The specific crystalline form of a compound remarkably affects its physicochemical properties.Therefore,a detailed analysis of the structural features and intermolecular interactions of a multi-component crystal is fe...The specific crystalline form of a compound remarkably affects its physicochemical properties.Therefore,a detailed analysis of the structural features and intermolecular interactions of a multi-component crystal is feasible to understand the relationships among the structure,physicochemical properties and the formation mechanism.In the present study,three novel cocrystal salt solvates of rhein and berberine were reported for the first time.Various solid characterizations and theoretical computations based on density functional theory(DFT)were carried out to demonstrate the intermolecular interactions.The theoretical computation shows that the strongest interaction existed between berberine cation and rhein anion,and the electrostatic interaction play a dominant role.However,no salt bond was observed between them.Further intrinsic dissolution rate analysis in water shows that the monohydrate exhibits 17 times enhancement in comparison with rhein.The rhein and berberine combined in ionic state in cocrystal salt is the main reason for the solubility improvement.This paper suggests that the interactions between the different components can be visualized and qualitatively and quantitatively analyzed by theoretical computation,which is helpful to understand the relationship between stereochemical structure and physicochemical properties of multi-component complex.展开更多
Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are reg...Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity.In this work,we experimentally characterized the form II anhydrous theophylline(THPa)and its monohydrate(THPm)for their distinct plastic and elastic behaviors.Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing.We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa,and possibly other simple aromatic compounds.Meanwhile,water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity.Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.展开更多
Inspired by tug-of-war,a game-changing bone-tendon fixation paradigm was developed.Specifically,injectable citrate-based bioactive self-expansive and planar-fixing screw(iCSP-Scr)consisting of reactive isocyanate(NCO)...Inspired by tug-of-war,a game-changing bone-tendon fixation paradigm was developed.Specifically,injectable citrate-based bioactive self-expansive and planar-fixing screw(iCSP-Scr)consisting of reactive isocyanate(NCO)terminalized citrate-based polyurethane,proanthocyanidin modified hydroxyapatite(HAp)and water(with/without porogen)was developed and administrated in the bone-tendon gap.Instead of the“point to point”tendon fixation by traditional interface screws,along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap,the tendon graft was evenly squeezed into the bone tunnel in a“surface to surface”manner to realize strong and stable bone-tendon fixation via physical expansion,mechanical interlocking and chemical bonding(between–NCO and the–NH2,–SH groups on bone matrix).The optimized iCSP-Scr exhibited rapid crosslinking,moderate expansion rate,high porosity after crosslinking,as well as tunable elasticity and toughness.The iCSP-Scr possessed favorable biodegradability,biocompatibility,and osteoinductivity derived from citrate,PC and HAp,it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock,ultimately leading to stronger tendon fixation(pull-out force 106.15±23.15 N)comparing to titanium screws(93.76±17.89 N)after 14 weeks’ACL reconstruction in a rabbit model.The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing,but also can be expanded into other osteogenic application scenarios.展开更多
Three polymorphs(forms I,II and V)of isonicotinamide(INA)were mechanically flexible and exhibited one-dimensional(1 D)plasticity.Anisotropic intermolecular interactions contribute to the plasticity of single crystals:...Three polymorphs(forms I,II and V)of isonicotinamide(INA)were mechanically flexible and exhibited one-dimensional(1 D)plasticity.Anisotropic intermolecular interactions contribute to the plasticity of single crystals:weak dispersive interactions between slip planes such as 1 D columns in forms I and II or 2 D layers in form V were stabilized by strong hydrogen bonds,allowing the layer or column's surface to glide smoothly without hindrance.The disparity of intermolecular interactions on plastic properties of INA polymorphic crystals was confirmed by energy framework analysis,nanoindentation tests and micro-Raman spectroscopy.The crystal which exhibits plastic property provides a promising application in pharmaceuticals and material sciences.展开更多
Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood...Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood.Here,we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey(NHANES).Additionally,we investigated TCS’s influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS(0.361–48.2μg/L)for 21 days.Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests.Transcriptomics,proteomics analyses,and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption.Significant correlations were found between TCS exposure and estradiol,testosterone,and sex hormone-binding globulin levels in NHANES participants.In addition,TCS exposure inhibited ovary development and spermatogenesis in zebrafish.Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity.Moreover,TCS exposure induced nervous system impairment,as evidenced by histological changes and altered motor behavior,possibly associated with oxidative damage.Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure.Overall,this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.展开更多
Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis,including erythema,scales,or scaly plaques on the skin.These symptoms significantly affect patients...Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis,including erythema,scales,or scaly plaques on the skin.These symptoms significantly affect patients'quality of life and cause severe physical and psychological distress.However,current treatment strategies have limited therapeutic effect and may lead to adverse side effects.In this study,we present the novel organic photosensitizer TBTDC[5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile]nanoparticles(NPs)with aggregation-induced emission(AIE)characteristics to mediate photodynamic therapy(TBTDC NP-PDT)for psoriasis treatment.We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes.Furthermore,TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress(ERS)-mediated autophagy,which can also enhance apoptosis.Importantly,TBTDC NPs show no cytotoxicity toward keratinocytes.These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo.Overall,our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.展开更多
The revolutionary role of tissue adhesives in wound closure,tissue sealing,and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing.In contrast to the us...The revolutionary role of tissue adhesives in wound closure,tissue sealing,and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing.In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators(exemplified by sodium periodate and silver nitrate),herein,the natural polyphenolic compound tannic acid(TA)was used to achieve near instantaneous(<25s),hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant,anti-inflammatory,and antimicrobial activities(3A-TCMBAs).The resulting materials were self-healing and possessed low swelling ratios(<60%)as well as considerable mechanical strength(up to~1.0 MPa),elasticity(elongation~2700%),and adhesion(up to 40 kPa).The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability,favorable cytocompatibility and cell migration,as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli(>90%bacterial death upon near-infrared(NIR)irradiation).In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs+NIR treatment could promote wound closure and collagen deposition and improve the collagen Ⅰ/Ⅲ ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines.Further,phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation&remodeling of the extracellular matrix(ECM)in the late stage(supported by phased CD31(platelet endothelial cell adhesion molecule-1)PDGF(platelet-derived growth factor)and VEGF(vascular endothelial growth factor)expression as well as elevated matrix metalloprotein-9(MMP-9)expression on day 21),resulting in scarless wound healing.The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant,new class of bioadhesive.展开更多
基金the Drug Innovation Major Project(No.2018ZX09711001-001-015)the CAMS Innovation Fund for Medical Sciences(No.2020-I2M-1-003)。
文摘The specific crystalline form of a compound remarkably affects its physicochemical properties.Therefore,a detailed analysis of the structural features and intermolecular interactions of a multi-component crystal is feasible to understand the relationships among the structure,physicochemical properties and the formation mechanism.In the present study,three novel cocrystal salt solvates of rhein and berberine were reported for the first time.Various solid characterizations and theoretical computations based on density functional theory(DFT)were carried out to demonstrate the intermolecular interactions.The theoretical computation shows that the strongest interaction existed between berberine cation and rhein anion,and the electrostatic interaction play a dominant role.However,no salt bond was observed between them.Further intrinsic dissolution rate analysis in water shows that the monohydrate exhibits 17 times enhancement in comparison with rhein.The rhein and berberine combined in ionic state in cocrystal salt is the main reason for the solubility improvement.This paper suggests that the interactions between the different components can be visualized and qualitatively and quantitatively analyzed by theoretical computation,which is helpful to understand the relationship between stereochemical structure and physicochemical properties of multi-component complex.
基金supported by the Young Scientists Promotion Fund of Natural Science Foundation of Guangdong Province,National Natural Science Foundation of China(No.81703438)the Key R&D Program of Shandong Province(No.2021ZDSYS26)National Science and Technology Major Project of China(No.2018ZX09711001-001-013)+1 种基金CAMS Innovation Fund for Medical Sciences(No.2017-I2M-3-010)Student Innovation Training Program(No.201812121093)。
文摘Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity.In this work,we experimentally characterized the form II anhydrous theophylline(THPa)and its monohydrate(THPm)for their distinct plastic and elastic behaviors.Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing.We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa,and possibly other simple aromatic compounds.Meanwhile,water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity.Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.
基金Youth Talent of Guangdong Special Support Program(0620220207)Natural Science Foundation of China(Grant Nos.U21A2099,82272453,and 82102545)+2 种基金China Postdoctoral Science Foundation(Grant No.2022M721515)Basic and Applied Basic Research Project of Guangzhou City(202201011774)Open Program from Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Disease.
文摘Inspired by tug-of-war,a game-changing bone-tendon fixation paradigm was developed.Specifically,injectable citrate-based bioactive self-expansive and planar-fixing screw(iCSP-Scr)consisting of reactive isocyanate(NCO)terminalized citrate-based polyurethane,proanthocyanidin modified hydroxyapatite(HAp)and water(with/without porogen)was developed and administrated in the bone-tendon gap.Instead of the“point to point”tendon fixation by traditional interface screws,along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap,the tendon graft was evenly squeezed into the bone tunnel in a“surface to surface”manner to realize strong and stable bone-tendon fixation via physical expansion,mechanical interlocking and chemical bonding(between–NCO and the–NH2,–SH groups on bone matrix).The optimized iCSP-Scr exhibited rapid crosslinking,moderate expansion rate,high porosity after crosslinking,as well as tunable elasticity and toughness.The iCSP-Scr possessed favorable biodegradability,biocompatibility,and osteoinductivity derived from citrate,PC and HAp,it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock,ultimately leading to stronger tendon fixation(pull-out force 106.15±23.15 N)comparing to titanium screws(93.76±17.89 N)after 14 weeks’ACL reconstruction in a rabbit model.The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing,but also can be expanded into other osteogenic application scenarios.
基金sponsored by National Key R&D Program of China(No.2016YFC1000900)National Science and Technology Major Project of China(No.2018ZX09711001-001-013)National Natural Science Foundation of China(No.81703438)。
文摘Three polymorphs(forms I,II and V)of isonicotinamide(INA)were mechanically flexible and exhibited one-dimensional(1 D)plasticity.Anisotropic intermolecular interactions contribute to the plasticity of single crystals:weak dispersive interactions between slip planes such as 1 D columns in forms I and II or 2 D layers in form V were stabilized by strong hydrogen bonds,allowing the layer or column's surface to glide smoothly without hindrance.The disparity of intermolecular interactions on plastic properties of INA polymorphic crystals was confirmed by energy framework analysis,nanoindentation tests and micro-Raman spectroscopy.The crystal which exhibits plastic property provides a promising application in pharmaceuticals and material sciences.
基金Science and Technology Project of Guangdong Province,China(2022A0505050035)National Natural Science Foundation of China(82273656,82304177,82073519)+5 种基金Guangdong Basic Applied Basic Research Foundation(2022A1515010610,Guangdong-Dongguan Joint grant 2022A1515111098,Guangdong-Guangzhou Joint grant 2023A1515110373)Chinese Postdoctoral Science Foundation(2023M741553,2022M721486,2023T160295)Postdoctoral Fellowship Program of CPSF(GZC20231055)National Training Program of Innovation and Entrepreneurship for Undergraduates(202212121034,S202312121124)Guangdong Provincial Key Laboratory of Tropical Disease Research(2017B030314035)NMPA Key Laboratory for Safety Evaluation of Cosmetics,and the GDMPA Project of Scientific and Technological Innovation(2024ZDZ09).
文摘Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood.Here,we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey(NHANES).Additionally,we investigated TCS’s influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS(0.361–48.2μg/L)for 21 days.Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests.Transcriptomics,proteomics analyses,and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption.Significant correlations were found between TCS exposure and estradiol,testosterone,and sex hormone-binding globulin levels in NHANES participants.In addition,TCS exposure inhibited ovary development and spermatogenesis in zebrafish.Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity.Moreover,TCS exposure induced nervous system impairment,as evidenced by histological changes and altered motor behavior,possibly associated with oxidative damage.Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure.Overall,this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.
基金supported by the Natural Science Funding of Guangdong Province(2022A1515012312 and 2021A1515010023)the National Natural Science Funding of China(82070083)Dongguan Social development technology projects Science and Technology Planning Project(20231800940792).
文摘Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis,including erythema,scales,or scaly plaques on the skin.These symptoms significantly affect patients'quality of life and cause severe physical and psychological distress.However,current treatment strategies have limited therapeutic effect and may lead to adverse side effects.In this study,we present the novel organic photosensitizer TBTDC[5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile]nanoparticles(NPs)with aggregation-induced emission(AIE)characteristics to mediate photodynamic therapy(TBTDC NP-PDT)for psoriasis treatment.We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes.Furthermore,TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress(ERS)-mediated autophagy,which can also enhance apoptosis.Importantly,TBTDC NPs show no cytotoxicity toward keratinocytes.These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo.Overall,our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.
基金funded by the National Natural Science Foundation of China(NSFC,Grant No.U21A2099,82102545)the Chinese Postdoctoral Science Foundation(Grant No.2021M701627)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2022A1515011982,2020A1515110062).
文摘The revolutionary role of tissue adhesives in wound closure,tissue sealing,and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing.In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators(exemplified by sodium periodate and silver nitrate),herein,the natural polyphenolic compound tannic acid(TA)was used to achieve near instantaneous(<25s),hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant,anti-inflammatory,and antimicrobial activities(3A-TCMBAs).The resulting materials were self-healing and possessed low swelling ratios(<60%)as well as considerable mechanical strength(up to~1.0 MPa),elasticity(elongation~2700%),and adhesion(up to 40 kPa).The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability,favorable cytocompatibility and cell migration,as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli(>90%bacterial death upon near-infrared(NIR)irradiation).In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs+NIR treatment could promote wound closure and collagen deposition and improve the collagen Ⅰ/Ⅲ ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines.Further,phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation&remodeling of the extracellular matrix(ECM)in the late stage(supported by phased CD31(platelet endothelial cell adhesion molecule-1)PDGF(platelet-derived growth factor)and VEGF(vascular endothelial growth factor)expression as well as elevated matrix metalloprotein-9(MMP-9)expression on day 21),resulting in scarless wound healing.The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant,new class of bioadhesive.
