Succession changes of microbial community for inferring the time since deposition of saliva.

Saliva is a common biological examination material at crime scenes and has high application value in forensic case investigations. It can reflect the suspect's time of crime at the scene and provide evidence of the suspect's criminal facts. Even though many researchers have proposed their experimental protocols for estimating the time since deposition (TsD) of saliva, there is still a relative lack of research on the use of microorganisms to estimate TsD. In the current study, the succession change of microbial community in saliva with different TsD values was explored to discern the microbial markers related to TsD of saliva. We gathered saliva samples from six unrelated healthy Han individuals living in Guizhou, China and exposed these samples to indoor conditions at six time points (0, 1, 3, 7, 15, and 28 days). Temporal changes of microbial compositions in these samples were investigated by 16S rRNA sequencing (V3-V4 regions). By assessing temporal variation patterns of microbial abundance at the genus level, four bacteria (Brucella, Prevotella, Pseudomonas, and Fusobacterium) were observed to show good time dependence in these samples. In addition, the hierarchical clustering and principal co-ordinates analysis results revealed that these saliva samples could be classified into t-short (≤7 days) and t-long (>7 days) groups. In the end, the random forest model was developed to predict the TsD of these samples. For the model, the root mean square error, R2, and mean absolute error between predicted and actual TsD values were 1.5213, 0.9851, and 1.1969, respectively. To sum up, we identified TsD-related microbial markers in saliva samples, which could be viewed as valuable markers for inferring the TsD of saliva.

Ultraconserved elements from transcriptome and genome data provide insight into the phylogenomics of Sternorrhyncha (Insecta: Hemiptera).

Sternorrhyncha, one of the four major suborders of Hemiptera, is a phytophagous taxon inclusive of nearly 18 000 described species. The phylogenetic relationships within the taxon and the earliest-branching lineage of its infraorders remain incompletely understood. This study attempted to illuminate the phylogenetic relationships within Sternorrhyncha through the use of maximum likelihood, Bayesian inference and maximum parsimony analyses, employing ultraconserved element (UCE) data from 39 genomic and 62 transcriptomic datasets and thereby representing most families within the taxon. The probe set Hemiptera 2.7Kv1 was used to recover a total of 2731 UCE loci: from 547 to 1699 (with an average of 1084) across all genomic datasets and from 108 to 849 (with an average of 329) across all transcriptomic datasets. All three types of phylogenetic analyses employed in this study produced robust statistical support for Sternorrhyncha being a monophyletic group. The different methods of phylogenetic analysis produced inconsistent descriptions of topological structure at the infraorder level: while maximum likelihood and Bayesian inference analyses produced strong statistical evidence (100%) indicating the clade Psylloidea + Aleyrodoidea to be a sister of the clade Aphidoidea (Aphidomorpha) + Coccoidea (Coccomorpha), the maximum parsimony analysis failed to recover a similar result. Our results also provide detail on the phylogenetic relationships within each infraorder. This study presents the first use of UCE data to investigate the phylogeny of Sternorrhyncha. It also shows the viability of amalgamating genomic and transcriptomic data in studies of phylogenetic relationships, potentially highlighting a resource-efficient approach for future inquiries into diverse taxa through the integration of varied data sources.

Improving DNA barcoding library of armored scale insects (Hemiptera: Diaspididae) in China.

DNA barcoding is used to identify cryptic species, survey environmental samples, and estimate phyletic and genetic diversity. Armored scale insects are phytophagous insects and are the most species-rich taxa in the Coccoidea superfamily. This study developed a DNA barcode library for armored scale insect species collected from southern China during 2021-2022. We sequenced a total of 239 specimens, recognized as 50 morphological species, representing two subfamilies and 21 genera. Sequencing analysis revealed that the average G + C content of the cytochrome oxidase subunit I (COI) gene sequence was very low (~18.06%) and that the average interspecific divergence was 10.07% while intraspecific divergence was 3.20%. The intraspecific divergence value was inflated by the high intraspecific divergence in ten taxa, which may indicate novel species overlooked by current taxonomic treatments. All the Automated Barcode Gap Discovery, Assemble Species by Automatic Partitioning, Taxon DNA analysis and Bayesian Poisson Tree Process methods yielded largely consistent results, indicating a robust and credible species delimitation. Based on these results, an intergeneric distance threshold of ≤ 5% was deemed appropriate for the differentiation of armored scale insect species in China. This study establishes a comprehensive barcode library for the identification of armored scale insects, future research, and application.

Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), ß-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle "ACEI + BB + MRA" in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m2, 95% CI: -14.88 to -1.23 mL/m2) and ACEI + BB + SGLT-2i (-18.94 mL/m2, 95% CI: -36.97 to -0.61 mL/m2) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION: PROSPERO; No. CRD42022354792.

Forensic features and phylogenetic structure survey of four populations from southwest China via the autosomal insertion/deletion markers.

Insertion/Deletion (InDel) polymorphisms, characterized by their smaller amplicons, reduced mutation rates, and compatibility with the prevalent capillary electrophoresis (CE) platforms in forensic laboratories, significantly contribute to the advancement and application of genetic analysis. Guizhou province in China serves as an important region for investigating the genetic structure, ethnic group origins, and human evolution. However, DNA data and the sampling of present-day populations are lacking, especially about the InDel markers. Here, we reported data on 47 autosomal InDels from 592 individuals from four populations in Guizhou (Han, Dong, Yi, and Chuanqing). Genotyping was performed with the AGCU InDel 50 kit to evaluate their utility for forensic purposes and to explore the population genetic structure. Our findings showed no significant deviations from Hardy-Weinberg and linkage equilibriums. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) for each population demonstrated that the kit could be applied to forensic individual identification and was an effective supplement for parentage testing. Genetic structure analyses, including principal component analysis, multidimensional scaling, genetic distance calculation, STRUCTURE, and phylogenetic analysis, highlighted that the genetic proximity of the studied populations correlates with linguistic, geographical, and cultural factors. The observed genetic variances within four research populations were less pronounced than those discerned between populations across different regions. Notably, the Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi. These results underscore the potential of InDel markers in forensic science and provide insights into the genetic landscape and human evolution in multi-ethnic regions like Guizhou. Key points: InDel markers show promise for forensic individual identification and parentage testing via the AGCU InDel 50 kit.Genetic analysis of Guizhou populations reveals correlations with linguistic, geographical, and cultural factors.Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi.

Clickable X-ray Nanoprobes for Nanoscopic Bioimaging of Cellular Structures.

Synchrotron-based X-ray microscopy (XRM) has garnered widespread attention from researchers due to its high spatial resolution and excellent energy (element) resolution. Existing molecular probes suitable for XRM include immune probes and genetic labeling probes, enabling the precise imaging of various biological targets within cells. However, immune labeling techniques are prone to cross-interference between antigens and antibodies. Genetic labeling technologies have limited systems that allow express markers independently, and moreover, genetically encoded labels based on catalytic polymerization lack a fixed morphology. When applied to cell imaging, this can result in reduced localization accuracy due to the diffusion of labels within the cells. Therefore, both techniques face challenges in simultaneously labeling multiple biotargets within cells and achieving high-precision imaging. In this work, we applied the click reaction and developed a third category of imaging probes suitable for XRM, termed clickable X-ray nanoprobes (Click-XRN). Click-XRN consists of two components: an X-ray-sensitive multicolor imaging module and a particle-size-controllable morphology module. Efficient identification of intra- and extracellular biotargets is achieved through click reactions between the probe and biomolecules. Click-XRN possesses a controllable particle size, and its loading of various metal ions provides distinctive signals for imaging under XRM. Based on this, we optimized the imaging energy of Click-XRN with different particle sizes, enabling single-color and two-color imaging of the cell membrane, cell nucleus, and mitochondria with nanoscale spatial nanometers. Our work provides a potent molecular tool for investigating cellular activities through XRM.

Exploiting genomic tools for genetic dissection and improving the resistance to Fusarium stalk rot in tropical maize.

KEY MESSAGE: A stable genomic region conferring FSR resistance at ~250 Mb on chromosome 1 was identified by GWAS. Genomic prediction has the potential to improve FSR resistance. Fusarium stalk rot (FSR) is a global destructive disease in maize; the efficiency of phenotypic selection for improving FSR resistance was low. Novel genomic tools of genome-wide association study (GWAS) and genomic prediction (GP) provide an opportunity for genetic dissection and improving FSR resistance. In this study, GWAS and GP analyses were performed on 562 tropical maize inbred lines consisting of two populations. In total, 15 SNPs significantly associated with FSR resistance were identified across two populations and the combinedPOP consisting of all 562 inbred lines, with the P-values ranging from 1.99 × 10-7 to 8.27 × 10-13, and the phenotypic variance explained (PVE) values ranging from 0.94 to 8.30%. The genetic effects of the 15 favorable alleles ranged from -4.29 to -14.21% of the FSR severity. One stable genomic region at ~ 250 Mb on chromosome 1 was detected across all populations, and the PVE values of the SNPs detected in this region ranged from 2.16 to 5.18%. Prediction accuracies of FSR severity estimated with the genome-wide SNPs were moderate and ranged from 0.29 to 0.51. By incorporating genotype-by-environment interaction, prediction accuracies were improved between 0.36 and 0.55 in different breeding scenarios. Considering both the genome coverage and the threshold of the P-value of SNPs to select a subset of molecular markers further improved the prediction accuracies. These findings extend the knowledge of exploiting genomic tools for genetic dissection and improving FSR resistance in tropical maize.

Self-assembly of metal-polyphenolic network on biomass for enhanced organic contaminant capturing from water with a high cost-to-benefit ratio.

Nanomaterials present a vast potential as functional materials in environmental engineering. However, there are challenges with nanocomplex for recyclability, reliable/stable, and scale-up industrial integration. Here, a versatile, low-cost, stable and recycled easily metal-polyphenolic-based material carried by wood powder (bioCar-MPNs) adsorption platform was nano-engineered by a simple, fast self-assembly strategy, in which wood powder is an excellent substrate serving as a scaffold and stabilizer to prevent the nanocomplex from aggregating and is easier to recycle. Life cycle analysis highlights a green preparation process and environmental sustainability for bioCar-MPNs. The metal-polyphenolic nanocomplex coated on the wood surface in bioCar-MPNs presents a remarkable surface adsorption property (1829.4 mg/g) at a low cost (2.4 US dollars per 1000 g bioCar-MPNs) for organic dye. Quartz crystal microbalance analysis (QCM) demonstrates an existing strong affinity between polyphenols and organic dyes. Furthermore, Independent Gradient Model (IGM) and Hirshfeld surface analysis reveal the presence of the electrostatic interactions, π-π interactions, and hydrogen bonding. Meanwhile, adsorption efficiency of bioCar-MPNs maintains over 95% in the presence of co-existing ions (Na+, 0.5 M). Importantly, the reasonable utilization of biomass for water treatment can contribute to achieving the high-value and resource utilization of biomass materials.

Simultaneous determination of 28 illegal drugs in sewage by high throughput online SPE-ISTD-UHPLC-MS/MS.

This study developed an online solid-phase extraction ultra-high performance liquid chromatography-tandem mass spectrometry (Online-SPE-UHPLC-MS/MS) method for the analysis of 28 illegal drugs in sewage. To achieve this, 28 isotope internal standards (ISTDs) were added to 3 mL sewage samples, the pH was adjusted to 7-8 using hydrochloric acid or 20% ammonia water, followed by centrifugation, filtration, and analysis using UHPLC-MS/MS. The results indicated an excellent linearity of 1-300 ng L-1, and cotinine in the concentration range of 20-6000 ng L-1, linear correlation coefficient R2 > 0.995, with the limit of detection (LOD) of 0.01-6 ng L-1, and a limit of quantification (LOQ) of 0.1-20 ng L-1. The addition of three concentrates of low (2 ng L-1/40 ng L-1), medium (20 ng L-1/400 ng L-1), and high concentration (200 ng L-1/4000 ng L-1) demonstrated the matrix effect of the target compound between ± 22.0%. The extraction recovery was 70.0-119.4%, and a percent accuracy of 75.7-118.1%. Similarly, the intra- and inter-day precisions were 1.8-20.0% and 1.5-18.9%, respectively. The results cemented the sensitivity, accuracy, reliability, strong specificity, and reproducibility, which can be used to screen 28 illegal drugs in sewage for trace analysis.

Application and evaluation of artificial intelligence 3D preoperative planning software in developmental dysplasia of the hip.

BACKGROUND: Accurate preoperative planning is crucial for successful total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH). The aim of this study was to compare the accuracy of an artificial intelligence-assisted three-dimensional (3D) planning system (AIHIP) with two-dimensional templates in predicting acetabular cup size in THA for DDH. METHOD: This study retrospectively analyzed image data from 103 DDH patients who had THA between May 2019 and August 2023. AIHIP was used for 3D planning, and two-dimensional (2D) templates were used by two experienced surgeons. Accuracy was assessed by comparing predicted and actual cup sizes, and potential factors affecting accuracy were analyzed, including gender, side, BMI, and dysplasia classification. RESULTS: AIHIP had higher accuracy in predicting the acetabular cup size compared to the 2D template. Within ± 0 size, AIHIP's accuracy was 84.1%, while the 2D template's was 64.0% (p < 0.05). Within ± 1 size, AIHIP's accuracy was 95.1%, while the 2D template's was 81.1% (p < 0.05). Accuracy was unaffected by gender, side, or BMI but was by DDH classification. In subgroup analysis, AIHIP's mean absolute error (0.21 ± 0.54) was significantly lower than the 2D template's (0.62 ± 0.95) for Crowe II and Crowe III (p < 0.05). CONCLUSION: AIHIP is superior to 2D templates in predicting the acetabular cup size accurately for THA in DDH patients. AIHIP may be especially beneficial for Crowe II and III DDH patients, as 2D templates may not accurately predict cup size in these cases.

Electrospun multi-chamber core-shell nanofibers and their controlled release behaviors: A review.

Core-shell structure is a concentric circle structure found in nature. The rapid development of electrospinning technology provides more approaches for the production of core-shell nanofibers. The nanoscale effects and expansive specific surface area of core-shell nanofibers can facilitate the dissolution of drugs. By employing ingenious structural designs and judicious polymer selection, specialized nanofiber drug delivery systems can be prepared to achieve controlled drug release. The synergistic combination of core-shell structure and materials exhibits a strong strategy for enhancing the drug utilization efficiency and customizing the release profile of drugs. Consequently, multi-chamber core-shell nanofibers hold great promise for highly efficient disease treatment. However, little attention concentration is focused on the effect of multi-chamber core-shell nanofibers on controlled release of drugs. In this review, we introduced different fabrication techniques for multi-chamber core-shell nanostructures, including advanced electrospinning technologies and surface functionalization. Subsequently, we reviewed the different controlled drug release behaviors of multi-chamber core-shell nanofibers and their potential needs for disease treatment. The comprehensive elucidation of controlled release behaviors based on electrospun multi-chamber core-shell nanostructures could inspire the exploration of novel controlled delivery systems. Furthermore, once these fibers with customizable drug release profiles move toward industrial mass production, they will potentially promote the development of pharmacy and the treatment of various diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Thermal stress coupling mechanism during nanosecond impulse delay for the synergistic study of continuous-nanosecond combined laser removal of the rubber layer on a concrete surface.

Based on the principle of laser ablation and elastic vibration effect, a model of continuous nanosecond combined laser removal of rubber marks on a concrete surface was established. The model can explain the evolution of temperature, stress, and removal depth on time and laser energy density during laser cleaning. The results show that the theoretical adsorption force between the rubber layer and the concrete base is approximately 3.88×10-9 N. The continuous laser cleaning threshold is 561.31J/c m 2. In the combined laser, the continuous laser is 534.41J/c m 2, and the nanosecond laser is 0.35J/c m 2. As the delay time between the 2 ns laser beams increases, the maximum peak in the temperature curve gradually decreases. The optimal cleaning delay was obtained as Δ t=0.65S. The peak temperature at the characteristic position (0 µm, 0 µm) is 592.13 K, which is lower than the vaporization temperature of the rubber layer. The thermal stress values generated at this characteristic position exceed the adsorption stress values, indicating that the elastic removal mechanism is the main removal mechanism at the junction between the rubber layer and the concrete substrate.

Potentials of Milk-Derived Extracellular Vesicles as Carriers for Oral Delivery of Active Phytoconstituents.

Extracellular vesicles (EVs) play a crucial role in intercellular communication and have the potential to serve as in vivo carriers for delivering active molecules. The biocompatibility advantages of EVs over artificial nanocarriers create new frontiers for delivering modern active molecules. Milk is a favorable source of EVs because of its high bioavailability, low immunogenicity, and commercial producibility. In this study, we analyzed the advantages of milk-derived EVs in the oral delivery of active molecules, discussed their research progress in delivering active phytoconstituents, and summarized the necessary technologies and critical unit operations required for the development of an oral delivery system based on EVs. The review aims to provide innovative ideas and fundamental quality control guidelines for developing the next-generation oral drug delivery system based on milk-derived EVs. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Prolonged efficacy of cefazolin in intraosseous regional prophylaxis for total knee arthroplasty: a rabbit model study.

BACKGROUND: A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. METHODS: Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. RESULTS: The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. CONCLUSIONS: Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Analysis of maternal genetic structure of mitochondrial DNA control region from Tai-Kadai-speaking Buyei population in southwestern China.

BACKGROUND: Even though the Buyei are a recognised ethnic group in southwestern China, there hasn't been much work done on forensic population genetics, notably using mitochondrial DNA. The sequences and haplogroups of mitochondrial DNA control regions of the Buyei peoples were studied to provide support for the establishment of a reference database for forensic DNA analysis in East Asia. METHODS AND RESULTS: The mitochondrial DNA control region sequences of 200 Buyei individuals in Guizhou were investigated. The haplotype frequencies and haplogroup distribution of the Buyei nationality in Guizhou were calculated. At the same time, the paired Fst values of the study population and other populations around the world were computed, to explore their genetic polymorphism and population relationship. A total of 179 haplotypes were detected in the Buyei population, with frequencies of 0.005-0.015. All haplotypes were assigned to 89 different haplogroups. The haplotype diversity and random matching probability were 0.999283 and 0.0063, respectively. The paired Fst genetic distances and correlation p-values among the 54 populations revealed that the Guizhou Buyei was most closely related to the Henan Han and the Guizhou Miao, and closer to the Hazara population in Pakistan and the Chiang Mai population. CONCLUSIONS: The study of mitochondrial DNA based on the maternal genetic structure of the Buyei nationality in Guizhou will benefit the establishment of an East Asian forensic DNA reference database and provide a reference for anthropological research in the future.

HHCDB: a database of human heterochromatin regions.

Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.

Electrospun Core-Sheath Nanofibers with a Cellulose Acetate Coating for the Synergistic Release of Zinc Ion and Drugs.

Precisely modulating the synergistic release behavior of multiple bioactive substances has emerged as a formidable challenge in recent years. In this work, we successfully prepared core-sheath nanofibers, where a thin cellulose acetate (CA) coating enrobed the core. Curcumin (Cur) was encapsulated in the core layer as a model drug, while zinc oxide (ZnO) nanoparticles were loaded on the sheath layer. The prepared fiber exhibited a straight cylindrical morphology containing nanoparticles, and the distinct core-sheath nanostructure was demonstrated through transmission electron microscopy (TEM). X-ray diffraction (XRD) and Fourier transform infrared (FTIR) were conducted to study the physical state and compatibility among CA, Cur, and ZnO. Drug release data indicated that core-sheath nanofibers were able to decelerate the rate of drug release, and the thickness of the sheath layer increased in the presence of ZnO particles. Most remarkably, these core-sheath nanofibers exhibited the remarkable ability to sustain the release of drugs and zinc ion (Zn2+), the two-day synergistically release behavior leading to a significant increase in cell proliferation. This material preparation strategy for the synergistic and controlled release of two bioactive substances is instructive for the exploration of innovative and versatile drug delivery systems.

Causal effect of air pollution on the risk of cardiovascular and metabolic diseases and potential mediation by gut microbiota.

BACKGROUND: Epidemiological studies have explored the relationship between air pollution and cardiovascular and metabolic diseases (CVMDs). Accumulating evidence has indicated that gut microbiota deeply affects the risk of CVMDs. However, the findings are controversial and the causality remains uncertain. To evaluate whether there is the causal association of four air pollutants with 19 CVMDs and the potential effect of gut microbiota on these relationships. METHODS: Genetic instruments for particulate matter (PM) with aerodynamic diameter < 2.5 µm (PM2.5), <10 µm (PM10), PM2.5 absorbance, nitrogen oxides (NOx) and 211 gut microbiomes were screened. Univariable Mendelian randomization (UVMR) was used to estimate the causal effect of air pollutants on CVMDs in multiple MR methods. Additionally, to account for the phenotypic correlation among pollutant, the adjusted model was constructed using multivariable Mendelian randomization (MVMR) analysis to strength the reliability of the predicted associations. Finally, gut microbiome was assessed for the mediated effect on the associations of identified pollutants with CVMDs. RESULTS: Causal relationships between NOx and angina, heart failure and hypercholesterolemia were observed in UVMR. After adjustment for air pollutants in MVMR models, the genetic correlations between PM2.5 and hypertension, type 2 diabetes mellitus (T2DM) and obesity remained significant and robust. In addition, genus-ruminococcaceae-UCG003 mediated 7.8 % of PM2.5-effect on T2DM. CONCLUSIONS: This study firstly provided the genetic evidence linking air pollution to CVMDs and gut microbiota may mediate the association of PM2.5 with T2DM. Our findings highlight the significance of air quality in CVMDs risks and suggest the potential of modulating intestinal microbiota as novel therapeutic targets between air pollution and CVMDs.