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Biomedical subjects

Juan Wang

Publications and source records attributed to Juan Wang.

6 recordsLinked to original sources

Genome-Wide Identification of the PAL Gene Family in Idesia polycarpa and Transcriptomic Responses to Botryosphaeria dothidea Infection.

Idesia polycarpa is a woody oil tree threatened by stem canker caused by Botryosphaeria dothidea, yet the organization and infection-responsive behavior of its phenylalanine ammonia-lyase (PAL) gene family remain poorly understood. Here, we identified five IpPAL genes and characterized their phylogenetic relationships, conserved features, duplication patterns, promoter cis-elements, and infection-associated expression profiles. Segmental and tandem duplication contributed to IpPAL family evolution, and all duplicated pairs showed Ka/Ks ratios below 1, consistent with purifying selection. RNA sequencing (RNA-seq) of contrasting Chengdu and Zhangjiajie provenances revealed distinct temporal responses. In Chengdu, IpPAL2-IpPAL4 were significantly upregulated at 24 h after inoculation, whereas all five genes were upregulated at 96 h. In Zhangjiajie, all five IpPAL genes were significantly upregulated at 24 h, while IpPAL2-IpPAL5 remained upregulated at 96 h. No IpPAL gene met the differential-expression criteria between provenances under mock conditions or at 24 h; at 96 h, IpPAL1 and IpPAL3 were lower and IpPAL5 was higher in Zhangjiajie than in Chengdu. Scanning electron microscopy (SEM) provided complementary qualitative evidence of provenance-associated tissue responses. These findings demonstrate time- and gene-specific IpPAL responses to B. dothidea and identify candidate genes for further functional analysis.

Ascomycota

Mendelian Randomization Analysis of NETs-Associated Inflammatory Traits and Type 2 Diabetes and its Complications.

Neutrophil extracellular traps (NETs) -associated inflammatory traits play a significant role in type 2 diabetes mellitus (T2DM) and its complications. Notably, IL-6, a key inflammatory cytokine, is intricately linked to the formation of NETs and the pathogenesis of T2DM and its complications. This study aimed to explore the causal association between NETs-associated inflammatory traits and T2DM, as well as its complications, using a Mendelian Randomization (MR) approach. This study utilized a two-sample MR design with data from Genome-Wide Association Studies (GWAS), comprising a large European population-based meta-analysis for T2DM and its complications. The primary method of analysis was the inverse variance weighted (IVW) approach, complemented by MR-Egger regression, weighted median, and weighted mode methods. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods to assess the robustness of the findings. The study indicated that genetically predicted levels of interleukin-6 (IL-6) were inversely associated with diabetic coronary artery disease (CAD) (OR = 0.8997, 95% CI: 0.8257-0.9803, P = 0.0158). Additionally, NETs showed significant associations with T2DM with renal complications (OR=0.97, 95% CI 0.9428-0.998, P = 0.0358) and T2DM with peripheral circulatory complications(OR = 1.0342, 95% CI 1.002-1.0673, P = 0.037). The significant IVW associations showed no evidence of heterogeneity or horizontal pleiotropy. This study suggests that genetically predicted NETs-associated inflammatory traits are associated with specific T2DM complications. Genetically predicted IL-6 was inversely associated with diabetic CAD, whereas NETs were associated with renal and peripheral circulatory complications in T2DM.

Diabetes Mellitus, Type 2

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to ≥8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n&#x2009;=&#x2009;73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5&#x2009;&#xb1;&#x2009;3.7 before treatment to 8.2&#x2009;&#xb1;&#x2009;4.1 after treatment (t&#x2009;=&#x2009;15.900, p&#x2009;<&#x2009;0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3&#x2009;&#xb1;&#x2009;2.9 before treatment to 8.0&#x2009;&#xb1;&#x2009;3.8 after treatment (t&#x2009;=&#x2009;17.232, p&#x2009;<&#x2009;0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7&#x2009;&#xb1;&#x2009;6.8 to 14.0&#x2009;&#xb1;&#x2009;5.0 (t&#x2009;=&#x2009;6.363, p&#x2009;<&#x2009;0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans

Reconstructing the 3D genome organization of Neanderthals reveals that chromatin folding shaped phenotypic and sequence divergence.

Changes in gene regulation were a major driver of the divergence of archaic hominins (AHs)-Neanderthals and Denisovans-and modern humans (MHs). The three-dimensional (3D) folding of the genome is critical for regulating gene expression; however, its role in recent human evolution has not been explored because the degradation of ancient samples does not permit experimental determination of AH 3D genome folding. To fill this gap, we apply novel deep learning methods for inferring 3D genome organization from DNA sequence to Neanderthal, Denisovan, and diverse MH genomes. Using the resulting 3D contact maps across the genome, we identify 167 distinct regions with diverged 3D genome organization between AHs and MHs. We show that these 3D-diverged loci are enriched for genes related to the function and morphology of the eye, supra-orbital ridges, hair, lungs, immune response, and cognition. Despite these specific diverged loci, the 3D genome of AHs and MHs is more similar than expected based on sequence divergence, suggesting that the pressure to maintain 3D genome organization constrained hominin sequence evolution. We also find that 3D genome organization constrained the landscape of AH ancestry in MHs today: regions more tolerant of 3D variation are enriched for introgression in modern Eurasians. Finally, we identify loci where modern Eurasians have inherited novel 3D genome folding patterns from AH ancestors and validate folding differences in a high-frequency locus using Hi-C, revealing a putative molecular mechanism for phenotypes associated with archaic introgression. In summary, our application of deep learning to predict archaic 3D genome organization illustrates the potential of inferring molecular phenotypes from ancient DNA to reveal previously unobservable biological differences.

Journal Article