The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

Objective:To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice.Methods:In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17β-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot.Results:The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased ( P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group ( P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance ( P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences ( P=0.001, 0.001, 0.001), and CdS Ⅱ group 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group ( P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance ( P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group ( P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17β-HSD mRNA. There is a highly positive correlation between 17β-HSD mRNA levels, with statistically significant differences ( rs=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion:Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

Objective:To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice.Methods:In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17β-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot.Results:The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased ( P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group ( P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance ( P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences ( P=0.001, 0.001, 0.001), and CdS Ⅱ group 17β-HSD. The expression levels of 17β-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group ( P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance ( P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group ( P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17β-HSD mRNA. There is a highly positive correlation between 17β-HSD mRNA levels, with statistically significant differences ( rs=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion:Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

Background The increasing threats of air pollution and extreme weather have been widely recognized in recent years in China, but their individual and joint effects on cardio-cerebrovascular mortality are unclear. Objective This study aims to investigate the individual effects of and potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Methods We collected daily data on death counts of cardio-cerebrovascular diseases, concentrations of ambient air pollutants, and meteorological parameters in Guangzhou, Chinabetween 1 January 2006 and 31 December 2016. A generalized additive model with a Poisson distribution was conducted to assess the associations of oxidant pollutants and ambient temperature with cardio-cerebrovascular mortality risks. Bivariate response surface models and stratified analyses were further adopted to qualitatively and quantitatively examine the potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Results During the study period, the daily averages were 60.3 μg·m⁻³ for ozone (O₃), 50.9 μg·m⁻³ for combined atmospheric oxidant capacity (O_x), 32.5 μg·m⁻³ for nitrogen dioxide (NO₂), and 22.3℃ for ambient temperature. The average daily death counts of coronary and stroke diseases were 20 and 15, respectively. Per 10 μg·m⁻³ increment in O₃, O_x, and NO₂ were associated with increased coronary mortality risks (excess risk, ER) of 1.26% (95%CI: 0.79%-1.74%), 1.61% (95%CI: 0.99%-2.23%), and 1.33% (95%CI: 0.59%-2.07%), and with increased stroke mortality risks of 1.56% (95%CI: 1.04%-2.09%), 2.30% (95%CI: 1.60%-3.01%), and 2.93% (95%CI: 2.07%-3.79%) over cumulative lags of 2-5 days, respectively. The exposure-response relationships between ambient temperature and coronary and stroke mortality risks exhibited an inverse "J" shape, with the minimum mortality at temperatures of 25.7℃ for coronary disease and 27.3℃ for stroke. Our results further showed potentially synergic effects of higher temperatures and higher levels of O₃ and O_x exposures on coronary mortality risks, and the relative ER due to interactions was 0.103 (95%CI: 0.028-0.178) for O₃ and 0.079 (95%CI: 0.004-0.154) for O_x. We didn't find evidence of an interaction between oxidant pollutants and low temperature. Conclusion Short-term exposures to oxidant pollutants are associated with increased cardio-cerebrovascular mortality risks, and the interactive effects of high temperature and oxidant pollutants are synergistic in relation to cardio-cerebrovascular mortality risks.

Objective To investigate the association between Has‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer .Methods A systematic search of Pubmed ,EMBASE and Web of Science ,CNKI ,Wanfang was conducted for relevant studies .The odds ratios(OR) and 95% confidence intervals(95% CI) calculated by Stata12 .0 software were used to assess the asso‐ciation between Has‐miRNA‐149 polymorphism and risk of digestive tract cancer .The Q test ,I2 value and funnel plot were conduc‐ted to examine heterogeneity and publication bias ,respectively .Results A total of thirteen eligible studies containing 4 424 cases and 5 290 controls were included in this Meta analysis .There were significant relationships between Hsa‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer (Domina model CT+CC vs .TT ,OR=0 .915 ,95% CI:0 .840-0 .996 ,P=0 .040 ;Hetero‐zygous model CT vs .TT ,OR=0 .880 ,95% CI:0 .803 -0 .965 ,P=0 .007) .In the stratified analysis ,it was found that the risk of colorectal cancer decreased in patients carrying CC/CT genotypes(OR=0 .834 ,95% CI:0 .715-0 .972 ,P=0 .021) ,especially in A‐sians (CT+CC vs .TT ,OR=0 .894 ,95% CI:0 .818-0 .977 ,P=0 .013) ,while that was not found in the Caucasoids .Conclusion Has‐miRNA‐149 polymorphism is associated with the susceptibility of digestive tract cancer .The CC/CT genotypes may decrease the risk of digestive tract cancer ,especially in Asians .

Objective To compare the patency rate of percutaneous balloon angioplasty or stenting for restenosis of femoral-popliteal artery artificial vascular grafting.Method 78 cases of femoral-popliteal artery artificial vascular graft postoperative occlusion patients were divided into 2 groups:anastomotic balloon angioplasty group (36 cases) and stent angioplasty group (42 cases) after double-lumen catheter embolectomy.Patients in anastomotic balloon dilatation group were given balloon angioplasty only becaus fine narrow flow signals were seen in angiography.Patients in stenting group received balloon angioplasty followed by suitable caliber self-expanding stent placement.Patency rates were compared between the two groups after 12,36 months of interventional treatment.Results The patency rate in stenting group was higher than that of percutaneous balloon angioplasty group (x2 =7.422,P ＜ 0.05).Conclusions Balloon stenting angioplasty had advantages of high patency rate over balloon dilatation for the treatment of postoperative occlusion of femoral-popliteal artery grafting.

Objective To investigate the relation between polymorphism of NOS3 G894T and susceptibility of cancer .Methods Literatures under the inclusion and exclusion criteria about relation between polymorphism of NOS 3 G894T and susceptibility of cancer were collected by computer -based retrieval and manual retrieval .The pools ORs with 95% CI were calculated to assess the association strength between polymorphism of NOS 3 G894T and cancer risk by Meta methods .Sensitivity and publication bias were evaluated .Results 19 literatures with 7679 cases of cancer and 8180 cases as control group were included .The pooled result indica-ted that no significant association between its polymorphism and cancer (ORT versus G=1 .030 ,95% CI=0 .964 -1 .101 ;ORTT versus GG=1 .056 ,95% CI=0 .895-1 .245 ;ORTG versus GG=1 .045 ,95% CI=0 .977-1 .119 ;ORTT/TG versus GG=1 .047 , 95% CI=0 .981-1 .117 ;ORTT versus TG/GG=1 .005 ,95% CI=0 .900-1 .123) .No significant association was observed in sub-group analysis based on ethnicity ,cancer type ,and source of control group .Conclusion There was no relationship between NOS3 G894T polymorphism and cancer susceptibility .

Objective To evaluate short and medium term therapeutic effects of VIABAHN-covered stent in treat-ment of arteriosclerosis obliterans in lower extremity. Methods Among all 53 cases of arteriosclerosis obliterans in lower extremity with C/D TASC levels, 22 patients underwent VIABAHN-covered stent (stent group), while the other 31 patients were treated with femoral-popliteal artery bypass grafting surgery (graft group). The arterial patency rates were analyzed 3 and 6 months after the two different surgeries. Results The number of arterial patency cases were 28 (90.3%) at 3 months and 26 (83.9%) at 6 months in stent group while it is 22 (100%) at 3 months and 21 (95.5%) at 6 months in graft group. There were no significant differences in the arterial patency rate at 3 months and 6 months between the two different surger-ies (χ2 is 0.808 and 0.760 respectively, P>0.05). Conclusion VIABAHN-covered stent can be used as the preferred treat-ment for arteriosclerosis obliterans of lower extremity.