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"Zeng, Xuan"
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A vaccine-based nanosystem for initiating innate immunity and improving tumor immunotherapy
The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for
Cd274
into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.
Immune checkpoint blockade (ICB) immunotherapy efficacy has still limitations. Here, the authors generate a vaccine that integrates CD274 siRNA into the L1 protein of human papillomavirus, which cooperates with ICB by activating innate immunity in breast cancer models.
Journal Article
Molecular dissection of rice phytohormone signaling involved in resistance to a piercing-sucking herbivore
• Phytohormone, particularly jasmonate (JA) and salicylate (SA) signaling, plays a central role in plant responses to herbivore and pathogen attack. Generally, SA mediates resistance responses against biotrophic pathogens and phloem-feeding insects, while JA mediates responses against necrotrophic pathogens and chewing insects. The phytohormonal responses mediating rice resistance to a piercing-sucking herbivore, the brown planthopper (BPH), remains unknown.
• Here, we combined transcriptome analysis, hormone measurements, genetic analysis and a field study to address this issue.
• Infestation by BPH adult females resulted in significant transcriptional reprograming. The upregulated genes were enriched in the JA signaling pathway. Consistently, the concentrations of JAs, but not SA, were dramatically increased in response to BPH attack. Two JA-deficient lines (AOC and MYC2 knockout) and two SA-deficient lines (nahG overexpression and NPR1 knockout) were constructed. BPH performed better on JA-deficient lines than on wild-type (WT) plants, but similarly on SA-deficient and WT plants. During BPH attack, the accumulation of defensive secondary metabolites was attenuated in JA-deficient lines compared with WT plants. Moreover, MYC2 mutants were more susceptible to planthoppers than WT plants in nature.
• This study reveals that JA signaling functions in rice defense against BPH.
Journal Article
The evolutionary dynamics of genome sizes and repetitive elements in Ensifera (Insecta: Orthoptera)
Background
In evolutionary biology, identifying and quantifying inter-lineage genome size variation and elucidating the underlying causes of that variation have long been goals. Repetitive elements (REs) have been proposed and confirmed as being among the most important contributors to genome size variation. However, the evolutionary implications of genome size variation and RE dynamics are not well understood.
Results
A total of 35 Ensifera insects were collected from different areas in China, including nine species of crickets and 26 species of katydids. The genome sizes of seven species were then determined using flow cytometry. The RepeatExplorer2 pipeline was employed to retrieve the repeated sequences for each species, based on low-coverage (0.1 X) high-throughput Illumina unassembled short reads. The genome sizes of the 35 Ensifera insects exhibited a considerable degree of variation, ranging from 1.00 to 18.34 pg. This variation was more than 18-fold. Similarly, the RE abundances exhibited considerable variation, ranging from 13.66 to 61.16%. In addition, the Tettigonioidea had larger genomes and contained significantly more REs than did the Grylloidea genomes. Analysis of the correlation between RE abundance and the genome size of 35 Ensifera insects revealed that the abundance of REs, transposable elements (TEs), long terminal repeats (LTRs), and long interspersed nuclear elements (LINEs) are significantly correlated with genome size. Notably, there is an inflection point in this correlation, where species with increasingly large genomes (e.g., > 5–10 pg) have repeats that contribute less to genome expansion than expected. Furthermore, this study revealed contrasting evolutionary directions between the Tettigonioidea and Grylloidea clades in terms of the expansion of REs. Tettigonioidea species exhibit a gradual increase in ancestral genome size and RE abundance as they diverge, while Grylloidea species experience sustained genome contraction.
Conclusions
This study reveals extensive variation in genome size and RE abundance in Ensifera insects, with distinct evolutionary patterns across two major groups, Tettigonioidea and Grylloidea. This provides valuable insights into the variation in genome size and RE abundance in Ensifera insects, offering a comprehensive understanding of their evolutionary history.
Journal Article
CRISPR/Cas9-mediated mutation of OsSWEET14 in rice cv. Zhonghua11 confers resistance to Xanthomonas oryzae pv. oryzae without yield penalty
Background
Bacterial blight of rice, caused by
Xanthomonas oryzae
pv.
oryzae
(
Xoo
), is a devastating rice disease in Southeast Asia and West Africa.
OsSWEET14
, encoding a sugar transporter, is known to be a major susceptible gene of bacterial blight targeted by four different transcription activator-like (TAL) effectors from either Asian or African
Xoo
strains. However, the
OsSWEET14
single knockout or promoter mutants in the Kitaake background are moderately resistant or even susceptible to African
Xoo
strains. Therefore, in this study, we knocked out
OsSWEET14
in rice cv. Zhonghua 11 background for disease assessment.
Results
In this study, CRISPR/Cas9 was utilized to disrupt the function of
OsSWEET14
by modifying its corresponding coding region in the genome of rice cv. Zhonghua 11 (
CR-S14
). In total, we obtained nine different
OsSWEET14
-mutant alleles. Besides conferring broad-spectrum resistance to Asian
Xoo
strains, tested mutant alleles also showed strong resistance to African
Xoo
strain AXO1947. Moreover, the expression of
OsSWEET14
was detected in vascular tissues, including the stem, leaf sheath, leaf blade and root. The disruption of
OsSWEET14
led to increased plant height without a reduction in yield.
Conclusions
Disruption of
OsSWEET14
in the Zhonghua 11 background is able to confer strong resistance to African
Xoo
strain AXO1947 and Asian
Xoo
strain PXO86.
CR-S14
has normal reproductive growth and enhanced plant height under normal growth conditions. These results imply that
CR-S14
may serve as a better tester line than
sweet14
single-knockout mutant in the Kitaake background for the diagnostic kit for rice blight resistance. The genetic background and increased plant height need to be taken into consideration when utilizing
OsSWEET14
for resistant rice breeding.
Journal Article
High-efficiency and stable short-delayed fluorescence emitters with hybrid long- and short-range charge-transfer excitations
The pursuit of ideal short-delayed thermally activated delayed fluorescence (TADF) emitters is hampered by the mutual exclusion of a small singlet-triplet energy gap (Δ
E
ST
) and a large oscillator strength (
f
). Here, by attaching an multiresonance-acceptor onto a sterically-uncrowded donor, we report TADF emitters bearing hybrid electronic excitations with a main donor-to-acceptor long-range (LR) and an auxiliary bridge-phenyl short-range (SR) charge-transfer characters, balancing a small Δ
E
ST
and a large
f
. Moreover, the incorporation of dual equivalent multiresonance-acceptors is found to double the
f
value without affecting the Δ
E
ST
. A large radiative decay rate over an order of magnitude higher than the intersystem crossing (ISC) rate, and a decent reverse ISC rate of >10
6
s
−1
are simultaneously obtained in one emitter, leading to a short delayed-lifetime of ~0.88 μs. The corresponding organic light-emitting diode exhibits a record-high maximum external quantum efficiency of 40.4% with alleviated efficiency roll-off and extended lifetime.
To possess a small singlet-triplet energy gap and a large oscillator strength simultaneously is critical for efficient thermally activated delayed fluorescent emitters. Here, the authors attach an multiresonance-acceptor onto a sterically-uncrowded donor for realizing a device efficiency of 40.4%.
Journal Article
Prevalence of Childhood Sexual Abuse Among Women Using the Childhood Trauma Questionnaire: A Worldwide Meta-Analysis
Childhood sexual abuse (CSA) is a common form of childhood maltreatment. Several studies have shown that CSA adversely affects the physical and mental health. Numerous studies have evaluated the prevalence of CSA among females using various instruments. In this meta-analysis, we estimated the rate of CSA among women using the short form of the Childhood Trauma Questionnaire for the first time. Four databases (PsycINFO, PubMed, Cochrane Library, and Embase) were systematically searched for studies published as of April 2, 2018. Forty-eight articles (53 groups of samples) covering 22,224 individuals, including women, from 16 countries were selected. Using the random-effects model, the pooled overall rate of CSA was 24% (95% confidence interval [21%, 27%]). On subgroup analyses, the rate of female CSA in people with mental illness was higher than that in the general group; this result showed variability among different geographical regions.
Journal Article
The effects of IL-1β stimulated human umbilical cord mesenchymal stem cells on polarization and apoptosis of macrophages in rheumatoid arthritis
Macrophages play an important role in the pathogenesis of rheumatoid arthritis (RA), in which the functions of pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2) are different. Our previous studies have demonstrated that interleukin-1β (IL-1β) stimulated human umbilical cord mesenchymal stem cells (hUCMSCs) increase the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and initiate breast cancer cell apoptosis via ligand to death receptor 4 (DR4) and DR5. In this study, we examined the effect of IL-1β stimulated hUCMSCs (IL-1β-hUCMSCs) on immunoregulation of M1 and M2 macrophages in vitro and in the RA mouse model. The results showed that IL-1β-hUCMSCs increased macrophage polarization into M2 macrophages and enhanced apoptosis of M1 macrophages in vitro. Moreover, the intravenous injected IL-1β-hUCMSCs in RA mice rehabilitated the imbalance of M1/M2 ratio and thus demonstrated the potential to reduce inflammation in RA. This study advances our knowledge of the underlying immunoregulatory mechanisms involved in IL-1β-hUCMSCs to induce M1 macrophage apoptosis and promote the anti-inflammatory polarization of M2 macrophages and demonstrates the potential of IL-1β-hUCMSCs to reduce inflammation in RA.
Journal Article
Novel APD Array Configurations for Improved Detection Area and Frequency Response
This paper presents two novel avalanche photodiode (APD) array structures designed to significantly enhance both detection area and bandwidth, overcoming the common trade-off between these parameters in conventional photodetectors. The impact of various parameters on the bandwidths of the two distinct array structures was theoretically simulated. Experimental validation using the self-fabricated 2 × 2 array on PCB board confirmed the bandwidth enhancement realized through inductor integration, with one APD array demonstrating an increase to 780 MHz (1.41 times greater) and another showing an increase to 1.21 GHz (1.35 times greater). Unlike prior works where array bandwidth is often lower than single detectors, our structures maintain high bandwidth while expanding the detection area. Structure 2 is particularly recommended over Structure 1 because of its lower noise, better signal-to-noise ratio (SNR), and reduced power consumption.
Journal Article
The Distinct Functions of Dopaminergic Receptors on Pain Modulation: A Narrative Review
Chronic pain is considered an economic burden on society as it often results in disability, job loss, and early retirement. Opioids are the most common analgesics prescribed for the management of moderate to severe pain. However, chronic exposure to these drugs can result in opioid tolerance and opioid-induced hyperalgesia. On pain modulation strategies, exploiting the multitarget drugs with the ability of the superadditive or synergistic interactions attracts more attention. In the present report, we have reviewed the analgesic effects of different dopamine receptors, particularly D1 and D2 receptors, in different regions of the central nervous system, including the spinal cord, striatum, nucleus accumbens (NAc), and periaqueductal gray (PAG). According to the evidence, these regions are not only involved in pain modulation but also express a high density of DA receptors. The findings can be categorized as follows: (1) D2-like receptors may exert a higher analgesic potency, but D1-like receptors act in different manners across several mechanisms in the mentioned regions; (2) in the spinal cord and striatum, antinociception of DA is mainly mediated by D2-like receptors, while in the NAc and PAG, both D1- and D2-like receptors are involved as analgesic targets; and (3) D2-like receptor agonists can act as adjuvants of μ-opioid receptor agonists to potentiate analgesic effects and provide a better approach to pain relief.
Journal Article