annotate these complex organic compounds with amplifiable DNA barcodes, which could be easily incorporated into a DEL. The method of end-products labeling also generates a cluster of isomers with a single DNA tag at different sites. These isomers provide an additional spatial diversity for multiple accessible pockets of targeted proteins. Notably, a novel PARP1 inhibitor from TCM has been identified from the natural products enriched DEL (nDEL).