BACKGROUND Odontogenic maxillary sinusitis,often triggered by dental issues like periapical periodontitis,significantly contributes to chronic sinusitis,mainly affecting adults around 50 years old,emphasizing the need...BACKGROUND Odontogenic maxillary sinusitis,often triggered by dental issues like periapical periodontitis,significantly contributes to chronic sinusitis,mainly affecting adults around 50 years old,emphasizing the need for a multidisciplinary diagnostic and treatment approach.AIM To investigate the therapeutic effect and clinical value of root canal therapy combined with nasal endoscopic surgery compared with simple root canal the-rapy in the treatment of severe odontogenic maxillary sinusitis caused by peria-pical periodontitis.METHODS The clinical data,diagnosis,and treatment of 200 patients with severe odonto-genic maxillary sinusitis caused by periapical periodontitis from October 2020 to October 2021 were analyzed retrospectively.Among them,63 patients were treated with simple root canal therapy as the control group,and 137 patients were treated with root canal therapy combined with nasal endoscopic surgery as the observation group.The therapeutic effect,Lund-Kennedy endoscopic score,paranasal sinus Lund-Mackay score,complication rate,recurrence rate,and patient satisfaction were compared between the two groups.RESULTS First,we compared the effective rates:23 cases were cured,22 were improved,and 8 were ineffective in the control group,yielding a total effective rate of 84.90%.Meanwhile,97 cases were cured,34 improved,and 6 were ineffective in the observation group,resulting in a total effective rate of 95.62%.The observation group had a higher total effective rate compared with the control group(P<0.05).Second,we compared the Lund–Kennedy endoscopic score.Before treatment,no significant difference(P>0.05)was observed in this score between the two groups.After treatment,the Lund–Kennedy endoscopic score decreased in both groups.The Lund–Kennedy endoscopic score of the observation group at 3 and 6 mo after treatment was lower compared to that of the control group(P<0.05).Third,we compared the Lund–Mackay score of paranasal sinuses.Before treatment,there was no significant difference in this score between the two groups(P>0.05).After treatment,the Lund–Mackay scores of paranasal sinuses decreased in both groups.The Lund–Mackay scores of paranasal sinuses in the observation group at 3 and 6 mo after treatment were lower compared to those of the control group(P<0.05).Fourth,we compared the incidence and recurrence rate of complications.Three months after treatment,no significant difference was found in the incidence and recurrence rate of complications between the observation group(6.56%)and the control group(9.52%)(P>0.05).However,6 mo after treatment,the incidence and recurrence rate of complications in the observation group(2.91%)was significantly higher compared to that of the control group(12.69%)(P<0.05).Fifth,we compared patient satisfaction.Six months after treatment,the patient satisfaction of the observation group(93.43%)was significantly better than that of the control group(84.12%)(P<0.05).CONCLUSION Root canal therapy combined with nasal endoscopic surgery has a good therapeutic effect on severe odontogenic maxillary sinusitis caused by periapical periodontitis,and it can reduce the injury of maxillary sinus mucosa and bone,and significantly reduce the incidence of complications and recurrence rate.Meanwhile,it has high patient satisfaction and remarkable therapeutic effect,which is suggested to be popularized and applied in clinic.展开更多
Cr coatings,as protective coatings of Zr-alloy fuel claddings,inevitably suffer from irradiation damage before they would possibly run into the accident condition.This study evaluates the radiation and oxidation toler...Cr coatings,as protective coatings of Zr-alloy fuel claddings,inevitably suffer from irradiation damage before they would possibly run into the accident condition.This study evaluates the radiation and oxidation tolerance of three Cr-based coatings with different microstructures(Cr,CrAlSi,and CrAlSiN)through He2+ion irradiation and 1200℃ steam oxidation.The Cr and CrAlSi coatings experienced significant structural degradation,characterized by He bubble aggregation and amplified Kirkendall effects at elevated temperatures.In contrast,the irradiated CrAlSiN coating maintained structural integrity without measurable irradiation hardening.Following annealing at 800℃ for 30 min,approximately 40%of injected He atoms were released,indicating a“self-healing”mechanism.The mechanism is attributed to uniformly distributed,low-density channels that act as sinks and release paths for irradiation-induced defects.Density functional theory simulations suggest that N atoms promote significant rearrangement of ions surrounding the free volume,inhibiting the formation of sites capable of trapping He atoms.Moreover,the CrAlSiN coating exhibited superior oxidation resistance compared to the Cr and CrAlSi coatings,even under high-temperature steam conditions.Notably,the irradiated CrAlSiN sample displayed a significantly thinner oxide scale compared to the pristine one(almost half),owing to a more protective oxide scale and rapid outward diffusion of Cr,Al,and Si through nanochannel veins.These findings illuminate the effects of structure and composition on irradiation and oxidation behavior in Cr-based coatings,offering insights for developing new-generation accident-tolerance fuel coatings for Zr-alloy claddings.展开更多
This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(G...This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(GPA)and 13-hydroxyglucopiericidin A(13-OH-GPA).The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate.Rapid absorption of PA and GPAs in mice was observed,characterized by short half-lives and low bioavailability.Glycosides and hydroxyl groups significantly enhanced the absorption rate(13-OH-GPA>GPA>PA).PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes(CYPs)and uridine diphosphoglucuronosyl transferases(UGTs).Glucuronidation emerged as the primary metabolic pathway,with UGT1A7,UGT1A8,UGT1A9,and UGT1A10 demonstrating high elimination rates(30%-70%)for PA and GPAs.This rapid glucuronidation may contribute to the low bioavailability of GPAs.Despite its low bioavailability(2.69%),13-OH-GPA showed higher kidney distribution(19.8%)compared to PA(10.0%)and GPA(7.3%),suggesting enhanced biological efficacy in kidney diseases.Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability.In conclusion,this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.展开更多
阐述了零部件级释气率程控测试系统的研制思路与方法。以小孔流导法为理论依据,从程控角度出发,将PLC与上位机软件紧密结合,实现了对零部件释气率的全自动测试。该系统可自动生成具有关键信息的测试报告。同时,系统还具备全自动校准工艺...阐述了零部件级释气率程控测试系统的研制思路与方法。以小孔流导法为理论依据,从程控角度出发,将PLC与上位机软件紧密结合,实现了对零部件释气率的全自动测试。该系统可自动生成具有关键信息的测试报告。同时,系统还具备全自动校准工艺,最大程度地保证了测试数据的准确性。控制系统通过PLC自动程序控制真空系统的启停,从而获取真空测试环境;上位机软件与质谱仪(Quadrupole Mass Spectrometer,QMS)进行通讯,采集QMS中的数据,并进行数据分析;上位机软件与PLC程序配合,可保证校准工艺以及测试工艺的自动运行。展开更多
Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.Ho...Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.However,studies on neuroprotective strategies for optic neuropathy have increased in recent years.Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy.Regenerative medicine research into the repair of optic nerve damage using stem cells has Received considerable attention.Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGCfriendly microenvironments through paracrine effects.This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury,raising the controversies and unresolved issues surrounding the future of stem cells.展开更多
Dear Editor,The choice of surgical intervention for nanophthalmos patients with secondary angle-closure glaucoma poses a challenging decision for ophthalmologists.Because nanophthalmos patients who have undergone filt...Dear Editor,The choice of surgical intervention for nanophthalmos patients with secondary angle-closure glaucoma poses a challenging decision for ophthalmologists.Because nanophthalmos patients who have undergone filtration surgery or other intraocular procedures are more susceptible to severe complications,including choroidal effusion,malignant glaucoma,and explosive choroidal hemorrhage,all of which can lead to vision loss[1].This dilemma is particularly pronounced in patients with shorter axial lengths.Micropulse transscleral laser therapy(M-TLT),also known as micropulse transscleral cyclophotocoagulation(MP-TSCPC),is a nonincisional laser therapy surgery for glaucoma[2].In 2015,Golan and Kurtz[3]were the first to report four patients with secondary angle-closure glaucoma in nanophthalmos with axial lengths ranging between 17 and 19 mm(mean 18 mm)who were successfully treated with M-TLT,and choroidal detachment was observed in all patients(recovery spontaneously in two patients and recovery after systemic steroid treatment in the other two),of which two had a slight decrease in visual acuity.展开更多
Correction:Natural Products and Bioprospecting(2024)14:33 https://doi.org/10.1007/s13659-024-00455-x Following publication of the original article[1],the authors reported that the original version of this article unfo...Correction:Natural Products and Bioprospecting(2024)14:33 https://doi.org/10.1007/s13659-024-00455-x Following publication of the original article[1],the authors reported that the original version of this article unfortunately contained mistakes.Page 1,section“Abstract”,the originally published texts were:Despite low bioavailability(0.024%),N-hydap exhibited a higher distribution in the lungs(26.26%),accounting for its efficacy against SCLC.展开更多
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) datas...Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.展开更多
N-Hydroxyapiosporamide(N-hydap),a marine product derived from a sponge-associated fungus,has shown promising inhibitory effects on small cell lung cancer(SCLC).However,there is limited understanding of its metabolic p...N-Hydroxyapiosporamide(N-hydap),a marine product derived from a sponge-associated fungus,has shown promising inhibitory effects on small cell lung cancer(SCLC).However,there is limited understanding of its metabolic pathways and characteristics.This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s(CYPs)and UDP-glucuronosyltransferases(UGTs),as well as human/rat/mice microsomes,and also the pharmacokinetic properties by HPLC-MS/MS.Additionally,the cocktail probe method was used to investigate the potential to create drug-drug interactions(DDIs).N-Hydap was metabolically unstable in various microsomes after 1 h,with about 50%and 70%of it being eliminated by CYPs and UGTs,respectively.UGT1A3 was the main enzyme involved in glucuronidation(over 80%),making glucuronide the primary metabolite.Despite low bioavailability(0.024%),N-hydap exhibited a higher distribution in the lungs(26.26%),accounting for its efficacy against SCLC.Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity.Furthermore,N-hydap was found to affect the catalytic activity of drug metabolic enzymes(DMEs),particularly increasing the activity of UGT1A3,suggesting potential for DDIs.Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy,toxicity,and potential for DDIs.展开更多
CJ Health Technology Co.has been an export-oriented supplier of fitness equipment,boasting leading technology innovation and manufacturing capabilities.However,in the process of expanding into the domestic market,the ...CJ Health Technology Co.has been an export-oriented supplier of fitness equipment,boasting leading technology innovation and manufacturing capabilities.However,in the process of expanding into the domestic market,the challenges of unclear market positioning and lack of brand awareness have emerged as major obstacles.To address these issues,a SWOT analysis was conducted to explore a suitable market positioning strategy for the CJ brand.The analysis reveals that the market demand for commercial fitness equipment is relatively saturated,with fierce competition.In contrast,the home fitness market represents a new blue ocean with promising development opportunities for the CJ brand.Leveraging excellent product quality,stringent quality control measures,and innovation-driven cutting-edge technology,it is recommended that CJ brand fitness equipment target young customers aged between 25 and 35 years old.Additionally,vigorously developing the home fitness product line is proposed to capitalize on this burgeoning market segment.展开更多
We report the femtosecond time-resolved studies of room temperature exciton recombination and ultrafast stimulated emission dynamics in ZnO microcrystallite thin films.A free exciton photoluminescence lifetime of a fe...We report the femtosecond time-resolved studies of room temperature exciton recombination and ultrafast stimulated emission dynamics in ZnO microcrystallite thin films.A free exciton photoluminescence lifetime of a few tens of picoseconds and a decay time of a few picoseconds for the stimulated emission were observed.The relatively slow rise time(3ps)for the P band as the result of exciton-exciton scattering compared with the 0.8ps rise time for the N band attributed to electron-hole plasma recombination clearly distinguished the two stimulated emission processes.展开更多
文摘BACKGROUND Odontogenic maxillary sinusitis,often triggered by dental issues like periapical periodontitis,significantly contributes to chronic sinusitis,mainly affecting adults around 50 years old,emphasizing the need for a multidisciplinary diagnostic and treatment approach.AIM To investigate the therapeutic effect and clinical value of root canal therapy combined with nasal endoscopic surgery compared with simple root canal the-rapy in the treatment of severe odontogenic maxillary sinusitis caused by peria-pical periodontitis.METHODS The clinical data,diagnosis,and treatment of 200 patients with severe odonto-genic maxillary sinusitis caused by periapical periodontitis from October 2020 to October 2021 were analyzed retrospectively.Among them,63 patients were treated with simple root canal therapy as the control group,and 137 patients were treated with root canal therapy combined with nasal endoscopic surgery as the observation group.The therapeutic effect,Lund-Kennedy endoscopic score,paranasal sinus Lund-Mackay score,complication rate,recurrence rate,and patient satisfaction were compared between the two groups.RESULTS First,we compared the effective rates:23 cases were cured,22 were improved,and 8 were ineffective in the control group,yielding a total effective rate of 84.90%.Meanwhile,97 cases were cured,34 improved,and 6 were ineffective in the observation group,resulting in a total effective rate of 95.62%.The observation group had a higher total effective rate compared with the control group(P<0.05).Second,we compared the Lund–Kennedy endoscopic score.Before treatment,no significant difference(P>0.05)was observed in this score between the two groups.After treatment,the Lund–Kennedy endoscopic score decreased in both groups.The Lund–Kennedy endoscopic score of the observation group at 3 and 6 mo after treatment was lower compared to that of the control group(P<0.05).Third,we compared the Lund–Mackay score of paranasal sinuses.Before treatment,there was no significant difference in this score between the two groups(P>0.05).After treatment,the Lund–Mackay scores of paranasal sinuses decreased in both groups.The Lund–Mackay scores of paranasal sinuses in the observation group at 3 and 6 mo after treatment were lower compared to those of the control group(P<0.05).Fourth,we compared the incidence and recurrence rate of complications.Three months after treatment,no significant difference was found in the incidence and recurrence rate of complications between the observation group(6.56%)and the control group(9.52%)(P>0.05).However,6 mo after treatment,the incidence and recurrence rate of complications in the observation group(2.91%)was significantly higher compared to that of the control group(12.69%)(P<0.05).Fifth,we compared patient satisfaction.Six months after treatment,the patient satisfaction of the observation group(93.43%)was significantly better than that of the control group(84.12%)(P<0.05).CONCLUSION Root canal therapy combined with nasal endoscopic surgery has a good therapeutic effect on severe odontogenic maxillary sinusitis caused by periapical periodontitis,and it can reduce the injury of maxillary sinus mucosa and bone,and significantly reduce the incidence of complications and recurrence rate.Meanwhile,it has high patient satisfaction and remarkable therapeutic effect,which is suggested to be popularized and applied in clinic.
基金supported by the National Natu-ral Science Foundation of China(No.U2230126)the Natural Science Foundation of Zhejiang Province(No.LZ23E010001)+1 种基金This work was co-funded by the European Union under the Project Robotics and Advanced Industrial Production(Reg.No.CZ.02.01.01/00/22_008/0004590)supported by the Ministry of Education,Youth and Sports of the Czech Repub-lic through the e-INFRA CZ grant number ID:90140.Access to the computational infrastructure of the OP VVV funded Project No.CZ.02.1.01/0.0/0.0/16_019/0000765“Research Center for Informat-ics”and the use of the VESTA software[https://doi.org/10.1107/S0021889808012016]are also acknowledged.The authors thank the staffof HIRFL for the help with the irradiation experiment and the support of the Sharing Service Platform of CAS Large Re-search Infrastructures(2022-HIRFL-ZD-002017)。
文摘Cr coatings,as protective coatings of Zr-alloy fuel claddings,inevitably suffer from irradiation damage before they would possibly run into the accident condition.This study evaluates the radiation and oxidation tolerance of three Cr-based coatings with different microstructures(Cr,CrAlSi,and CrAlSiN)through He2+ion irradiation and 1200℃ steam oxidation.The Cr and CrAlSi coatings experienced significant structural degradation,characterized by He bubble aggregation and amplified Kirkendall effects at elevated temperatures.In contrast,the irradiated CrAlSiN coating maintained structural integrity without measurable irradiation hardening.Following annealing at 800℃ for 30 min,approximately 40%of injected He atoms were released,indicating a“self-healing”mechanism.The mechanism is attributed to uniformly distributed,low-density channels that act as sinks and release paths for irradiation-induced defects.Density functional theory simulations suggest that N atoms promote significant rearrangement of ions surrounding the free volume,inhibiting the formation of sites capable of trapping He atoms.Moreover,the CrAlSiN coating exhibited superior oxidation resistance compared to the Cr and CrAlSi coatings,even under high-temperature steam conditions.Notably,the irradiated CrAlSiN sample displayed a significantly thinner oxide scale compared to the pristine one(almost half),owing to a more protective oxide scale and rapid outward diffusion of Cr,Al,and Si through nanochannel veins.These findings illuminate the effects of structure and composition on irradiation and oxidation behavior in Cr-based coatings,offering insights for developing new-generation accident-tolerance fuel coatings for Zr-alloy claddings.
基金supported by the Special Project for Marine Economic Development of Department of Natural Resources of Guangdong Province(No.GDNRC[2024]25)National Natural Science Foundation of China(Nos.82274002,U20A20101)+1 种基金Guangdong Local Innovation Team Program(No.2019BT02Y262)Science and Technology Innovation Project of Guangdong Medical Products Administration(Nos.S2021ZDZ042,2023ZDZ06,2024-ZDZ08,2024A1515012477)。
文摘This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(GPA)and 13-hydroxyglucopiericidin A(13-OH-GPA).The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate.Rapid absorption of PA and GPAs in mice was observed,characterized by short half-lives and low bioavailability.Glycosides and hydroxyl groups significantly enhanced the absorption rate(13-OH-GPA>GPA>PA).PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes(CYPs)and uridine diphosphoglucuronosyl transferases(UGTs).Glucuronidation emerged as the primary metabolic pathway,with UGT1A7,UGT1A8,UGT1A9,and UGT1A10 demonstrating high elimination rates(30%-70%)for PA and GPAs.This rapid glucuronidation may contribute to the low bioavailability of GPAs.Despite its low bioavailability(2.69%),13-OH-GPA showed higher kidney distribution(19.8%)compared to PA(10.0%)and GPA(7.3%),suggesting enhanced biological efficacy in kidney diseases.Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability.In conclusion,this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
文摘阐述了零部件级释气率程控测试系统的研制思路与方法。以小孔流导法为理论依据,从程控角度出发,将PLC与上位机软件紧密结合,实现了对零部件释气率的全自动测试。该系统可自动生成具有关键信息的测试报告。同时,系统还具备全自动校准工艺,最大程度地保证了测试数据的准确性。控制系统通过PLC自动程序控制真空系统的启停,从而获取真空测试环境;上位机软件与质谱仪(Quadrupole Mass Spectrometer,QMS)进行通讯,采集QMS中的数据,并进行数据分析;上位机软件与PLC程序配合,可保证校准工艺以及测试工艺的自动运行。
基金Supported by Science&Technology Department of Sichuan Province(No.2021YFS0214).
文摘Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.However,studies on neuroprotective strategies for optic neuropathy have increased in recent years.Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy.Regenerative medicine research into the repair of optic nerve damage using stem cells has Received considerable attention.Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGCfriendly microenvironments through paracrine effects.This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury,raising the controversies and unresolved issues surrounding the future of stem cells.
文摘Dear Editor,The choice of surgical intervention for nanophthalmos patients with secondary angle-closure glaucoma poses a challenging decision for ophthalmologists.Because nanophthalmos patients who have undergone filtration surgery or other intraocular procedures are more susceptible to severe complications,including choroidal effusion,malignant glaucoma,and explosive choroidal hemorrhage,all of which can lead to vision loss[1].This dilemma is particularly pronounced in patients with shorter axial lengths.Micropulse transscleral laser therapy(M-TLT),also known as micropulse transscleral cyclophotocoagulation(MP-TSCPC),is a nonincisional laser therapy surgery for glaucoma[2].In 2015,Golan and Kurtz[3]were the first to report four patients with secondary angle-closure glaucoma in nanophthalmos with axial lengths ranging between 17 and 19 mm(mean 18 mm)who were successfully treated with M-TLT,and choroidal detachment was observed in all patients(recovery spontaneously in two patients and recovery after systemic steroid treatment in the other two),of which two had a slight decrease in visual acuity.
文摘Correction:Natural Products and Bioprospecting(2024)14:33 https://doi.org/10.1007/s13659-024-00455-x Following publication of the original article[1],the authors reported that the original version of this article unfortunately contained mistakes.Page 1,section“Abstract”,the originally published texts were:Despite low bioavailability(0.024%),N-hydap exhibited a higher distribution in the lungs(26.26%),accounting for its efficacy against SCLC.
基金supported by the grants from the Major State Basic Research Development Program of China(2012CB517902 and 2012CB517904)National Key Technology Research and Development Program of China(2012BAI03B00)+3 种基金Special Research Program of National Health and Family Planning Commission of China(201302002)International S&T Cooperation Program of China(2011DFA30670)National Natural Science Foundation of China(31571357/31771404)supported in part by research funding from AstraZeneca Innovation Center China and Wenzhou Medical University
文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.
基金supported by the National Natural Science Foundation of China(Nos.82274002,42376124)Marine Economy Development Project of Guangdong Province(GDNRC[2021]52)+1 种基金Hainan Provincial Natural Science Foundation of China(823CXTD393)Key-Area Research and Development Program of Guangdong Province(2023B1111050008)。
文摘N-Hydroxyapiosporamide(N-hydap),a marine product derived from a sponge-associated fungus,has shown promising inhibitory effects on small cell lung cancer(SCLC).However,there is limited understanding of its metabolic pathways and characteristics.This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s(CYPs)and UDP-glucuronosyltransferases(UGTs),as well as human/rat/mice microsomes,and also the pharmacokinetic properties by HPLC-MS/MS.Additionally,the cocktail probe method was used to investigate the potential to create drug-drug interactions(DDIs).N-Hydap was metabolically unstable in various microsomes after 1 h,with about 50%and 70%of it being eliminated by CYPs and UGTs,respectively.UGT1A3 was the main enzyme involved in glucuronidation(over 80%),making glucuronide the primary metabolite.Despite low bioavailability(0.024%),N-hydap exhibited a higher distribution in the lungs(26.26%),accounting for its efficacy against SCLC.Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity.Furthermore,N-hydap was found to affect the catalytic activity of drug metabolic enzymes(DMEs),particularly increasing the activity of UGT1A3,suggesting potential for DDIs.Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy,toxicity,and potential for DDIs.
文摘CJ Health Technology Co.has been an export-oriented supplier of fitness equipment,boasting leading technology innovation and manufacturing capabilities.However,in the process of expanding into the domestic market,the challenges of unclear market positioning and lack of brand awareness have emerged as major obstacles.To address these issues,a SWOT analysis was conducted to explore a suitable market positioning strategy for the CJ brand.The analysis reveals that the market demand for commercial fitness equipment is relatively saturated,with fierce competition.In contrast,the home fitness market represents a new blue ocean with promising development opportunities for the CJ brand.Leveraging excellent product quality,stringent quality control measures,and innovation-driven cutting-edge technology,it is recommended that CJ brand fitness equipment target young customers aged between 25 and 35 years old.Additionally,vigorously developing the home fitness product line is proposed to capitalize on this burgeoning market segment.
基金Supported by the National Natural Science Foundation of China under Grant No.69608002the Excellent Young Teacher's Foundation of the Minis try of Education.
文摘We report the femtosecond time-resolved studies of room temperature exciton recombination and ultrafast stimulated emission dynamics in ZnO microcrystallite thin films.A free exciton photoluminescence lifetime of a few tens of picoseconds and a decay time of a few picoseconds for the stimulated emission were observed.The relatively slow rise time(3ps)for the P band as the result of exciton-exciton scattering compared with the 0.8ps rise time for the N band attributed to electron-hole plasma recombination clearly distinguished the two stimulated emission processes.
