[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

Epidemiological characteristics of human- and chicken-derived CTX-M-type extended-spectrum ß-lactamase-producing Escherichia coli from China.

Bacterial resistance to ß-lactams is mainly attributed to CTX-M-type extended-spectrum ß-lactamases (ESBLs). However, the predominant sequence type (ST) of blaCTX-M-carrying Escherichia coli (blaCTX-M-Ec) in chickens, an important food animal, in China and its contribution to human ß-lactam resistance are not investigated. In this study, approximately 1808 chicken-derived strains collected from 10 provinces from 2012 to 2020 were screened for blaCTX-M-Ec, and 222 blaCTX-M-Ec were identified. Antimicrobial susceptibility tests, whole genome sequencing and conjugation experiment were performed. All quality-controlled 136 chicken-derived blaCTX-M-Ec and 1193 human-derived blaCTX-M-Ec genomes were downloaded from NCBI and EnteroBase to comprehensively analyze the prevalence of blaCTX-M-Ec in China. blaCTX-M-55 (153/358, 42.7% in chicken isolates; 312/1193, 26.2% in human isolates) and blaCTX-M-14 (92/358, 25.7% in chicken isolates; 450/1193, 37.7% in human isolates) were dominant in blaCTX-M-Ec. The STs of blaCTX-M-Ec were diverse and scattered, with ST155 (n = 21) and ST152 (n = 120) being the most abundant in chicken- and human-derived isolates, respectively. Few examples indicated that chicken- and human-derived blaCTX-M-Ec have 10 or less core genome single nucleotide polymorphisms (cgSNPs). Genetic environment analysis indicated that ISEcp1, IS26 and IS903B were closely associated with blaCTX-M transfer. The almost identical pc61-55 and pM-64-1161 indicated the possibility of plasmid-mediated transmission of blaCTX-M between humans and chickens. Although the genomes of most blaCTX-M-Ec isolated from chickens and humans were quite different, the prevalence and genetic environment of blaCTX-M variants in both hosts were convergent. CTX-M-mediated resistance is more likely to spread through horizontal gene transmission than bacterial clones.

Study on the thermal behaviour of spontaneous combustion of open-pit minerals.

To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.

Whole-genome sequencing of Escherichia coli from retail meat in China reveals the dissemination of clinically important antimicrobial resistance genes.

Escherichia coli is one of the important reservoirs of antimicrobial resistance genes (ARG), which often causes food-borne diseases and clinical infections. Contamination with E. coli carrying clinically important antimicrobial resistance genes in retail meat products can be transmitted to humans through the food chain, posing a serious threat to public health. In this study, a total of 330 E. coli strains were isolated from 464 fresh meat samples from 17 food markets in China, two of which were identified as enterotoxigenic and enteropathogenic E. coli. Whole genome sequencing revealed the presence of 146 different sequence types (STs) including 20 new STs, and 315 different clones based on the phylogenetic analysis, indicating the high genetic diversity of E. coli from retail meat products. Antimicrobial resistance profiles showed that 82.42 % E. coli were multidrug-resistant strains. A total of 89 antimicrobial resistance genes were detected and 12 E. coli strains carried clinically important antimicrobial resistance genes blaNDM-1, blaNDM-5, mcr-1, mcr-10 and tet(X4), respectively. Nanopore sequencing revealed that these resistance genes are located on different plasmids with the ability of horizontal transfer, and their genetic structure and environment are closely related to plasmids isolated from humans. Importantly, we reported for the first time the presence of plasmid-mediated mcr-10 in E. coli from retail meat. This study revealed the high genetic diversity of food-borne E. coli in retail meat and emphasized their risk of spreading clinically important antimicrobial resistance genes.

Novel multidrug resistance genomic islands and transposon carrying blaVEB-1 identified in mcr-positive Aeromonas strains from raw meat in China.

OBJECTIVES: To characterize the genetic environments of ESBL gene blaVEB-1 in mcr-positive Aeromonas strains from raw meat in China. METHODS: Whole genomes of Aeromonas strains were sequenced using the Illumina or Nanopore platforms. Genetic environments of blaVEB-1 were analysed using the BLAST program. RESULTS: The blaVEB-1 gene was detected in five Aeromonas strains carrying the mcr-7-like gene. WGS revealed that all blaVEB-1 genes were located on Aeromonas chromosome, and were carried by two novel different genomic islands named Aeromonas veronii genomic islands AveGI1 and AveGI2, as well as one transposon named Tn7690. AveGI1 is a new member of the Salmonella genomic island 1 family, incorporated into the 3'-end of mnmE (trmE). AveGI2 is a novel genomic island that has a size of 23 180 bp and is incorporated into the 3'-end of syd. The MDR regions of AveGI1 and AveGI2 are two different class 1 integrons containing 10 and five resistance genes, respectively. Tn7690 is a Tn1722 derivative containing In4-type integron and Tn5393, which harbours 10 resistance genes and integrates into different positions on the chromosomes of three strains with the capacity for mobility. CONCLUSIONS: We report chromosomally located novel MDR genomic islands and transposon that carry blaVEB-1 in mcr-positive Aeromonas strains. These genetic elements may mediate the spread of blaVEB-1 in Aeromonas, and may also evolve by capturing new antimicrobial resistance genes or other mobile genetic elements.

Differential analysis of IBV-infected primary chicken embryonic fibroblasts and immortalized DF-1.

Infectious bronchitis virus (IBV), the causative agent of infectious bronchitis, is responsible for major economic losses in the poultry industry worldwide. While IBVs can usually be passaged in primary chicken embryonic fibroblasts (CEFs), most of the wild ones cannot adapt to passaged cell lines. In this study, the wild strain CK/CH/MY/2020 was used to infect primary CEF and immortalize DF-1 CEF cells. Results indicated that IBV was able to cause lesions and pass onto CEF, but not DF-1. Indeed, the virus could enter DF-1 cells and synthesize the associated structural gene but could not assemble into complete viral particles for release. Furthermore, transcriptome sequencing analysis showed significant differences in gene expression between CEF and DF-1 cells after viral infection, although the corresponding antiviral responses could be activated in both cell types. The biggest difference was in terms of the amino acid biosynthesis pathway and the cytokine receptor interaction pathway, which were significantly and specifically activated in CEF. This could actually explain why intact viruses can be assembled but not in DF-1. In addition, SLBP and P2RX7 affect the replication of IBV's structural genes to some extent. Overall, IBV can enter CEF and DF-1 cells, but the complex intracellular cytokine interactions affect the assembly and release of viral particles. The insight will be useful for the study of IBV through in vitro transmission and pathogenesis. IMPORTANCE: Infectious bronchitis virus (IBV) is responsible for high morbidity and mortality as well as substantial economic losses worldwide. Transcriptome sequencing of IBV-infected chicken embryonic fibroblast and DF-1 cells revealed that the virus elicits antiviral immunity in cells after viral infection, but IBV cannot activate DF-1 cells to produce sufficient amounts of viral structures to assemble into complete virions, which may be caused by the interactions between cytokines. The study of IBV cellular adaptations is important for vaccine development and investigation of the pathogenesis of IBV.

Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in Proteus mirabilis isolated from China, 2018-2020.

Proteus mirabilis can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of P. mirabilis were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive P. mirabilis exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to Escherichia coli EC600 with a frequency of 2.0 × 10-7 to 6.0 × 10-5. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICEPmiChnHBRJC2 carries erm (42), which have never been found within an SXT/R391 ICE in P. mirabilis, and ICEPmiChnSC1111 carries 19 ARGs, including clinically important cfr, blaCTX-M-65, and aac(6')-Ib-cr, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICEPmiChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICEPmiChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in P. mirabilis.IMPORTANCEThe spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in Proteus mirabilis, which can transfer ARGs to other hosts. The study found that all of the P. mirabilis strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.

Analysis of the effect of 60Co irradiation sterilization on the chemical composition of volatile organic compounds in Rhizoma Acori Tatarinowii using GC-IMS.

The volatile organic compounds (VOCs) of Rhizoma Acori Tatarinowii were extracted via steam distillation and then irradiated with 60Co-γ rays, in which doses of 60Co-γ 0, 5, and 10 kGy were selected to irradiate the VOCs. Finally, gas chromatography-ion mobility spectrometry (GC-IMS) was used to compare the differences between the VOCs, and then qualitatively analyse the components and contents of each part of the VOCs The results showed that under the three irradiation doses of 60Co-γ 0, 5 and 10 kGy, the VOCs of unirradiated and 5 kGy-irradiated samples were closer, and the samples irradiated at a 10 kGy dose were quite different from the other two components, meaning that when the calamus medicinal materials were sterilised by means of 60Co irradiation, the dose of 5 kGy was closer to the original compound content of the medicinal materials.

Investigation of 60Co Irradiation on the Volatile Organic Compounds from Finger Citron (Citri Sarcodactylis Fructus) Using GC-IMS.

In recent years, as the desire for a healthy lifestyle has become more widespread, consumers are gaining an increasing appreciation for safe, high-quality food. Researchers are constantly seeking new ways to protect foods from insect pests and fungi. This study used GC-IMS to analyze the volatile organic compounds and flavor characteristics of Finger Citron in response to different doses of 60Co irradiation. The principal component analysis method was used to explore the overall differences in flavor spectra, and a total of 60 compounds were identified. The fingerprints of volatile organic compounds in the samples showed that the volatile organic compounds with doses of 60Co irradiation in about 0 kGy and 5 kGy are similar, while the 10 kGy samples are quite different. The PCA results showed that the similarity between 0 kGy and 5 kGy was slightly higher, and the difference between 10 kGy and other samples was greater. Therefore, it was determined that 60Co irradiation with a 10 kGy intensity has a significant influence on the content of volatile oils components, while 60Co irradiation with a 5 kGy intensity has little effect. Irradiation technology is demonstrated as a promising method of food sterilization, but the irradiation dose and chemical composition must be taken into consideration.

Ecological Momentary Assessment and Machine Learning for Predicting Suicidal Ideation Among Sexual and Gender Minority Individuals.

Importance: Suicidality poses a serious global health concern, particularly in the sexual and gender minority population. While various studies have focused on investigating chronic stressors, the precise prediction effect of daily experiences on suicide ideation remains uncertain. Objective: To test the extent to which mood fluctuations and contextual stressful events experienced by sexual and gender minority individuals may predict later short- and long-term suicide ideation. Design, Setting, and Participants: This diagnostic study collected twice-daily data on mood states and stressful events from sexual and gender minority individuals over 25 days throughout 3 waves of the Chinese Lunar New Year (before, during, and after), and follow-up surveys assessing suicidal ideation were conducted 1, 3, and 8 months later. Online recruitment advertisements were used to recruit young adults throughout China. Eligible participants were self-identified as sexual and gender minority individuals aged 18 to 29 years. Those who were diagnosed with psychotic disorders (eg, schizophrenia spectrum or schizotypal disorder) or prevented from objective factors (ie, not having a phone or having an irregular sleep rhythm) were excluded. Data were collected from January to October 2022. Main Outcomes and Measures: To predict short-term (1 month) and longer-term (3 and 8 months) suicidal ideation, the study tested several approaches by using machine learning including chronic stress baseline data (baseline approach), dynamic patterns of mood states and stressful events (ecological momentary assessment [EMA] approach), and a combination of baseline data and dynamic patterns (EMA plus baseline approach). Results: A total of 103 sexual and gender minority individuals participated in the study (mean [SD] age, 24.2 [2.5] years; 72 [70%] female). Of these, 19 (18.4%; 95% CI, 10.9%-25.9%), 25 (24.8%; 95% CI, 16.4%-33.2%), 30 (29.4%; 95% CI, 20.6%-38.2%), and 32 (31.1%; 95% CI, 22.2%-40.0%) reported suicidal ideation at baseline, 1, 3, and 8 months follow-up, respectively. The EMA approach showed better performance than the baseline and baseline plus EMA approaches at 1-month follow-up (area under the receiver operating characteristic curve [AUC], 0.80; 95% CI, 0.78-0.81) and slightly better performance on the prediction of suicidal ideation at 3 and 8 months' follow-up. In addition, the best approach predicting suicidal ideation was obtained during Lunar New Year period at 1-month follow-up, which had a mean AUC of 0.77 (95% CI, 0.74-0.79) and better performance at 3 and 8 months' follow-up (AUC, 0.74; 95% CI, 0.72-0.76 and AUC, 0.72; 95% CI, 0.69-0.74, respectively). Conclusions and Relevance: The findings in this study emphasize the importance of contextual risk factors experienced by sexual and gender minority individuals at different stages. The use of machine learning may facilitate the identification of individuals who are at risk and aid in the development of personalized process-based early prevention programs to mitigate future suicide risk.

Influence of 60Co-γ Irradiation on the Components of Essential Oil of Curcuma.

The gas chromatography-ion mobility spectrometry (GC-IMS) method is a new technology for detecting volatile organic compounds. This study was carried out to evaluate the effects of volatile aroma compounds of Curcuma essential oils (EOs) after 60Co radiation by GC-IMS. Dosages of 0, 5, and 10 kGy of 60Co were used to analyze EOs of Curcuma after 60Co irradiation (named EZ-1, EZ-2, and EZ-3). The odor fingerprints of volatile organic compounds in different EOs of Curcuma samples were constructed by headspace solid-phase microextraction and GC-IMS after irradiation. The differences in odor fingerprints of EOs were compared by principal component analysis (PCA). A total of 92 compounds were detected and 65 compounds were identified, most of which were ketones, aldehydes, esters, and a small portion were furan compounds. It was found that the volatile matter content of 0 kGy and 5 kGy was closer, and the use of 10 kGy 60Co irradiation would have an unstable effect on the EOs. In summary, it is not advisable to use a higher dose when using 60Co irradiation for sterilization of Curcuma. Due to the small gradient of irradiation dose used in the experiment, the irradiation dose can be adjusted appropriately according to the required sterilization requirements during the production and storage process of Curcuma to obtain the best irradiation conditions. GC-IMS has the advantages of GC's high separation capability and IMS's fast response, high resolution, and high sensitivity, and the sample requires almost no pretreatment; it can be widely used in the analysis of traditional Chinese medicines containing volatile components. It is shown that irradiation technology has good application prospects in the sterilization of traditional Chinese medicines, but the changes in irradiation dose and chemical composition must be paid attention to.

Prevalence and genetic diversity of multidrug-resistant Salmonella Typhimurium monophasic variant in a swine farm from China.

Salmonella 4,[5],12:i:-, a monophasic variant of S. Typhimurium, has become a global serovar causing animal and human infections since its first emergence in the late 1980's. Several previous studies showed the increasing prevalence of S. 4,[5],12:i:- in China, most of which were from swine with multidrug resistance (MDR) profiles. However, the molecular characteristic and evolution of S. 4,[5],12:i:- in the same swine farm are still unknown. In this study, a total of 54 S. enterica strains were isolated from different fattening pigs aged 1, 3, and 6 months, most of which belonged to S. 4,[5],12:i:-. Whole-genome sequencing revealed that all 45 S. 4,[5],12:i:- strains belonged to ST34 and were further divided into two different ribosomal STs and nine different core-genome STs. Phylogenetic analysis of 286 S. 4,[5],12:i:- strains in China, including 241 from the EnteroBase Salmonella database, revealed the genetic diversity of S. 4,[5],12:i:- and indicated that S. 4,[5],12:i:- in this swine farm might have multiple origins. Three different IncHI2 plasmids carrying various resistance genes were characterized by nanopore sequencing and could be conjugated to Escherichia coli. The colistin resistance gene mcr-1 and ESBLs gene blaCTX - M-14 were co-located on the chromosome of one strain. The dynamic changes in antimicrobial resistance regions and transferability of IncHI2 plasmids, as well as the chromosomal location of resistance genes, facilitated the diversity of the antimicrobial resistance characteristics in S. 4,[5],12:i:-. Since the swine farm is regarded as the important reservoir of MDR S. 4,[5],12:i:-, the prevalence and evolution of S. 4,[5],12:i:- from swine farms to pig products and humans should be continually monitored.

Evaluation of 60Co Irradiation on Volatile Components of Turmeric (Curcumae Longae Rhizoma) Volatile Oil with GC-IMS.

60Co irradiation is an efficient and rapid sterilization method. The aim of this work is to determine the changes in essential-oil composition under different irradiation intensities of 60Co and to select an appropriate irradiation dose with GC-IMS. Dosages of 0, 5, and 10 kGy of 60Co were used to analyze turmeric (Curcumae Longae Rhizoma) volatile oil after 60Co irradiation (named JH-1, JH-2, and JH-3). The odor fingerprints of volatile organic compounds in different turmeric volatile oil samples were constructed by headspace solid-phase microextraction and gas chromatography-ion mobility spectrometry (GC-IMS) after irradiation. The differences in odor fingerprints of volatile organic compounds (VOCs) were compared by principal component analysis (PCA). The results showed that 97 volatile components were detected in the volatile oil of Curcuma longa, and 64 components were identified by database retrieval. With the change in irradiation intensity, the volatile compounds in the three turmeric volatile oil samples were similar, but the peak intensity was significantly different, which was attributed to the change in compound composition and content caused by different irradiation doses. In addition, the principal component analysis showed that JH-2 and JH-3 were relatively correlated, while JH-1 and JH-3 were far from each other. In general, different doses of 60Co irradiation can affect the content of volatile substances in turmeric volatile oil. With the increase in irradiation dose, the peak area decreased, and so the irradiation dose of 5 kGy/min was better. It is shown that irradiation technology has good application prospects in the sterilization of foods with volatile components. However, we must pay attention to the changes in radiation dose and chemical composition.

A pangenome reference of 36 Chinese populations.

Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference1. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.

The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair.

Bone regeneration is a comprehensive process that involves different stages, and various growth factors (GFs) play crucial roles in the entire process. GFs are currently widely used in clinical settings to promote bone repair; however, the direct application of GFs is often limited by their fast degradation and short local residual time. Additionally, GFs are expensive, and their use may carry risks of ectopic osteogenesis and potential tumor formation. Nanomaterials have recently shown great promise in delivering GFs for bone regeneration, as they can protect fragile GFs and control their release. Moreover, functional nanomaterials can directly activate endogenous GFs, modulating the regeneration process. This review provides a summary of the latest advances in using nanomaterials to deliver exogenous GFs and activate endogenous GFs to promote bone regeneration. We also discuss the potential for synergistic applications of nanomaterials and GFs in bone regeneration, along with the challenges and future directions that need to be addressed.

Late­onset white cord syndrome following anterior cervical discectomy and fusion: A case report.

White cord syndrome refers to an emerging neurological dysfunction occurring after spinal decompression surgery with hyperenhancing changes on T2-weighted magnetic resonance imaging (T2WI). The pathophysiological mechanism is hypothesized to be an ischemia-reperfusion injury following chronic ischemic spinal cord decompression. A 54-year-old man was admitted to Jinhua Municipal Central Hospital with complaints of numbness and weakness in the extremities and swelling in the neck. MRI showed degeneration and herniation of the C4-C7 intervertebral discs. The patient underwent anterior cervical corpectomy and fusion (ACCF). On the 7th postoperative day, the patient reappeared with weakness of the limbs. Physical examination revealed paralysis. Emergency MRI suggested T2 high signal myelopathy and emergency surgery was performed following the diagnosis of white cord syndrome. Following the operation, the patient's neurological system gradually improved. The motor ability and sensory function of the extremities recovered at 7-month follow-up. Spine surgeons should be aware of this serious complication. The present case serves to provide experience for clinical treatment and diagnosis and encourage research into its pathophysiology.

Analysis of Altered Brain Dynamics During Episodic Recall and Detection of Generalized Anxiety Disorder.

Numerous blood oxygenation level-dependent (BOLD) imaging studies have shown that generalized anxiety disorder (GAD) can lead to abnormal activation of specific brain regions in patients. However, these methods lack sufficient temporal resolution to explain the underlying brain dynamics of GAD. The electroencephalogram (EEG) microstate allows us to explore brain dynamics at the subsecond level. We performed microstate analysis and source localization on the EEG data of 15 GADs and 14 healthy controls (HCs). We found two kinds of noncanonical microstate topologies (MS-4 and MS-5) in the episodic recall tasks. Compared with HCs, the duration and coverage of MS-5 were significantly reduced in GADs and positively correlated with the GAD-7 scores. The results of source localization showed obvious activation in the prefrontal lobe, parietal lobe, temporal lobe, and fusiform gyri. Moreover, we propose an improved capsule network to capture EEG spatial features and combine them with temporal parameters of microstates for more reliable GAD detection. The sensor-level EEG data and the source-level EEG data obtained by source reconstruction are used as input to the model. The optimal configuration combined the spatial features of source-level data with microstate features and achieved the highest classification accuracy. Collectively, the statistical results indicated remarkable differences in dynamic brain parameters between the two groups, and patients with GAD may have abnormalities in their higher sensory cortex that affect the processing of anxiety signals. Furthermore, our proposed fusion framework provides a reliable method for GAD automatic detection.

Immobilization of Pb and Zn in Contaminated Soil Using Alumina-Silica Nano-Amendments Synthesized from Coal Fly Ash.

To apply coal fly ash to the remediation of heavy-metal-contaminated soil, an alumina-silica nano-amendment (ASNA) was synthesized from coal fly ash and was used for the immobilization of lead and zinc in contaminated soil. The investigation on the synthesis of the ASNA shows that the ASNA can be obtained under a roasting temperature of 700 °C, a ratio of alkali to coal fly ash of 1.2:1, and a molar ratio of silicon to aluminum of 1:1. The ASNA could increase the soil pH and cation exchange capacity (CEC) and decrease the bioavailability of Pb and Zn. When the ASNA addition increased from 0 to 2%, the bioavailability (extracted by CaCl2) of Pb and Zn decreased by 47% and 72%, respectively. Moreover, the addition of the ASNA facilitated the transformation of Pb from a reducible fraction to oxidizable and residual fractions and Zn from an exchangeable fraction to a residual fraction. The correlation analysis and cluster analysis verify that the ASNA modulates the chemical speciation of heavy metals by increasing the soil's CEC and pH, thereby immobilizing heavy metals. It is expected that this study can provide a new method for the remediation of Pb- and Zn-contaminated soil.

Florfenicol and oxazolidone resistance status in livestock farms revealed by short- and long-read metagenomic sequencing.

Antibiotic resistance genes (ARGs) as a novel type of environmental pollutant pose a health risk to humans. Oxazolidinones are one of the most important antibiotics for the treatment of Gram-positive bacterial infections in humans. Although oxazolidinones are not utilized in the livestock industry, florfenicol is commonly used on farms to treat bacterial infections, which may contribute to the spread of the cfr, optrA, and poxtA genes on farms. Using metagenomics sequencing, we looked into the antibiotic resistome context of florfenicol and oxazolidinone in 10 large-scale commercial farms in China. We identified 490 different resistance genes and 1,515 bacterial genera in the fecal samples obtained from 10 farms. Florfenicol-resistant Kurthia, Escherichia, and Proteus were widely present in these samples. The situation of florfenicol and oxazolidone resistance in pig farms is even more severe. The total number of genes and the abundance of drug resistance genes were higher in pigs than in chickens, including optrA and poxtA. All the samples we collected had a high abundance of fexA and floR. Through nanopore metagenomic analysis of the genetic environment, we found that plasmids, integrative and conjugative element (ICE), and transposons (Tn7-like and Tn558) may play an important role in the spread of floR, cfr, and optrA. Our findings suggest that florfenicol and oxazolidinone resistance genes have diverse genetic environments and are at risk of co-transmission with, for example, tetracycline and aminoglycoside resistance genes. The spread of florfenicol- and oxazolidinone-resistant bacteria on animal farms should be continuously monitored.