Recent advances in total synthesis of protoberberine and chiral tetrahydroberberine alkaloids.

Covering: Up to 2024Due to the widespread distribution of protoberberine alkaloids (PBs) and tetrahydroberberine alkaloids (THPBs) in nature, coupled with their myriad unique physiological activities, they have garnered considerable attention from medical practitioners. Over the past few decades, synthetic chemists have devised various total synthesis methods to attain these structures, continually expanding reaction pathways to achieve more efficient synthetic strategies. Simultaneously, the chiral construction of THPBs has become a focal point. In this comprehensive review, we categorically summarized the developmental trajectory of the total synthesis of these alkaloids based on the core closure strategies of protoberberine and tetrahydroberberine.

Recent Advances in the Total Synthesis of Spirotryprostatin Alkaloids.

Spirotryprostatin alkaloids, a class of alkaloids with a unique spirocyclic indoledionepiperazine structure, were first extracted from the fermentation broth of Aspergillus fumigatus and have garnered significant attention in the fields of biology and pharmacology. The investigation into the pharmacological potential of this class of alkaloids has unveiled promising applications in drug discovery and development. Notably, certain spirotryprostatin alkaloids have demonstrated remarkable anti-cancer activity, positioning them as potential candidates for anti-tumor drug development. In recent years, organic synthetic chemists have dedicated efforts to devise efficient and viable strategies for the total synthesis of spirotryprostatin alkaloids, aiming to meet the demands within the pharmaceutical domain. The construction of the spiro-C atom within the spirotryprostatin scaffold and the chirality control at the spiro atomic center emerge as pivotal aspects in the synthesis of these compounds. This review categorically delineates the synthesis of spirotryprostatin alkaloids based on the formation mechanism of the spiro-C atom.

Fluorine in the pharmaceutical industry: Synthetic approaches and application of clinically approved fluorine-enriched anti-infectious medications.

The strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular mechanisms. It further outlines the specific effects of fluorination, which contribute to the heightened efficacy of anti-infective therapies. By presenting a comprehensive analysis of current drugs and their developmental pathways, this review underscores the continuing evolution and significance of fluorine in advancing anti-infectious treatment options. The insights offered extend valuable guidance for future drug design and the development of next-generation anti-infectious agents.

Daphmacrimines A-K, Daphniphyllum alkaloids from Daphniphyllum macropodum Miq.

Daphmacrimines A-K (1-11) were isolated from the leaves and stems of Daphniphyllum macropodum Miq. Their structures and stereochemistries were determined by extensive techniques, including HRESIMS, NMR, ECD, IR, and single-crystal X-ray crystallography. Daphmacrimines A-D (1-4) are unprecedented Daphniphyllum alkaloids with a 2-oxazolidinone ring. Daphmacrimine I (9) contains a nitrile group, which is relatively rare in naturally occurring alkaloids. The abilities of daphmacrimines A-D and daphmacrimines G-K to enhance lysosomal biogenesis were evaluated through LysoTracker Red staining. Daphmacrimine K (11) can induce lysosomal biogenesis and promote autophagic flux.

Catalysts of Healing: A Symphony of Synthesis and Clinical Artistry in Small-Molecule Agents for Breast Cancer Alleviation.

Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms of action range from modulating hormone receptor signaling and inhibiting kinase activity, to impeding DNA damage repair mechanisms. Clinical applications of these drugs have resulted in enhanced patient survival rates, reduction in disease recurrence, and improved overall therapeutic indices. Notably, certain molecules have showcased efficacy in drug-resistant breast cancer phenotypes, highlighting their potential in addressing treatment challenges. The evolution and approval of small-molecule drugs have ushered in a new era for breast cancer therapeutics. Their tailored synthetic pathways and defined mechanisms of action have augmented the precision and efficacy of treatment regimens, paving the way for improved patient outcomes in the face of this pervasive malignancy. The present review embarks on a detailed exploration of small-molecule drugs that have secured regulatory approval for breast cancer treatment, emphasizing their clinical applications, synthetic pathways, and distinct mechanisms of action.

Research On Effects Of High Intensity Interval Training On Cardiopulmonary Function In Adolescents

High intensity interval training (HIIT) is now a very exercise attention by society, scholars from all over the world have to look into the training methods. At present, most studies on HIIT in the market compare it with moderate intensity continuous aerobic exercise. From another perspective, this study compares HIIT training with typical Repetition Training (RT) in strength training to study the changes of cardiopulmonary function indicators in adolescents. The aim is to find a more suitable and efficient way for youth sports training, so as to improve their physical fitness level. (AU)

Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance.

Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, the effects of ISO in combination with DEX was conducted on leukemia in vivo and glucocorticoid resistance in vitro. As a result, the combination of the two compounds could efficiently inhibit leukemia progression in mice and reverse DEX resistance in acute lymphoblastic leukemia (ALL) Jurkat cells. Significantly, our findings indicated that c-Myc may be a potential target of ISO, as it is involved in cell cycle arrest and apoptosis by the combination of ISO and DEX in Jurkat cells. Furthermore, western blot analysis revealed that ISO and DEX inhibits the PI3K/Akt/mTOR signaling pathway and promotes the nuclear translocation of glucocorticoid receptor (GR), which activates target genes NR3C1 and TSC22D3, leading to apoptosis in Jurkat cells. Hence, our results suggest that ISO, as a safe and effective food-derived agent, can enhance the anti-leukemia effects of DEX.

Recycling of hazardous jarosite residues based on hydrothermal crystal transformation.

Jarosite [MeFe3(SO4)2(OH)6] is a typical non-ferrous smelting slag produced in the process of iron removal from hydrometallurgical solution, which contains a large number of valuable and toxic metal elements. Treating the complex and hazardous jarosite residue in an economically and environmentally sound way has always been an urgent problem. A novel one-step hydrothermal treatment method was proposed in this paper for recycling of jarosite residues. It can be seen from the XRD and TEM results that jarosite residues could be completely transformed into hematite crystal particles under hydrothermal conditions at temperature above 220℃. Meanwhile, other valuable metal components (such as nickel sulfate hexahydrate) entrained in the residue will be dissolved in the aqueous solution, which can be reused in the hydrometallurgical process. Through phase composition analysis of the hydrothermal process, it is concluded that jarosite was firstly pyrolyzed to generate Fe3+. The obtained Fe3+ was then hydrolyzed to Fe (OH)3, which was transformed into Fe2O3 through dehydration condensation and directional arrangement. Further roasting the hematite particles, the obtained product contained 62.57 % of Fe, but only 0.21 % of S and 0.04 % of As, which meets the requirements of raw materials for iron making. In addition, compared with the current international standard ISO 1248:2006 (E), the obtained hematite particles with nanometer size and single crystal structure can be used as iron oxide red pigment. Overall, the one-step hydrothermal treatment of jarosite residues followed by reduction roasting not only realizes the economic recycling of the metal resources, but also solves the stacking problem of those hazardous residues.

Synthetic approaches and application of clinically approved small-molecule drugs to treat hepatitis.

Hepatitis, a global public health concern, presents a significant burden on healthcare systems worldwide. Particularly, hepatitis B and C are viral infections that can lead to severe liver damage, cirrhosis, and even hepatocellular carcinoma (HCC). The urgency to combat these diseases has driven researchers to explore existing small-molecule drugs as potential therapeutics. This comprehensive review provides a systematic overview of synthetic routes to key antiviral agents used to manage hepatitis. Furthermore, it elucidates the mechanisms of action of these drugs, shedding light on their interference with viral replication and liver disease progression. The review also discusses the clinical applications of these drugs, including their use in combination therapies and various patient populations. By evaluating the synthetic pathways and clinical utility of these drugs, this review not only consolidates current knowledge but also highlights potential future directions for research and drug development in the fight against hepatitis, ultimately contributing to improved patient outcomes and reduced global disease burden.

Iridoid glycosides from Morinda officinalis induce lysosomal biogenesis and promote autophagic flux to attenuate oxidative stress.

Morinda officinalis is a traditional Chinese tonic herb, and have been used in the treatment of multiple diseases. Here, three iridoid glycosides isolated from M. officinalis were evaluated for their roles in the autophagy-lysosomal pathway. All three iridoid glycosides could induce TFEB/TFE3-mediated lysosomal biogenesis and trigger autophagy. Interestingly, they promoted the nuclear import of TFEB/TFE3 without affecting their nuclear export, suggesting their role in the maintenance of lysosomal homeostasis. The results from this study shed light on the identification of autophagy activators from M. officinalis and provide a basis for developing them in the treatment of oxidative stress-involved diseases.

Advances of clinically approved small-molecule drugs for the treatment of non-small cell lung cancer.

Lung cancer continues to pose a significant challenge as a prominent contributor to global cancer-related mortality. Despite the considerable strides made in therapeutic interventions within the past decade, a substantial population of patients diagnosed with non-small cell lung cancer (NSCLC) still face the grim reality of an incurable condition. In the realm of optimal management strategies for individuals afflicted with locally advanced, yet amenable to surgical resection, NSCLC, a therapeutic approach encompassing chemoradiation stands as a fundamental component. Significant strides have been made in the therapeutic landscape of NSCLC during the preceding two decades, facilitating an enhanced comprehension of the underlying disease biology, and mechanisms governing tumor progression, as well as advancements in early detection modalities and multimodal therapeutic interventions. Nevertheless, the overall rates of curative interventions and survival outcomes for NSCLC continue to exhibit a discouragingly low trajectory, particularly in the context of metastatic disease. Hence, the imperative for sustained research endeavors in the realm of novel pharmaceutical agents and combinatorial therapeutic approaches remains paramount, with the overarching objective of broadening the scope of clinical advantages conferred upon a wider demographic of patients, thereby fostering tangible improvements in outcomes pertaining to NSCLC. The primary objective of this review is to provide an all-encompassing examination encompassing the clinical application and synthetic routes of specific drugs, with the explicit aim of disseminating invaluable knowledge that can inform future research and development endeavors focused on NSCLC.

Multi-scale feature fusion for pavement crack detection based on Transformer.

Automated pavement crack image segmentation presents a significant challenge due to the difficulty in detecting slender cracks on complex pavement backgrounds, as well as the significant impact of lighting conditions. In this paper, we propose a novel approach for automated pavement crack detection using a multi-scale feature fusion network based on the Transformer architecture, leveraging an encoding-decoding structure. In the encoding phase, the Transformer is leveraged as a substitute for the convolution operation, which utilizes global modeling to enhance feature extraction capabilities and address long-distance dependence. Then, dilated convolution is employed to increase the receptive field of the feature map while maintaining resolution, thereby further improving context information acquisition. In the decoding phase, the linear layer is employed to adjust the length of feature sequence output by different encoder block, and the multi-scale feature map is obtained after dimension conversion. Detailed information of cracks can be restored by fusing multi-scale features, thereby improving the accuracy of crack detection. Our proposed method achieves an F1 score of 70.84% on the Crack500 dataset and 84.50% on the DeepCrack dataset, which are improvements of 1.42% and 2.07% over the state-of-the-art method, respectively. The experimental results show that the proposed method has higher detection accuracy, better generalization and better crack detection results can be obtained under both high and low brightness conditions.

Recent advance of clinically approved small-molecule drugs for the treatment of myeloid leukemia.

Myeloid leukemia denotes a hematologic malignancy characterized by aberrant proliferation and impaired differentiation of blood progenitor cells within the bone marrow. Despite the availability of several treatment options, the clinical outlook for individuals afflicted with myeloid leukemia continues to be unfavorable, making it a challenging disease to manage. Over the past, substantial endeavors have been dedicated to the identification of novel targets and the advancement of enhanced therapeutic modalities to ameliorate the management of this disease, resulting in the discovery of many clinically approved small-molecule drugs for myeloid leukemia, including histone deacetylase inhibitors, hypomethylating agents, and tyrosine kinase inhibitors. This comprehensive review succinctly presents an up-to-date assessment of the application and synthetic routes of clinically sanctioned small-molecule drugs employed in the treatment of myeloid leukemia. Additionally, it provides a concise exploration of the pertinent challenges and prospects encompassing drug resistance and toxicity. Overall, this review effectively underscores the considerable promise exhibited by clinically endorsed small-molecule drugs in the therapeutic realm of myeloid leukemia, while concurrently shedding light on the prospective avenues that may shape the future landscape of drug development within this domain.

[Main Chemical Components in Atmospheric Precipitation and Their Sources in Xi'an].

In order to understand the current status of main chemical components of atmospheric precipitation in Xi'an, the pH, electrical conductivity, mass concentration of water-soluble ions and heavy metals, wet deposition fluxes, and their sources in precipitation samples in urban and suburban areas of Xi'an in 2019 were studied. The results showed that the pH, conductivity, water-soluble ions, and heavy metals in precipitation in Xi'an in winter were higher than those in other seasons. The main water-soluble ions in precipitation were Ca2+, NH+4, SO2-4, and NO-3, and the sum of these ions accounted for (88.5%±2.8)% of the total ion concentration in urban and suburban areas. The main heavy metals were Zn, Fe, and Zn and Mn; their sum accounted for (54.0%±3)% and (47.0%±8)% of the total metal concentration. The wet deposition fluxes of water-soluble ions in precipitation in urban and suburban areas were (253.2±58.4) mg·(m2·month)-1 and (241.9±61.1) mg·(m2·month)-1, respectively. They showed higher values in winter than those in other seasons. The wet deposition fluxes of heavy metals were (86.2±37.5) mg·(m2·month)-1 and (88.1±37.4) mg·(m2·month)-1, respectively, with little seasonal difference. The source analysis using PMF showed that the water-soluble ions in urban and suburban precipitation mainly came from combustion sources (57.5% and 32.32%), followed by motor vehicles (24.4% and 17.2%) and dust sources (18.1% and 27.0%). The ions in suburban precipitation were also affected by local agriculture (11.1%). Heavy metals in precipitation in urban and suburban areas mainly came from industrial sources (51.8% and 46.7%), and the contribution rate of coal and motor vehicle mixed sources in winter was 10.7% and 6.1% higher than that in summer, respectively.

Vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands for ethylene (co-)polymerization.

Several trivalent and pentavalent vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands were synthesized. These vanadium complexes were identified by elemental analysis, FTIR spectroscopy and NMR. Single crystals of trivalent vanadium complexes V2, V3', and V4 and pentavalent vanadium complexes V5 and V7 were further obtained and identified by X-ray single crystal diffraction. In addition, the catalytic performance of these catalysts was adjusted by controlling the electronic and steric effects of substituents in the ligands. In the presence of diethylaluminium chloride, complexes V5-V7 displayed high activity (up to 82.8 × 106 g molV-1 h-1) and good thermal stability toward ethylene polymerization. In addition, the copolymerization ability of complexes V5-V7 was evaluated, and complexes V5-V7 displayed high activity (up to 105.6 × 106 g molV-1 h-1) and high copolymerization ability toward ethylene/norbornene copolymerization. By adjusting the polymerization conditions, copolymers with norbornene insertion ratios of 8.1%-30.9% can be obtained. Complex V7 was further studied for ethylene/1-hexene copolymerization, and the obtained copolymer displayed a moderate 1-hexene insertion ratio of 1.2%. Complex V7 displayed high activity and high copolymerization ability while having thermal stability. The results showed that 8-anilide-5,6,7-trihydroquinoline ligands with fused rigid-flexible rings were beneficial for vanadium catalysts.

Application and synthesis of thiazole ring in clinically approved drugs.

The development of heterocyclic derivatives has progressed considerably over the past few decades, and many new agents of synthetic and natural origin have been produced. Among heterocyclic compounds, thiazole is a unique five-membered heterocyclic motif characterized by nitrogen and sulfur atoms, which is widely used as an important core skeleton in a variety of pharmaceutically important compounds due to their diverse biological activities, such as antibacterial, antivirus, and antifungal. To the best of our knowledge, more than 90 thiazole-containing derivatives have been currently under clinical investigation, and some thiazole analogs have been approved to treat various diseases. As the potentially privileged scaffolds, thiazole derivatives can be further extensively explored to search for new drugs characterized by improved therapeutic efficacy and similar biological targets. This review aims to outline the applications and synthetic routes of some representative thiazole-containing drugs approved in the clinic, which may guide medicinal researchers to rationally design more effective thiazole-containing drug candidates.

Chemical analysis of selected harmful and potentially harmful constituents and in vitro toxicological evaluation of leading flavoured e-cigarette aerosols in the Chinese market.

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.

Renewable Vanillin-Based Thermoplastic Polybutadiene Rubber: High Strength, Recyclability, Self-Welding, Shape Memory, and Antibacterial Properties.

The vast majority of traditional vulcanized rubber products are insoluble and infusible, which is difficult to reprocess and biodegrade, resulting in black pollution. In addition, although most rubber materials based on covalent adaptive networks (CANs) can achieve structural reconstruction, the lack of traditional vulcanization system leads to a decline in strength. In this study, biobased vanillin derivatives (PV) were synthesized to cross-link the commercially available 1,2-polybutadiene rubber precursor to construct imine-based CANs, thereby fabricating a resource-renewable, recyclable, and degradable high-performance rubber material. Due to the rigid tripod structure of the PV, the tensile strength of the material can achieve as high as 16.24 MPa, ranking among the best in the field of recyclable polybutadiene-based materials. Benefiting from the dynamic imine unit, the "dynamic covalent bridge" can be re-established to repair the damaged network and endow the material with excellent weldability. And, shape memory faculty of the material was proved and depicted. Moreover, this material displayed excellent antibacterial property originates from the introduced Schiff-base structure. By mixing with graphene, the application of action sensors can also be achieved.

Critical hydraulic gradient and fine particle migration of sand under upward seepage flow.

In order to study the mechanism of seepage-induced geotechnical damage and characteristics of fine particle migration in sandy soil, a one-dimensional upward seepage test device was used and a series of upward seepage flow tests of sand were conducted. In these experiments, the permeability, fine particle migration and redistribution under different hydraulic gradients were investigated. The results show that local hydraulic gradient in the sand sample is larger than the critical hydraulic gradient calculated by the Terzaghi's Equation. The seepage force will induce the fine soil particles to migrate along water flow direction and then cause the redistribution and reconsolidation of sand particles. Under the test condition, fine particles (< 0.075 mm) and fine sand particles (0.075-0.25 mm) dominate in the lost soil particles. Soil particles larger than 0.6 mm are hardly to lose.

Self-Strengthening, Self-Welding, Shape Memory, and Recyclable Polybutadiene-Based Material Driven by Dual-Dynamic Units.

A covalent adaptable network can endow rubber materials with recyclability and reprocessability and is expected to alleviate black pollution caused by end-of-life rubber. However, the loss of traditional vulcanization systems severely sacrifices their strength, and the tensile strength in the current study rarely exceeds 10 MPa unless fillers are added. In this work, we proposed a self-strengthening process based on dual-dynamic units (imine and disulfide), briefly, under heating, phenylsulfur radicals generated from aromatic disulfide bonds can react with double bonds (mostly vinyl) and/or couple with allyl sites, thus reforming a stronger cross-linked network. The neighboring imine unit is not affected and provides excellent thermal reprocessability and chemical recyclability. The result shows that the tensile strength can reach 19.27 MPa via self-strengthening without adding fillers or any other additives, and this ultra-high-strength is much higher than those of all known recyclable polybutadiene-based rubber materials. In addition, the material also has malleability, shape memory, and self-welding properties. By doping carbon nanotubes, a recyclable conductive composite can also be achieved. In general, we envision that this enhanced strategy has great potential to be generalized for all elastomers containing double bonds (such as styrene-butadiene rubber, nitrile rubber, isoprene rubber, and their derivatives). The reprocessability and self-welding are practical for on-site assembly or repair of composite parts and extend the service life of materials.