Synergistic effects of low-dose arsenic and N-methyl-N'-nitro-N-nitrosoguanidine co-exposure by altering gut microbiota and intestinal metabolic profile in rats.

Biological organisms are exposed to low-dose arsenic or N-nitro compounds (NOCs) alone or in combination worldwide, especially in areas with high cancer prevalence through drinking water or food exposure; however, information on their combined exposure effects is limited. Here, we conducted an in-depth study of the effects on the gut microbiota, metabolomics, and signaling pathways using rat models exposed to arsenic or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), one of the most active carcinogenic NOCs, separately or in combination with metabolomics and high-throughput sequencing. Compared to exposure alone, combined exposure to arsenic and MNNG exacerbated damage to gastric tissue morphology, interfered with intestinal microflora and substance metabolism, and exerted a stronger carcinogenic effect. This may be related to intestinal microbiota disorders, including Dyella, Oscillibacter, Myroides, and metabolic pathways such as glycine, serine, and threonine metabolism, arginine biosynthesis, central carbon metabolism in cancer, and purine and pyrimidine metabolism, thereby enhancing the cancer-causing effects of gonadotrophin-releasing hormone (GnRH), P53, and Wnt signaling pathways.

Two birds one stone: ß-fluoropyrrolyl-cysteine SNAr chemistry enabling functional porphyrin bioconjugation.

Bioconjugation, a synthetic tool that endows small molecules with biocompatibility and target specificity through covalent attachment of a biomolecule, holds promise for next-generation diagnosis or therapy. Besides the establishment of chemical bonding, such chemical modification concurrently allows alteration of the physicochemical properties of small molecules, but this has been paid less attention in designing novel bioconjugates. Here, we report a "two birds one stone" methodology for irreversible porphyrin bioconjugation based on ß-fluoropyrrolyl-cysteine SNAr chemistry, in which the ß-fluorine of porphyrin is selectively replaced by a cysteine in either peptides or proteins to generate novel ß-peptidyl/proteic porphyrins. Notably, due to the distinct electronic nature between fluorine and sulfur, such replacement makes the Q band red-shift to the near-infrared region (NIR, >700 nm). This facilitates intersystem crossing (ISC) to enhance the triplet population and thus singlet oxygen production. This new methodology features water tolerance, a fast reaction time (15 min), good chemo-selectivity, and broad substrate scope, including various peptides and proteins under mild conditions. To demonstrate its potential, we applied porphyrin ß-bioconjugates in several scenarios, including (1) cytosolic delivery of functional proteins, (2) metabolic glycan labeling, (3) caspase-3 detection, and (4) tumor-targeting phototheranostics.

A multi-module soft robotic arm with soft actuator for minimally invasive surgery.

BACKGROUND: Compared to traditional rigid robotic arms, soft robotic arms are flexible, environmentally adaptable and biocompatible. Recently, most minimally invasive cardiac procedures still rely on traditional rigid surgical tools. However, rigid tools lack sufficient bending angles, which are high-risk in terms of contact with tissues and organs. METHODS: A soft robotic arm with multiple degrees of freedom was designed to repair atrial septal defects in cardiac surgery. The developed multi-module soft robotic arm consists of four different units, including a bending unit, a turning unit, a stretching unit and gripper units. The three movement units can reach the specified position, and the gripper units can hold a surgical tool stably, such as a suture needle in cardiac surgery. RESULTS: A cardiac surgery to repair an atrial septal defect has been completed, validating the reliability and functionality of the developed multi-module soft robotic arm. CONCLUSIONS: The multi-module flexible soft robotic arm for minimally invasive surgery proposed in this paper can reach the designated surgical area during surgery to repair Atrial Septal Defects. Meanwhile, the design of the actuator of the robot arm was used a completely soft silicone material replacing the rigid material, which releases the contact trauma of the organs during the surgery.

Double-Layer MWCNTs@HPPS Photothermal Paper for Water Purification with Strong Acid-Alkali Corrosion Resistance.

Solar-driven interfacial evaporation technology has been identified as a promising method to relieve the global water crisis, and it is particularly important to design an ideal structure of the solar thermal conversion evaporation device. In this paper, hydrophilic polyphenylene sulfide (HPPS) paper with loose structure and appropriate water transmission performance was designed as the based-material, and multi-walled carbon nanotubes (MWCNTs) layer with excellent photothermal conversion performance was constructed to realize the high-efficiency solar-driven evaporation. Under tail swabbing mode, the cold evaporation surface on the back of the evaporator greatly improved the evaporation rate, cut off the heat transfer channel to bulk water, and achieved the maximum evaporation rate of 1.23 L/m2·h. Ethyl cellulose (EC) was introduced to adjust the water supply performance of HPPS layer, and a large specific surface area of cold evaporation was obtained, thus improving the water evaporation rate. In the simulation experiment of seawater desalination and dye wastewater treatment, it showed good water purification capacity and acid/alkali-resistance, which had great practical application significance.

Epidermal stem cells participate in the repair of scalds via Nanog and Myc regulation.

Epidermal stem cells (EpSCs) with high expression of regulatory factor Nanog can promote wound healing. The aim of the present study was to investigate the effectiveness and mechanism of epidermal stem cells (EpSCs) in healing scalds and the underlying molecular mechanism. Mouse EpSCs were isolated from skin tissues and cultured in vitro. First, the proliferative ability of EpSCs was determined via the upregulation and downregulation of Nanog expression levels in EpSCs using the MTS­assay. Second, a wound healing assay of the EpSCs with different Nanog expression levels was performed to investigate cell migratory capacities. Third, the protein expression levels of various proteins in EpSCs with Nanog overexpression or knockdown, were determined. Finally, the transfected EpSCs were applied to the rat scald model to observe their effect on scald healing. Subsequently, wound scores, re­epithelialization and capillary density were determined histologically. The results demonstrated that Nanog overexpression enhanced the proliferative ability of EpSCs via cellular (c)­Myc. Moreover, the LV­Nanog group of EpSCs with increased Nanog expression levels exhibited improved healing abilities in the wound healing test than control group. Using western blotting, it was demonstrated that EpSCs that were transfected with a Nanog­overexpression vector expressed high Nanog protein expression levels, whereas small interfering RNA­Nanog­transfected EpSCs exhibited low Nanog protein expression levels. Furthermore, c­Myc expression was synchronized with Nanog expression. It was also revealed that as the expression levels of c­Myc increased, p53 expression levels also increased. In the rat scald model, Nanog­overexpressing EpSCs enhanced wound closure and re­epithelialization. The EpSCs with Nanog knockdown exhibited the opposite effects. The present study therefore indicated that Nanog may have a positive effect on scald healing in rats, which supports its use in EpSC­based treatments against scalds. Furthermore, it was suggested that c­Myc potentially serves a key role in this process and that this process avoids cancerization by relying on the supervision of p53.

Bioorthogonal Lanthanide Molecular Probes for Near-Infrared Fluorescence and Mass Spectrometry Imaging.

We report here the development of clickable and highly near-infrared (NIR) fluorescent lanthanide (Ln) complexes for bioorthogonal labeling of biomolecules. These azide- or alkyne-functionalized Ln complexes are hydrophilic and fluorogenic, exhibiting a strong increase of NIR fluorescence upon conjugation with biomolecules. Metabolic labeling of biomolecules with azide or alkyne, followed by click labeling with the Ln complexes, enables NIR fluorescence (NIRF) imaging of DNA, RNA, proteins, and glycans in cells. Furthermore, multicolor imaging is performed by combining click-labeling with the Ln complexes and immunostaining. In addition, the Ln complexes is compatible with click-expansion microscopy (click-ExM), which enables high-resolution NIRF imaging of cellular glycoproteins. Finally, the Ln complexes can be used for time-of-flight secondary-ion mass spectrometry (ToF-SIMS) imaging, thus achieving the first example of dual-modal imaging combining NIRF and SIMS microscopies.

Lanthanide porphyrinoids as molecular theranostics.

In recent years, lanthanide (Ln) porphyrinoids have received increasing attention as theranostics. Broadly speaking, the term 'theranostics' refers to agents designed to allow both disease diagnosis and therapeutic intervention. This Review summarises the history and the 'state-of-the-art' development of Ln porphyrinoids as theranostic agents. The emphasis is on the progress made within the past decade. Applications of Ln porphyrinoids in near-infrared (NIR, 650-1700 nm) fluorescence imaging (FL), magnetic resonance imaging (MRI), radiotherapy, and chemotherapy will be discussed. The use of Ln porphyrinoids as photo-activated agents ('phototheranostics') will also be highlighted in the context of three promising strategies for regulation of porphyrinic triplet energy dissipation pathways, namely: regioisomeric effects, metal regulation, and the use of expanded porphyrinoids. The goal of this Review is to showcase some of the ongoing efforts being made to optimise Ln porphyrinoids as theranostics and as phototheranostics, in order to provide a platform for understanding likely future developments in the area, including those associated with structure-based innovations, functional improvements, and emerging biological activation strategies.

Luminescent Metal Complexes for Bioassays in the Near-Infrared (NIR) Region.

Near-infrared (NIR, 700-1700 nm) luminescent imaging is an emerging bioimaging technology with low photon scattering, minimal autofluorescence, deep tissue penetration, and high spatiotemporal resolution that has shown fascinating promise for NIR imaging-guided theranostics. In recent progress, NIR luminescent metal complexes have attracted substantially increased research attention owing to their intrinsic merits, including small size, anti-photobleaching, long lifetime, and metal-centered NIR emission. In the past decade, scientists have contributed to the advancement of NIR metal complexes involving efforts to improve photophysical properties, biocompatibility, specificity, pharmacokinetics, in vivo visualization, and attempts to exploit new ligand platforms. Herein, we summarize recent progress and provide future perspectives for NIR metal complexes, including d-block transition metals and f-block lanthanides (Ln) as NIR optical molecular probes for bioassays.

Gadolinium(III) Porphyrinoid Phototheranostics.

Molecular phototheranostics as an emerging field of modern precision medicine has recently attracted increasing research attention owing to non-invasiveness, high precision, and controllable nature of light. In this work, we reported promising gadolinium (Gd3+ ) porphyrinoids as phototheranostic agents for magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The synthesized Gd-1-4-Glu featured with meso-glycosylation and ß-lactonization to endow good biocompatibility and improved photophysical properties. In particular, ß-lactonization of glycosylated Gd3+ porphyrinoids substantially red-shifted Q band absorption to near-infrared (NIR) region and boosted generation of reactive oxygen species including 1 O2 , and some radical species that engaged in both type II and type I PDT pathways. In addition, the number and regioisomerism of ß-oxazolone moieties was observed to play an essential role in improving longitude relaxivity (r1 ) of Gd-1-4-Glu of up to 4.3±0.2 mM-1 s-1 by affecting environmental water exchange. Taking Gd-4-Glu as a promising complex, we further achieved real-time T1 -weighted MRI and PDT on HeLa tumour mice in vivo, revealing the appealing potential of Gd3+ porphyrinoids in phototheranostics.

Recent progress in metal-based molecular probes for optical bioimaging and biosensing.

Biological imaging and biosensing from subcellular/cellular level to whole body have enabled non-invasive visualisation of molecular events during various biological and pathological processes, giving great contributions to the rapid and impressive advances in chemical biology, drug discovery, disease diagnosis and prognosis. Optical imaging features a series of merits, including convenience, high resolution, good sensitivity, low cost and the absence of ionizing radiation. Among different luminescent probes, metal-based molecules offer unique promise in optical bioimaging and biosensing in vitro and in vivo, arising from their small sizes, strong luminescence, large Stokes shifts, long lifetimes, high photostability and tunable toxicity. In this review, we aim to highlight the design of metal-based molecular probes from the standpoint of synthetic chemistry in the last 2 years for optical imaging, covering d-block transition metal and lanthanide complexes and multimodal imaging agents.

Celecoxib reverses the glioblastoma chemo-resistance to temozolomide through mitochondrial metabolism.

Temozolomide (TMZ) is used for the treatment of high-grade gliomas. Acquired chemoresistance is a serious limitation to the therapy with more than 90% of recurrent gliomas showing little response to a second line of chemotherapy. Therefore, it is necessary to explore an alternative strategy to enhance the sensitivity of glioblastoma (GBM) to TMZ in neuro-oncology. Celecoxib is well known and widely used in anti-inflammatory and analgesic. Cyclooxygenase-2 (COX-2) expression has been linked to the prognosis, angiogenesis, and radiation sensitivity of many malignancies such as primitive neuroectodermal tumor and advanced melanoma. The objective of this study was to explore the chemotherapy-sensitizing effect of celecoxib on TMZ in GBM cells and its potential mechanisms. From the study, we found that the combination therapy (TMZ 250uM+celecoxib 30uM) showed excellent inhibitory effect to the GBM, the LN229 and LN18, which were the TMZ resistant GBM cell lines. Our data suggest that the combination therapy may inhibits cell proliferation, increases apoptosis, and increases the autophagy on LN229 and LN18. The potential molecular mechanisms were related to mitochondrial metabolism and respiratory chain inhibition.

Electric-Field-Induced Gradient Ionogels for Highly Sensitive, Broad-Range-Response, and Freeze/Heat-Resistant Ionic Fingers.

Human fingers exhibit both high sensitivity and wide tactile range. The finger skin structures are designed to display gradient microstructures and compressibility. Inspired by the gradient mechanical Young's modulus distribution, an electric-field-induced cationic crosslinker migration strategy is demonstrated to prepare gradient ionogels. Due to the gradient of the crosslinkers, the ionogels exhibit more than four orders of magnitude difference between the anode and the cathode side, enabling gradient ionogel-based flexible iontronic sensors having high-sensitivity and broader-range detection (from 3 × 102 to 2.5 × 106  Pa) simultaneously. Moreover, owing to the remarkable properties of the gradient ionogels, the flexible iontronic sensors also show good long-time stability (even after 10 000 cycles loadings) and excellent performance over a wide temperature range (from -108 to 300 °C). The flexible iontronic sensors are further integrated on soft grips, exhibiting remarkable performance under various conditions. These attractive features demonstrate that gradient ionogels will be promising candidates for smart sensor applications in complex and extreme conditions.

Photoinduced Free Radical Promoted Cationic RAFT Polymerization toward "Living" 3D Printing.

Three-dimensional (3D) printing utilizing controlled polymerization systems is emerging as a powerful approach to fabricate "living" objects, which can be further modified with various functionalities. Here, we report photoinduced free radical-promoted cationic reversible addition-fragmentation chain transfer (RAFT) polymerization under broad wavelengths from ultraviolet (UV) to near-infrared (NIR) light. A commercially available iron catalyst, cyclopentadienyl iron dicarbonyl dimer (Fe2(Cp)2(CO)4), was used as the photocatalyst, and several diphenyliodonium salts were examined as oxidants. Various poly(vinyl ether)s with controlled molecular weights and a narrow dispersity (1.06-1.32) were prepared through this method. Relatively high chain-end fidelity can be observed and has been demonstrated by successful chain-extension experiments. In addition, benefiting from the penetrating ability of NIR light, 3D objects with different thicknesses were achieved by employing stereolithography-based 3D printing techniques. Furthermore, the postfunctionalization of these 3D printed objects with fluorescent monomers provides a facile method to build 3D objects with complex functionality and potential applications in anticounterfeiting materials.

Porpholactone Chemistry: Shining New Light on an Old Cofactor.

The emergence of porpholactone chemistry, discovered over 30 years ago, has significantly stimulated the development of biomimetic tetrapyrrole chemistry. It offers an opportunity, through modifications of non-pyrrolic building blocks, to clarify the relationship between chemical structure and excited-state properties, deciphering the structural code for the biological functions of life pigments. With intriguing photophysical properties in the red to near-infrared (NIR) regions, facile modulation of their electronic nature by fine-tuning chemical structures, and coordination ability with diverse metal ions, these novel porphyrinoids have favorable prospects in the fields of optical materials, bioimaging and therapy, and catalysis. In this Minireview, we summarize the brief history of porpholactone chemistry, and focus on the studies carried out in our group, particularly on the regioisomeric effect, NIR lanthanide luminescence, and metal catalysis. We outline the perspectives of these compounds in the construction of porpholactone-related biomedical applications and optical and energy materials, in order to inspire more interest and further advance bioinspired inorganic chemistry and lanthanide chemical biology.

Porpholactone Chemistry: Shining New Light on an Old Cofactor.

Invited for this month's cover is the group of Jun-Long Zhang, Peking University, Beijing. The cover picture shows the porpholactone cofactor, which play unique roles in molecular imaging and therapy (or theranostics), catalysis, as well as energy and optical materials. This class of molecules is ideal for more intriguing scientific research and future practical applications. Read the full text of the Minireview at 10.1002/cplu.202000494.

Efficient synthesis of 2-aryl-2H-indazoles by base-catalyzed benzyl C-H deprotonation and cyclization.

A straightforward and efficient method for the preparation of 2-aryl-2H-indazoles from ortho-alkyl substituted azoxybenzenes is presented. The reaction proceeds through base-catalyzed benzyl C-H deprotonation and cyclization to afford 2-aryl-2H-indazoles in good yields. This synthetic strategy can be applied to the construction of several fluorescent and bioactive molecules.

Integrated systematic approach increase greenhouse tomato yield and reduce environmental losses.

High input - high output greenhouse vegetable systems are responsible for nutrient surpluses and environmental losses. Integrated strategies that improve soil, crop and nutrient management are needed to ensure more sustainable production systems. We conducted a two-year field experiment to evaluate the potential of integrated soil-crop system management (ISSM) practices to improve the productivity and environmental outcomes from an intensive greenhouse tomato production system in the Yangtze River Basin, China. Four treatments were tested: i) farmers' practice (FP); ii) soil remediation (SR), where lime nitrogen with compost addition was the only management strategy; iii) a treatment that combined soil remediation with optimized crop planting density (SRCO), which increased planting density for improving crop yield; and iv) integrated soil-crop system management (ISSM), as a systematic integrated approach, which included the combined optimization of soil remediation, crop optimization, and nutrient management. In the integrated soil-crop system management treatment, nutrient management was optimized through adoption of the most appropriate type (formula) of fertilizer for the crop, rate and application timing of synthetic fertilizer, and by substituting poultry manure with compost. Our results indicated that the fruit yield of the integrated soil-crop system management treatment was 104 t ha-1, 13.4%-37.3% higher than that of the other three treatments. The mean reactive nitrogen loss (81.1 kg N ha-1) and the greenhouse gas emissions (6495 kg CO2-eq ha-1) in the farmers' practice treatment were much higher than in the other three treatments (reactive nitrogen loss: 47.9-54.3 kg N ha-1; and greenhouse gas emissions: 4926-5468 kg CO2-eq ha-1, respectively). The mean nitrogen and carbon footprints of the integrated soil-crop system management treatment were significantly lower than those of other treatments, as a result of both the lower fertilizer nitrogen use and the greater yield. This study indicates that integrated soil-crop system management could produce greater yields and increase net profit with reduced nitrogen inputs, whilst reducing the environmental cost associated with conventional farmers' practice in plastic-greenhouse vegetable production systems.

Joint influence of genetic origin and climate on the growth of Masson pine (Pinus massoniana Lamb.) in China.

Adaptive of trees and its correlation with the climatic are causing changes in tree species performance and distribution, which will change breeding programs and influence forest productivity. To further evaluate the joint influence of climatic factors and provenance on the ring width (RW) and ring density (RD) of Masson pine. We selected 18 provenances at Chun'an (CA) and Taizi Mountain (TZS) test site, which representing four different breeding regions, including the south, west, north and east-central regions. The results showed that the provenance effects were significantly for the RW and RD. The provenances from high temperature and low latitude regions had greater mean RW compared to species from local and cold sources. The geographical genetic variation in wood traits is generally weak. The correlation between RW of Masson pine and precipitation was stronger in the relatively arid TZS site compared with that in relatively wet CA site, as well as the effect of temperature and precipitation on RD was earlier than that in CA test site. The response relationship between establishing the width of tree rings and the environmental variables of provenance indicated that during the transition from the northern and western breeding regions to the eastern and southern breeding regions, the response of RW to climate factors changed from being temperature-based to being precipitation-based. In addition, the response of provenance to the climate of seed sources origin showed their own variation characteristics in each breeding area. Therefore, genetic improvement of big diameter wood and wood density can be gain through selection of provenance and analysis of adaptability.

Near-Infrared, Light-Induced Cationic and Radical RAFT Polymerization Catalyzed by Iron Complex.

A near-infrared (NIR) light induced controlled cationic polymerization is presented here. The halide abstraction reaction between the cyclopentadienyl iron dicarbonyl dimer (Fe2(Cp)2(CO)4) and an organic halide is utilized to generate initial radicals or cations under mild conditions, which can be further combined with both radical and cationic reversible addition-fragmentation chain transfer (RAFT) polymerization. Well-defined poly(vinyl ether)s and polyacrylates are prepared successfully under NIR light by this method. The excellent penetration ability of NIR light through thick barriers has been verified by polymerization in the presence of an A4 paper. In addition, iron-based radical polymerization has been used for three-dimensional (3D) printing to fabricate materials with different thicknesses.

Synthesis of selenated isochromenones by AgNO3-catalyzed three-component reaction of alkynylaryl esters, selenium powder and ArB(OH)2.

Reported is the AgNO3-catalyzed three-component reaction of alkynylaryl esters, selenium powder and ArB(OH)2, providing a facile entry to selenated isochromenones. This work highlights the use of selenium powder as a selenium reagent in the synthesis of selenated isochromenones for the first time.