Is Transcranial Direct Current Stimulation Effective for Cognitive Dysfunction in Substance Use Disorders? A Systematic Review.

Patients with substance use disorders (SUDs) often suffer from cognitive dysfunction (CD), affecting their quality of life and daily functioning. Current treatments, including pharmacotherapy and psychotherapy, have limited efficacy and notable side effects. Transcranial direct current stimulation (tDCS), a non-invasive technique that modulates cortical activity, shows promise in improving cognitive function with minimal side effects and low cost, and could potentially serve as a valuable adjunct to existing therapies. This systematic review aims to evaluate the literature on the effectiveness of tDCS for CD in SUD patients to inform clinical practice and future research. Following PRISMA guidelines, the review includes studies that used tDCS for SUD-related CD. The criteria for inclusion encompassed participants aged 18 and older with a diagnosis of SUD, the use of tDCS (either conventional or high-definition), control groups receiving sham stimulation or no intervention, and cognitive outcome measures for substance-related cognitive function using validated tools. Databases searched were Ovid MEDLINE, PubMed, Web of Science, Embase, Scopus, and PsycINFO, with specific keywords. Twenty-two studies met the criteria, suggesting tDCS can improve cognitive functions in SUD patients, though results varied. Effectiveness may depend on the brain area targeted, stimulation parameters, task requirements, and individual differences. tDCS shows potential in treating SUD-related CD, but further research is needed to optimize stimulation protocols and address study variability. Future studies should use functional magnetic resonance imaging to explore the brain mechanisms by which tDCS improves cognitive function in SUDs and focus on larger, long-term trials to confirm efficacy and refine tDCS treatment parameters.

Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).

Impact of o-aryl halogen effects on ethylene polymerization: steric vs. electronic effects.

Ligand steric hindrance and electronic effects play a crucial role in late-transition metal-catalyzed olefin polymerization. In this research, a series of o-aryl halogenated α-diimine ligands bearing bulky dibenzhydryl substituents, along with their corresponding nickel catalysts, have been synthesized and thoroughly characterized. The nickel catalysts demonstrated very high activity in ethylene polymerization, achieving a high rate of up to 107 g mol-1 h-1. The produced polyethylenes displayed a broad spectrum of molecular weights (12.2-871.7 kg mol-1) but maintained consistent branching densities (50-82/1000 C) when polymerized at a fixed temperature with different nickel catalysts. Notably, the polymerization temperature has a significant influence on both the molecular weight and branching density of the resulting polyethylene. Higher temperatures led to the formation of polyethylenes with lower molecular weights and increased branching densities. Interestingly, the o-aryl halogens significantly impact the molecular weight of the polyethylene. The size of the halogen substituents primarily determines the molecular weight of the polyethylene. However, in terms of branching density, the steric and electronic effects of these substituents appear to counteract each other. In addition, the branched high molecular weight polyethylenes from the bromine and chlorine substituted nickel catalysts are excellent polyethylene thermoplastic elastomers with high strain at break values (688-2478%) and high strain recovery values (42-62%).

Flexible Axial Shielding Strategy for Improving Ethylene (Co)polymerization with 8-Cycloalkylnaphthyl α-Diimine Catalysts.

8-aryl or alkyl-naphthyl substituents are widely used as an effective axial shielding strategy for the suppression of chain transfer in late-transition metal-catalyzed ethylene (co)polymerization to yield high molecular weight polyethylene and copolymers. In this study, two 8-cycloalkylnaphthyl acenaphthene-based α-diimine ligands and the corresponding four nickel and palladium complexes were designed and synthesized to explore the effect of axial flexible shielding on ethylene (co)polymerization. In ethylene polymerization, the nickel complexes displayed high activities (up to 1.99 × 106 g mol-1 h-1) and generated lightly branched (34-54/1000 C) polyethylenes with high molecular weights (up to Mn = 1075 kg/mol), whereas the corresponding palladium complexes exhibited moderate activities (level of 104 g mol-1 h-1), producing highly branched (111-125/1000 C) polyethylenes with high molecular weights (up to Mn = 37.6 kg/mol). Highly branched (110-123/1000 C) E-MA copolymers with moderate insertion ratios (1.97-5.56 mol %) were produced by these palladium complexes in ethylene/methyl acrylate (MA) copolymerization. In addition, the size of the 8-cycloalkyl ring in these α-diimine catalysts strongly influences the ethylene (co)polymerization. Compared to cyclopentyl groups, cyclohexyl groups are more effective in suppressing chain transfer reactions in the polymerization of ethylene and the copolymerization of ethylene and MA, leading to higher molecular weight polyethylene and E-MA copolymers. Most interestingly, compared to the reported rigid planar 8-arylnaphthyl catalysts, the flexible 8-cyclohexylnaphthyl catalysts exhibited higher activity and produced higher molecular weight polyethylene in ethylene polymerization. Moreover, in nickel-catalyzed ethylene polymerization, the cyclohexyl catalyst produced significantly reduced branched polyethylene, while in palladium-catalyzed ethylene (co)polymerization, the cyclohexyl catalyst produced more highly branched polyethylene and copolymers. In contrast to the previously reported flexible 8-butylnaphthyl nickel catalysts, the 8-cycloalkylnaphthyl catalysts reported in this work yielded polyethylene with narrow unimodal molecular weight distributions.

Direct Synthesis of Polyethylene Thermoplastic Elastomers Using Hybrid Bulky Acenaphthene-Based α-Diimine Ni(II) Catalysts.

Recently, polyolefin thermoplastic elastomers can be obtained directly using ethylene as a single feedstock via α-diimine nickel-catalyzed ethylene chain walking polymerization. Here, a new range of bulky acenaphthene-based α-diimine nickel complexes with hybrid o-phenyl and -diarylmethyl anilines were constructed and applied to ethylene polymerization. All the nickel complexes under the activation of excess Et2AlCl exhibited good activity (level of 106 g mol-1 h-1) and produced polyethylene with high molecular weight (75.6-352.4 kg/mol) as well as proper branching densities (55-77/1000C). All the branched polyethylenes obtained exhibited high strain (704-1097%) and moderate to high stress (7-25 MPa) at break values. Most interestingly, the polyethylene produced by the methoxy-substituted nickel complex exhibited significantly lower molecular weights and branching densities, as well as significantly poorer strain recovery values (48% vs. 78-80%) than those by the other two complexes under the same conditions.

Effects of aquatic exercise on the improvement of lower-extremity motor function and quality of life in patients with Parkinson's disease: A meta-analysis.

Objective: To systematically evaluate the effect of aquatic exercise interventions on the improvement of lower-extremity motor function and quality of life in patients with Parkinson's disease. Methods: Two researchers independently searched the literature using the PubMed, Web of Science, Embase, and Cochrane Library databases. The search period was from the establishment of the database to December 2021. The subject heading search included "hydrotherapy," "hydro therapies," "hydro therapeutics," "water therapy," "aquatic exercise therapy," "aquatic therapy," "water-based exercise," "Parkinson," "Parkinson disease," "Parkinson's disease," "Parkinson's syndrome," "primary Parkinsonism," "paralysis agitans," and "randomized controlled trial (RCT)." Result: A total of 698 articles were retrieved from the four databases by searching for subject headings, and 10 RCT articles were finally included. The balance ability of aquatic exercise in patients with Parkinson's disease (weighted mean differences [WMD] = 2.234, 95% CI: 1.112-3.357, Z = 3.9, p < 0.01), walking ability (WMD = -0.911, 95% CI: -1.581 to -0.241, Z = 2.67, p < 0.01), and quality of life (WMD = -5.057, 95% CI: -9.610 to -0.504, Z = 2.18, p = 0.029) were improved, but there was no significant difference in motor function (WMD = -0.328, 95% CI: -1.781 to 1.125, Z = 0.44, p = 0.658). Conclusion: Compared with conventional rehabilitation therapy, aquatic exercise can effectively improve balance, walking ability, and quality of life in patients with Parkinson's disease. However, it had no obvious effect on improving motor function. This study was limited by the number and quality of the included studies, and more high-quality studies are needed to verify this. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022365103.

Direct Synthesis of Chain-End Toluene Functionalized Hyperbranched Ethylene Oligomers.

Chain-end functionalized polymers play an important role in the field of building complex macromolecular structures. In this study, we have synthesized and characterized four dibenzhydryl iminopyridine Ni(II) complexes bearing remote flexible substituents (Et and n-Bu) to provide hyperbranched ethylene oligomers in ethylene oligomerization with moderate to good activities. Most notably, toluene-end-functionalized hyperbranched ethylene oligomers were obtained under elevated temperature conditions and validated by NMR. The tandem catalysis of ethylene oligomerization and the subsequent Friedel-Crafts addition of the resulting unsaturated products to toluene molecules was proposed as the cause of the observed phenomenon.

Ethylene (co) oligomerization using iminopyridyl Ni(II) and Pd(II) complexes bearing benzocycloalkyl moieties to access hyperbranched ethylene oligomers and ethylene-MA co-oligomers.

Hyperbranched ethylene oligomers and polar functionalized co-oligomers synthesized via ethylene chain walking (co) oligomerization is a very attractive strategy. In this study, a series of dibenzhydryl iminopyridyl ligands with benzocycloalkyl and naphthyl moieties and the corresponding Ni(II) and Pd(II) complexes were synthesized and characterized. The Ni(II) complexes were highly effective in ethylene oligomerization and ethylene oligomers with hyperbranched microstructures were generated from this system. The corresponding Pd(II) complexes showed moderate oligomerization activities in ethylene oligomerization and hyperbranched ethylene oligomers were also yielded from the system. More significantly, the Pd(II) complexes can also effectively promote the co-oligomerization of ethylene with methyl acrylate (MA) to obtain hyperbranched polar functionalized ethylene-MA co-oligomers. The reaction temperature, catalyst ligand structure and metal type all have significant effects on ethylene (co) oligomerization with respect to catalytic activity, molecular weight and topology of the oligomers.

Synthesis of High-Molecular-Weight Branched Polyethylene Using a Hybrid "Sandwich" Pyridine-Imine Ni(II) Catalyst.

Most pyridine-imine Ni(II) and Pd(II) catalysts tend to yield low-molecular-weight polyethylene and ethylene-based copolymers in olefin insertion polymerization, as the unilateral axial steric structure of such complexes often cannot provide effective shielding of the metal center. In this study, we synthesized a series of hybrid "semi-sandwich" and "sandwich" type pyridine-imine Ni(II) complexes by incorporating diarylmethyl or dibenzosuberyl groups onto 8-aryl-naphthyl motif. The as-prepared Ni(II) complexes afforded highly branched polyethylene with high molecular weights (level of 105 g/mol), and moderate activities (level of 105 g/(molh)) in ethylene polymerization. Most interestingly, compared to "semi-sandwich" Ni(II) complexes bearing (2-diarylmethyl-8-aryl)naphthyl units, the "full-sandwich" counterpart containing (2-dibenzosuberyl-8-aryl)naphthyl motif was able to produce higher-molecular-weight polyethylene with higher branching density. In addition, the effect of remote non-conjugated electronic substituents in diarylmethyl groups of the Ni(II) system was also observed in ethylene polymerization.

Exploring the Relationship between the Polyethylene Microstructure and Spatial Structure of α-Diimine Pd(II) Catalysts via a Hybrid Steric Strategy.

The branching density of polyethylene generated in the α-diimine Pd(II) system is usually very high, largely independent of simple ligand modifications with steric or electronic perturbations, or the polymerization conditions. In this study, we designed and synthesized a class of bulky hybrid α-diimine Pd(II) catalysts combining ortho-diarylmethyl and ortho-phenyl moieties to explore the relationship between the polyethylene microstructure and the spatial structure of catalysts. In ethylene polymerization, the hybrid α-diimine Pd(II) catalysts exhibited high activities (well above 105 g·mol-1·h-1) and yielded highly branched (90-110/1000C) polyethylenes with high molecular weights (up to 278.3 kg/mol). Compared with the two corresponding symmetrical ortho-diarylmethyl-based or ortho-phenyl-based Pd(II) catalysts, the hybrid catalysts generated polyethylene of significantly higher branching densities (92 vs 28-34/1000C) in marked higher activities. Similar phenomena are also observed in the copolymerization of ethylene with polar monomers. Moreover, the hybrid Pd(II) catalysts can more efficiently promote the copolymerization of ethylene with various polar monomers in comparison to the corresponding symmetrical catalysts. The more open spatial environment around the metal center by using a hybrid steric strategy was proposed to be responsible for above advantages.

Facile Synthesis of Hyperbranched Ethylene Oligomers and Ethylene/Methyl Acrylate Co-oligomers with Different Microscopic Chain Architectures.

Low-molecular-weight (MW) ethylene oligomers with hyperbranched microstructures are often difficult to be synthesized by traditional catalytic processes. In this study, a series of N-terphenyl iminopyridyl ligands and the corresponding Pd(II) and Ni(II) complexes bearing remote conjugated substituents with different electronic effects (H, Me, F, Cl, and tBu) were synthesized in a simple and efficient way. These Pd(II) and Ni(II) complexes were highly effective in the ethylene oligomerization and co-oligomerization with methyl acrylate (MA). Low-MW ethylene oligomers with hyperbranched microstructures were generated using the iminopyridyl Pd(II) and Ni(II) complexes in ethylene oligomerization. More importantly, polar functionalized ethylene-MA co-oligomers with low MWs and varying incorporation ratios were generated via ethylene and MA co-oligomerization using the Pd(II) complexes. Most notably, these ethylene oligomers obtained by different metal species showed a significant difference in microscopic chain architectures. The remote conjugated electron effect showed little effect on the polymerization parameters of the iminopyridyl system, which is very different from those of the salicylaldiminato system.

Direct Synthesis of Partially Chain-Straightened Propylene Oligomers and P-MA Co-Oligomers Using Axially Flexible Shielded Iminopyridyl Palladium Complexes.

In this study, a series of partially chain-straightened propylene oligomers and functional propylene−methyl acrylate (P-MA) co-oligomers were synthesized with 8-alkyl-iminopyridyl Pd(II) catalysts. The molecular weight and polar monomer incorporation ratio could be tuned by using Pd(II) catalysts with various 8-alkyl-naphthyl substituents (8-alkyl: H, Me, and n-Bu). In propylene oligomerization, all the 8-alkyl-iminopyridyl Pd(II) catalysts convert propylene to partially chain-straightened (119−136/1000 C) oligomers with low molecular weights (0.3−1.5 kg/mol). Among the catalysts, Pd1 with non-substituent (H) on the ligand showed the highest activity of 5.4 × 104 g/((mol of Pd) h), generating oligomers with the lowest molecular weight (Mn: 0.3 kg/mol). Moreover, polar-functionalized propylene-MA co-oligomers with very high incorporation ratios (22.8−36.5 mol %) could be obtained in the copolymerization using these 8-alkyl-iminopyridyl Pd(II) catalysts. Additionally, Pd1 exhibited the best performance in propylene-MA copolymerization as it displayed the highest MA incorporation ratio of up to 36.5 mol%. All the three catalysts are capable of generating partially chain-straightened P-MA co-oligomers and the activities decrease gradually while the molecular weight increases with the increasing steric hindrance of the alkyl substituent (H < Me < n-Bu). Compared to Pd4 with the rigid 8-aryl substituent, the flexible 8-alkyl-iminopyridyl Pd(II) catalysts (Pd1-3) not only showed much higher activities in the propylene oligomerization, but also yielded P-MA co-oligomers with significantly higher incorporation ratios in the propylene co-oligomerization.

Flexible "Sandwich" (8-Alkylnaphthyl α-Diimine) Catalysts in Insertion Polymerization.

8-Arylnaphthyl substituents are privileged motifs frequently integrated into late-transition-metal catalysts, endowing them with an ability to retard chain transfer in ethylene polymerization. In this contribution, we disclose a sort of novel α-diiminenickel and -palladium complexes containing flexible 8-alkylnaphthyl in lieu of rigid 8-arylnaphthyl and their catalytic performance in ethylene polymerization. An interesting feature of these 8-alkylnaphthyl-substituted α-(diimine)PdMeCl complexes is that they present as a mixture of syn and anti isomers (syn:anti = ca. 1:1 ratio, determined by 1H and 13C NMR spectroscopy). In ethylene polymerization, these nickel complexes displayed high activity (up to 3.37 × 106 g mol-1 h-1) and generated branched polyethylenes with broad or bimodal molecular weight distributions (4.6-29.3), while the corresponding palladium complexes exhibited moderate activity, producing highly branched polyethylenes with unimodal and narrow molecular weight distributions (<1.8). In ethylene (E)/methyl acrylate (MA) copolymerization, highly branched E-MA copolymers with considerable MA incorporations were achieved by these palladium complexes. Most interestingly, compared to rigid 8-arylnaphthyl-substituted α-diiminenickel and -palladium complexes, the flexible 8-alkylnaphthyl ones showed significantly improved activity and generated lower or comparable molecular weight polyethylenes or E-MA copolymers.

Efficient Suppression of Chain Transfer and Branching via Cs -Type Shielding in a Neutral Nickel(II) Catalyst.

An effective shielding of both apical positions of a neutral NiII active site is achieved by dibenzosuberyl groups, both attached via the same donors' N-aryl group in a Cs -type arrangement. The key aniline building block is accessible in a single step from commercially available dibenzosuberol. This shielding approach suppresses chain transfer and branch formation to such an extent that ultrahigh molecular weight polyethylenes (5×106  g mol-1 ) are accessible, with a strictly linear microstructure (<0.1 branches/1000C). Key features of this highly active (4.3×105  turnovers h-1 ) catalyst are an exceptionally facile preparation, thermal robustness (up to 90 °C polymerization temperature), ability for living polymerization and compatibility with THF as a polar reaction medium.

A Self-Supporting Strategy for Gas-Phase and Slurry-Phase Ethylene Polymerization using Late-Transition-Metal Catalysts.

The polyolefin industry is dominated by gas-phase and slurry-phase polymerization using heterogeneous catalysts. In contrast, academic research is focused on homogeneous systems, especially for late-transition-metal catalysts. The heterogenization of homogeneous catalysts is a general strategy to provide catalyst solutions for existing industrial polyolefin synthesis. Herein, we report an alternative, potentially general strategy for using homogeneous late-transition-metal catalysts in gas-phase and slurry-phase polymerization. In this self-supporting strategy, catalysts with moderate chain-walking capabilities produced porous polymer supports during gas-phase ethylene polymerization. Chain walking, in which the metal center can move up and down the polymer chain during polymerization, ensures that the metal center can travel along the polymer chain to find suitable sites for ethylene enchainment. This strategy enables simple heterogenization of catalysts on solid supports for slurry-phase polymerization. Most importantly, various branched ultra-high-molecular-weight polyethylenes can be prepared under various polymerization conditions with proper catalyst selection.

Direct Synthesis of Branched Carboxylic Acid Functionalized Poly(1-octene) by α-Diimine Palladium Catalysts.

In this work, we studied propylene polymerization using some α-diimine palladium catalysts with systematically varied ligand sterics. In propylene polymerization, the ligand steric effect exhibits significant variations on the catalytic activity, polymer molecular weight, and branching density. However, the regio control for the polymer microstructure is poor. Furthermore, copolymerization of 1-octene with the highly challenging and biorenewable comonomer acrylic acid was investigated. High copolymer molecular weights and high comonomer incorporation ratios could be achieved in this system. This study provides a novel access for the direct synthesis of branched carboxylic acid functionalized polyolefins.

Direct Synthesis of Functionalized High-Molecular-Weight Polyethylene by Copolymerization of Ethylene with Polar Monomers.

The introduction of even a small amount of polar functional groups into polyolefins could excise great control over important material properties. As the most direct and economic strategy, the transition-metal-catalyzed copolymerization of olefins with polar, functionalized monomers represents one of the biggest challenges in this field. The presence of polar monomers usually dramatically reduces the catalytic activity and copolymer molecular weight (to the level of thousands or even hundreds Da), rendering the copolymerization process and the copolymer materials far from ideal for industrial applications. In this contribution, we demonstrate that these obstacles can be addressed through rational catalyst design. Copolymers with highly linear microstructures, high melting temperatures, and very high molecular weights (close to or above 1 000 000 Da) were generated. The direct synthesis of polar functionalized high-molecular-weight polyethylene was thus achieved.

Synthesis of high molecular weight polyethylene using iminopyridyl nickel catalysts.

A series of iminopyridyl Ni(ii) catalysts containing both the dibenzhydryl and the naphthyl moieties can polymerize ethylene with high activity and high thermal stability, generating polyethylene with a molecular weight of up to one million. In α-olefin polymerization, semicrystalline polymers with high melting temperatures are generated.

Investigations of the Ligand Electronic Effects on α-Diimine Nickel(II) Catalyzed Ethylene Polymerization.

The synthesis and characterization of a series of dibenzhydryl-based α-diimine Ni(II) complexes bearing a range of electron-donating or -withdrawing groups are described. Polymerization with ethylene is investigated in detail, involving the activator effect, influence of polymerization conditions on catalyst activity, thermal stability, polymer molecular weight and melting point. All of these Ni(II) complexes show great activity (up to 6 × 106 g of PE (mol of Ni)-1·h-1), exceptional thermal stability (stable at up to 100 °C) and generate polyethylene with very high molecular weight (Mn up to 1.6 × 106) and very narrow molecular weight distribution. In the dibromo Ni(II) system, the electronic perturbations exhibit little variation on the ethylene polymerization. In the Ni(acac) system, dramatic ligand electronic effects are observed in terms of catalytic activity and polyethylene molecular weight.

Ethylene polymerization by salicylaldimine nickel(II) complexes containing a dibenzhydryl moiety.

The synthesis, characterization and ethylene polymerization properties of a series of salicylaldimine Ni(ii) complexes with a dibenzhydryl moiety are described. These Ni complexes are designed to bear systematically varied electron donating and withdrawing substituents. These complexes are among the most active salicylaldimine Ni(ii) catalysts in ethylene polymerization. Moreover, these complexes demonstrate good thermal stability, maintaining high activity at 80 °C. The polyethylene generated possesses a high molecular weight, moderate branching density and high melting temperature. Surprisingly, the electronic perturbations only exert moderate influence on the ethylene polymerization process despite the covalently close proximity of the electron donating or withdrawing substituents to the metal center. Comparing with the traditional iso-propyl substituted nickel analogue, these new complexes show up to an order of magnitude higher activity, generating polyethylene with much higher molecular weight, similar or slightly lower branching density and much higher melting temperature.