Proteins are the key players in many cellular processes. Their composition, trafficking, and interactions underlie the dynamic processes of life. Furthermore, diseases are frequently accompanied by malfunction of prot...Proteins are the key players in many cellular processes. Their composition, trafficking, and interactions underlie the dynamic processes of life. Furthermore, diseases are frequently accompanied by malfunction of proteins at multiple levels. Understanding how biological processes are regulated at the protein level is critically important to understanding the molecular basis for diseases and often shed light on disease prevention, diagnosis, and treatment. With rapid advances in mass spectrometry(MS)instruments and experimental methodologies, MS-based proteomics has become a reliable and essential tool for elucidating biological processes at the protein level. Over the past decade, we have witnessed great expansion of knowledge of human diseases with the application of MS-based proteomic technologies, which has led to many exciting discoveries. Herein we review the recent progress in MS-based proteomics in biomedical research, including that in establishing disease-related proteomes and interactomes. We also discuss how this progress will benefit biomedical research and clinical diagnosis and treatment of disease.展开更多
Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 a...Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 and a half years and recorded the air temperature,precipitation,and nutrient content in edible vegetation at the sampling site.After conducting 16S rRNA and shotgun metagenomic sequencing,we found that the highest alpha diversity,the relative abundance of Firmicutes,and the simplest co-occurrence network occurred in winter,whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring.The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn,respectively.Air temperature,precipitation,and the contents of crude protein,crude fiber,and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota.Diet contributed more to microbial variation than climatic factors.Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer,while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring.These microbial variations were related to the changes in dietary nutrition,indicating that gut microbiota of plateau pika contribute to the efficient use of food resources.This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.展开更多
Rapeseed is widely grown in China as an important oil crop. In this study, Shotgun lipidomic methodology based on tandem mass spectrometry but without liquid chromatography was established for simple lipids analysis s...Rapeseed is widely grown in China as an important oil crop. In this study, Shotgun lipidomic methodology based on tandem mass spectrometry but without liquid chromatography was established for simple lipids analysis such as mono-, di-and triacylglycerols(MAGs, DAGs and TAGs) and the derivatives such as free fatty acids(FFAs). Six varieties of rapeseeds belonging to 3 types(B. juncea, B. campestris and B. oleracea) from different areas of China were investigated, with 59 TAG species, 10 DAG species, 5 MAG species and 6 FFA species identified. It was found that erucic acid was mainly present in the form of TAG 62:4(22:1/18:2/22:1), TAG 62:3(22:1/18:1/22:1), and TAG 62:5(22:1/18:3/22:1) in high erucic acid rapeseed oils, while oleic acid was mainly present in the form of TAG 54:2(18:0/18:1/18:1), and TAG 54:4(18:1/18:2/18:1) in high oleic acid rapeseed oils. It was difficult for DAG, MAG and FFA quantification due to their low content with high background content of TAGs. Results showed that the main differences in lipids were not derived from the types of rapeseed, but directly related to varieties.展开更多
The ballistics equations for spherical pellets in free flight are simplified through appropriate scaling of the pellet velocity and pellet distance. Two different drag coefficient curves are averaged to yield a single...The ballistics equations for spherical pellets in free flight are simplified through appropriate scaling of the pellet velocity and pellet distance. Two different drag coefficient curves are averaged to yield a single curve applicable to shot pellets and round balls. The resulting S-shaped drag coefficient curve is approximated by three straight-line segments. The scaled ballistics equations are then solved exactly and simple formulas are found for the velocity and flight time with respect to trajectory distance. The formulas are applicable to spherical shot pellets and round balls of any composition under any atmospheric conditions. The formulas are amenable to quick and easy computation and may also serve as an aid in understanding and comparing black-box ballistics calculators. For shotshell ballistics, an important assumption in the present investigation is that the pellets are moving as single, free spheres and not as a dense cloud or in a shot column, in particular, the pellets are not interacting during flight. Therefore, the formulas are most appropriate for single round balls, for large shot sizes, and for pellets of small shot size fired from open chokes. The formulas are clear and accessible, and can be implemented by military or law enforcement personnel as well as hunters and shooters. This work differs from previous investigations in that accurate ballistics formulas are derived for spherical projectiles of shotguns and muzzleloaders using realistic drag coefficients.展开更多
Proteome-wide Amino aCid and Elemental composition （PACE） analysis is a novel and informative way of interrogating the proteome. The PACE approach consists of in silico decompo- sition of proteins detected and quant...Proteome-wide Amino aCid and Elemental composition （PACE） analysis is a novel and informative way of interrogating the proteome. The PACE approach consists of in silico decompo- sition of proteins detected and quantified in a proteomics experiment into 20 amino acids and five elements （C, H, N, O and S）, with protein abundances converted to relative abundances of amino acids and elements. The method is robust and very sensitive; it provides statistically reliable differ- entiation between very similar proteomes. In addition, PACE provides novel insights into prote- ome-wide metabolic processes, occurring, e.g., during cell starvation. For instance, both Escherichia coli and Synechocystis down-regulate sulfur-rich proteins upon sulfur deprivation, but E. coli preferentially down-regulates cysteine-rich proteins while Synechocystis mainly down- regulates methionine-rich proteins. Due to its relative simplicity, flexibility, generality and wide applicability, PACE analysis has the potential of becoming a standard analytical tool in proteomics.展开更多
The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon bi...The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis.Human or mouse colon biopsies were divided into two groups,with one group undergoing host DNA depletion and the other serving as the control.Host DNA was removed through differential lysis of mammalian and bacterial cells before sequencing.The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses.Removing host DNA enhanced bacterial sequencing depth and improved species discovery,increasing bacterial reads by 2.46±0.20 folds while reducing host reads by 6.80%±1.06%.Moreover,2.40 times more of bacterial species were detected after host DNA depletion.This was confirmed from mouse colon tissues,increasing bacterial reads by 5.46±0.42 folds while decreasing host reads by 10.2%±0.83%.Similarly,significantly more bacterial species were detected in the mouse colon tissue upon host DNA depletion(P<0.001).Furthermore,an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues(P<0.001).Our optimized method of host DNA depletion improves the sensitivity of shotgun metagenomic sequencing in bacteria detection in the biopsy,which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.展开更多
The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as w...The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenorrhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.展开更多
The vaginal microbiota is less complex than the gut microbiota,and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health.Oral probiotics have been suggested as pro...The vaginal microbiota is less complex than the gut microbiota,and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health.Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population.In this study,60 Chinese women were followed for over a year before,during,and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14.Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina.Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis.The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year,which was not affected by probiotic intake,whereas in the dysbiosis group,the microbiota was more diverse and changed markedly over time.Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics,indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis,providing opportunities for targeted and personalized microbiome reconstitution.展开更多
文摘Proteins are the key players in many cellular processes. Their composition, trafficking, and interactions underlie the dynamic processes of life. Furthermore, diseases are frequently accompanied by malfunction of proteins at multiple levels. Understanding how biological processes are regulated at the protein level is critically important to understanding the molecular basis for diseases and often shed light on disease prevention, diagnosis, and treatment. With rapid advances in mass spectrometry(MS)instruments and experimental methodologies, MS-based proteomics has become a reliable and essential tool for elucidating biological processes at the protein level. Over the past decade, we have witnessed great expansion of knowledge of human diseases with the application of MS-based proteomic technologies, which has led to many exciting discoveries. Herein we review the recent progress in MS-based proteomics in biomedical research, including that in establishing disease-related proteomes and interactomes. We also discuss how this progress will benefit biomedical research and clinical diagnosis and treatment of disease.
基金supported by the Grant from CAS No.152111KYSB20160089Qinghai innovation platform construction project by Chinese Academy of Sciences(2021-ZJ-Y01)+2 种基金the project of western light for interdisciplinary teamScience and Technology Department of Qinghai Province Major Project“Sanjiangyaun National Park Animal Genome Program”the Natural Science Foundation of Qinghai Province(2019-ZJ-7024).
文摘Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 and a half years and recorded the air temperature,precipitation,and nutrient content in edible vegetation at the sampling site.After conducting 16S rRNA and shotgun metagenomic sequencing,we found that the highest alpha diversity,the relative abundance of Firmicutes,and the simplest co-occurrence network occurred in winter,whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring.The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn,respectively.Air temperature,precipitation,and the contents of crude protein,crude fiber,and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota.Diet contributed more to microbial variation than climatic factors.Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer,while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring.These microbial variations were related to the changes in dietary nutrition,indicating that gut microbiota of plateau pika contribute to the efficient use of food resources.This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.
基金supported by National Natural Science Foundation of China(Grant No 21105119)Research Foundation of the Director General of Oil Crops Research Institute,Chinese Academy of Agricultural Sciences
文摘Rapeseed is widely grown in China as an important oil crop. In this study, Shotgun lipidomic methodology based on tandem mass spectrometry but without liquid chromatography was established for simple lipids analysis such as mono-, di-and triacylglycerols(MAGs, DAGs and TAGs) and the derivatives such as free fatty acids(FFAs). Six varieties of rapeseeds belonging to 3 types(B. juncea, B. campestris and B. oleracea) from different areas of China were investigated, with 59 TAG species, 10 DAG species, 5 MAG species and 6 FFA species identified. It was found that erucic acid was mainly present in the form of TAG 62:4(22:1/18:2/22:1), TAG 62:3(22:1/18:1/22:1), and TAG 62:5(22:1/18:3/22:1) in high erucic acid rapeseed oils, while oleic acid was mainly present in the form of TAG 54:2(18:0/18:1/18:1), and TAG 54:4(18:1/18:2/18:1) in high oleic acid rapeseed oils. It was difficult for DAG, MAG and FFA quantification due to their low content with high background content of TAGs. Results showed that the main differences in lipids were not derived from the types of rapeseed, but directly related to varieties.
文摘The ballistics equations for spherical pellets in free flight are simplified through appropriate scaling of the pellet velocity and pellet distance. Two different drag coefficient curves are averaged to yield a single curve applicable to shot pellets and round balls. The resulting S-shaped drag coefficient curve is approximated by three straight-line segments. The scaled ballistics equations are then solved exactly and simple formulas are found for the velocity and flight time with respect to trajectory distance. The formulas are applicable to spherical shot pellets and round balls of any composition under any atmospheric conditions. The formulas are amenable to quick and easy computation and may also serve as an aid in understanding and comparing black-box ballistics calculators. For shotshell ballistics, an important assumption in the present investigation is that the pellets are moving as single, free spheres and not as a dense cloud or in a shot column, in particular, the pellets are not interacting during flight. Therefore, the formulas are most appropriate for single round balls, for large shot sizes, and for pellets of small shot size fired from open chokes. The formulas are clear and accessible, and can be implemented by military or law enforcement personnel as well as hunters and shooters. This work differs from previous investigations in that accurate ballistics formulas are derived for spherical projectiles of shotguns and muzzleloaders using realistic drag coefficients.
基金the Swedish Research Council(Grant No.2009-4103)
文摘Proteome-wide Amino aCid and Elemental composition （PACE） analysis is a novel and informative way of interrogating the proteome. The PACE approach consists of in silico decompo- sition of proteins detected and quantified in a proteomics experiment into 20 amino acids and five elements （C, H, N, O and S）, with protein abundances converted to relative abundances of amino acids and elements. The method is robust and very sensitive; it provides statistically reliable differ- entiation between very similar proteomes. In addition, PACE provides novel insights into prote- ome-wide metabolic processes, occurring, e.g., during cell starvation. For instance, both Escherichia coli and Synechocystis down-regulate sulfur-rich proteins upon sulfur deprivation, but E. coli preferentially down-regulates cysteine-rich proteins while Synechocystis mainly down- regulates methionine-rich proteins. Due to its relative simplicity, flexibility, generality and wide applicability, PACE analysis has the potential of becoming a standard analytical tool in proteomics.
基金supported by the National Key R&D Program of China(Grant Nos.2020YFA0509200 and 2020YFA0509203)the RGC Theme-based Res Scheme Hong Kong,China(Grant No.T21-705/20-N)+2 种基金the RGC Collaborative Research Fund,China(Grant Nos.C4039-19GF and C7065-18GF)the RGC-GRF Hong Kong,China(Grant No.14163817)the Vice-Chancellor’s Discretionary Fund Chinese University of Hong Kong,China.
文摘The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis.Human or mouse colon biopsies were divided into two groups,with one group undergoing host DNA depletion and the other serving as the control.Host DNA was removed through differential lysis of mammalian and bacterial cells before sequencing.The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses.Removing host DNA enhanced bacterial sequencing depth and improved species discovery,increasing bacterial reads by 2.46±0.20 folds while reducing host reads by 6.80%±1.06%.Moreover,2.40 times more of bacterial species were detected after host DNA depletion.This was confirmed from mouse colon tissues,increasing bacterial reads by 5.46±0.42 folds while decreasing host reads by 10.2%±0.83%.Similarly,significantly more bacterial species were detected in the mouse colon tissue upon host DNA depletion(P<0.001).Furthermore,an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues(P<0.001).Our optimized method of host DNA depletion improves the sensitivity of shotgun metagenomic sequencing in bacteria detection in the biopsy,which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.
文摘The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenorrhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
文摘The vaginal microbiota is less complex than the gut microbiota,and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health.Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population.In this study,60 Chinese women were followed for over a year before,during,and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14.Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina.Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis.The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year,which was not affected by probiotic intake,whereas in the dysbiosis group,the microbiota was more diverse and changed markedly over time.Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics,indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis,providing opportunities for targeted and personalized microbiome reconstitution.
