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Biology subjects

Li, Y.-T.

Publications and source records attributed to Li, Y.-T..

9 recordsLinked to original sources

The circ_0074371/miR-4738-3p/AMPK Signaling Axis Induces M1 Macrophage Polarization and Restricts Intracellular Survival of Mycobacterium tuberculosis

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, remains endemic in regions where it is prevalent. Mycobacterium tuberculosis is an intracellular pathogen that can survive within host macrophages; however, the mechanisms governing its long-term persistence and the progression to active pulmonary tuberculosis remain poorly understood. Circular RNAs (circRNAs) have been implicated in the initiation and progression of numerous diseases. In our previous study, circRNA sequencing identified several circRNAs associated with tuberculosis progression. In the present study, sequencing and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that Circ_0074371 was significantly downregulated in monocytes from patients with active pulmonary tuberculosis (ATB) and was closely associated with disease onset and progression, exhibiting considerable diagnostic value for ATB. Functional experiments further showed that Circ_0074371 significantly impaired the intracellular survival of Mtb and promoted M1 macrophage polarization. Mechanistically, Circ_0074371 acted as a competing endogenous RNA by sequestering miR-4738-3p, a potent negative regulator of AMP-activated protein kinase (AMPK) activation. Collectively, these findings identify Circ_0074371 as a tuberculosis-associated circRNA that regulates AMPK activity and reveal a novel mechanism through which Circ_0074371 influences macrophage polarization via the AMPK pathway, providing new insights into potential therapeutic targets for ATB.

immunology↗

X-ray irradiation hinders flight ability of Cydia pomonella male moths by energy metabolism dysfunction

Flight in insects is essential for behaviors such as courtship, foraging, and migration, with energy metabolism serving as its primary energy source. Previous study indicates that X-ray irradiation, even at optimized doses, compromises the flight capacity of male Cydia pomonella moths utilized in sterile insect technique (SIT) programs. However, the underlying mechanisms of this phenomenon have not been fully understood. In this study, we report that the disruption of energy metabolism processes contributing to the diminished flight capabilities observed in X-ray irradiated sterile C. pomonella moths. Compared to the non-irradiated group, irradiated moths exhibited significantly decreased adenosine triphosphate (ATP) levels. Furthermore, a reduction in the enzymatic activity of key components within carbon metabolism pathways was observed, including citrate synthase (CS) in the tricarboxylic acid cycle (TCA), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glycerol 3-phosphate dehydrogenase (GPDH) in glycolysis, and 3-Hydroxyl-CoA dehydrogenase (HOAD) in fatty acid metabolism. Transcriptional analysis revealed downregulation of expression of genes associated with energy metabolism in the primary locomotor tissues post-irradiation, specifically those encoding CS (CS2), GAPDH (Gapdh2), GPDH (GPD2), and HOAD (HADHA, HADH1, B0272, HADH2) enzymes. Additionally, exogenous supplementation with decanoic acid and citric acid, the agonist and product of CS respectively, enhanced the TCA cycle, increased energy production, and restored flight capacity in sterile moths. These findings not only confirm that X-ray irradiation disrupts energy metabolism leading to impaired flight, but also offer a potential strategy to overcome this limitation before releasing sterile moths as component of integrated pest management programme using the SIT. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/644052v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@c05e61org.highwire.dtl.DTLVardef@17461d9org.highwire.dtl.DTLVardef@1c41b70org.highwire.dtl.DTLVardef@1e58b48_HPS_FORMAT_FIGEXP M_FIG Graphic Abstract C_FIG

zoology↗

Different Roles of D1/D2 Medium Spiny Neurons in the Nucleus Accumbens in Pair Bond Formation of Male Mandarin Voles

The mesolimbic dopamine (DA) system has been implicated in pair bond formation. However, involvements of DA release, real time activities, and electrophysiological activities of D1/D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell in pair bonding remain unclear. This work verified that male mandarin voles after pair bonding released higher levels of DA in the NAc shell and displayed higher levels of D1 MSNs activity and lower levels of D2 MSNs activity upon sniffing their partners compared to upon sniffing an unknown female. Moreover, pair bonding induced differential alterations in both synaptic plasticity and neuronal intrinsic excitability in both D1 MSNs and D2 MSNs. In addition, chemogenetic inhibition of ventral pallidum (VP) -projecting D2 MSNs in the NAc shell enhanced pair bond formation, while chemogenetic activation of VP-projecting D2 MSNs in the NAc shell inhibited pair bond formation. These findings suggest that different neuronal activity of NAc shell D1 MSNs / D2 MSNs regulated by increasing DA release after pair bonding may be a neurobiological mechanism underlying pair bond formation.

neuroscience↗

Increasing the reliability of functional connectivity by predicting long-scan functional connectivity based on short-scan functional connectivity: model exploration, explanation, validation, and application.

Functional connectivity (FC) is a widely used imaging parameter of functional magnetic resonance imaging (fMRI). However, low reliability has been a concern among researchers, particularly in small-sample-size studies. Previous studies have shown that FC based on longer fMRI scans was more reliable, therefore, a feasible solution is to predict long-scan FCs using existing short-scan FCs. This study explored three different generalized linear models (GLMs) using the human connectome project (HCP) dataset. We found that the GLM based on individual short-scan FC could effectively predict long-scan individual FC value, while GLMs based on whole-brain FCs and dynamic FC performed better in predicting long-scan summed FC value of whole brain. The models were explained through visualization of weights in models. Besides, the differences in three GLMs could be explained as differences in distribution features of FC matrices predicted by them. Results were validated in different datasets, including the Consortium for Reliability and Reproducibility (CoRR) project and our local dataset. These models could be applied to improve the test-retest reliability of FC and to improve the performance of connectome-based predictive models (CPM). In conclusion, we developed three GLMs that could be used to predict long-scan FC from short-scan FC, and these models were robust across different datasets and could be applied to improve the test-retest reliability of FC and the performance of CPM.

neuroscience↗

Transcription factor AhR regulates glutathione S-transferases (GSTs) conferring resistance to lambda-cyhalothrin in Cydia pomonella

Transcription factor aryl hydrocarbon receptor (AhR) can enhance insect resistance to insecticides by regulating the detoxification metabolic network. Our previous studies have confirmed that overexpression of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are both involved in lambda-cyhalothrin resistance in Cydia pomonella. In this study, we report that AhR regulates GSTs thus conferring lambda-cyhalothrin resistance in C. pomonella. Spatiotemporal expression patterns indicated that AhR gene of C. pomonella (CpAhR) was highly expressed in the Malpighian tubules of larvae. Moreover, the expression of CpAhR was induced by lambda-cyhalothrin exposure and was up-regulated in a lambda-cyhalothrin-resistant population. RNA interference (RNAi) of the expression of CpAhR could effectively decrease the relative expression level of CpGSTe3 and enzyme activity of GSTs, but not P450s, further reducing the tolerance of larvae to lambda-cyhalothrin. Furthermore, {beta}-naphthoflavone (BNF), a novel agonist of AhR, can effectively increase the expression of CpAhR and the activity of the GSTs enzyme, resulting in the enhancement of larvae tolerance to lambda-cyhalothrin. These results demonstrate that lambda-cyhalothrin exposure can effectively activate the expression of CpAhR and increase GSTs enzyme thus leading to the development of resistance to lambda-cyhalothrin, which enriches the theory of insecticide resistance regulation in C. pomonella.

molecular biology↗

Dorsal raphe nuclei to anterior cingulate cortex 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability in mandarin voles

Consolation is a common response to the distress of others in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. By using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nucleus (DR) or optogenetic inhibition of 5-HT terminals in the anterior cingulate cortex (ACC) significantly decreased allogrooming time in the consolation test and reduced sociability in the three-chamber test. The release of 5-HT within the ACC and the activity of DR neurons were significantly increased during allogrooming, sniffing and social approaching. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided first direct evidence that DR-ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability.

neuroscience↗

Identifications of novel avian and mammalian deltaviruses filled the large evolutionally gaps and revealed inter-family transmission of deltaviruses

Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite-helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.

microbiology↗

Defective photosynthetic adaptation mechanism in winter restricts the introduction of overwintering plant to high latitudes

Because of the need for agriculture and landscaping, many overwintering evergreen and biennial species that maintain green leaves over winter were introduced to higher latitudes. The green leaves of introduced overwintering species have to withstand a harsher winter, especially lower temperature, than in their native region of origin. Although the responses and adaptability of photosynthetic apparatus to winter conditions in native overwintering species were widely studied, the experimental results on the introduced overwintering species are very limited. Here, the photosynthetic adaptability during winter was analyzed in two native overwintering species, pine (woody plants), winter wheat (herb), and two introduced overwintering species, bamboo (woody plants), lilyturf (herb). The native species exhibited higher capacity for photosynthetic CO2 fixation and lower susceptibility for photoinhibition than introduced species during winter. Photosynthesis related proteins, such as PsbA, PsaA, Rubisco and Lhcb1, were marginally affected in native species, but significantly degraded in introduced species during winter. More interestingly, the PSII photoinhibition was mainly caused by up-regulation of photoprotection mechanism, non-photochemical quenching, in native species, but by photodamage in introduced species. This study indicates that the growth and survival of introduced overwintering species is limited by their photosynthetic adaptability to the harsher winter conditions at high latitudes.

plant biology↗

Inhibitor of the spindle assembly checkpoint surpasses apoptosis sensitizer in synergy with taxanes

The antitumor effect of taxanes have been attributed to their ability to induce mitotic arrest through activation of the spindle assembly checkpoint. Cell death following prolonged mitotic arrest is mediated by the intrinsic apoptosis pathway. Thus, apoptosis sensitizers which inhibit antiapoptotic Bcl-2 family proteins has been shown to enhance taxanes-induced cell death. By contrast, spindle checkpoint disruption facilitates mitotic slippage and is thought to promote taxanes resistance. Notably, other modes of cell death also contribute to treatment outcomes. Here we show that inhibition of the spindle checkpoint suppresses taxanes induced apoptosis but increases terminal growth arrest of tumor cells with features of cellular senescence. By using clonogenic assay which measures the net result of multiple forms of cell death and is more reflective of therapeutic response, our finding suggests apoptosis is not a major determinant of antitumor efficacy of taxanes, whereas spindle checkpoint inhibitor displays a long-term advantage over apoptosis sensitizer in blocking colony outgrowth of tumor cells when combined with different microtubule toxins, therefore represents a superior therapeutic strategy.\n\nSIGNIFICANCEApoptosis has long been regarded as the primary mechanism of anti-cancer efficacy of taxanes, while the role of the spindle assembly checkpoint (SAC) in treatment response to taxanes has been controversial. Either apoptosis sensitizer or inhibitor of SAC has been reported to synergize with taxanes. While inhibitor of antiapoptotic proteins potentiates taxanes induced apoptosis, inhibitor of SAC suppresses apoptosis by facilitating mitotic slippage, that is why it is implicated in taxanes resistance. By demonstrating that apoptotic rates are not associate with long-term treatment response, not only do we find that inhibitor of SAC displays a long-term advantage over apoptosis sensitizer in combination with taxanes, but we also resolve the dispute around the role of SAC in cellular response to taxanes.

cancer biology↗