Two-Sex Life Table Analysis for Optimizing Beauveria bassiana Application against Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae).

Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) is a highly dispersive, polyphagous insect pest that severely defoliates crops. Excessive reliance on synthetic insecticides leads to ecological pollution and resistance development, urging scientists to probe eco-friendly biopesticides. Here, we explore the virulence of an entomopathogenic fungus, Beauveria bassiana, against S. exigua, resulting in 88% larval mortality. Using an age-stage, two-sex life table, we evaluated the lethal and sublethal effects of B. bassiana on the demographic parameters of S. exigua, including survival, development, and reproduction. Sublethal (LC20) and lethal concentrations (LC50) of B. bassiana impacted the parental generation (F0), with these effects further influencing the demographic parameters of the first filial generation (F1). The infected F1 offsprings showed a reduced intrinsic rate of increase (r), mean generation time (T), and net reproduction rate (R0). Larval developmental duration varied significantly between the control (10.98 d) and treated groups (LC20: 10.42; LC50: 9.37 d). Adults in the treated groups had significantly reduced lifespans (M: 8.22; F: 7.32 d) than the control (M: 10.00; F: 8.22 d). Reduced fecundity was observed in the B. bassiana-infected groups (LC20: 313.45; LC50: 223.92 eggs/female) compared to the control (359.55 eggs/female). A biochemical assay revealed elevated levels of detoxification enzymes (esterases, glutathione S-transferases, and acetylcholinesterase) in the F0 generation after B. bassiana infection. However, the enzymatic activity remained non-significant in the F1 generation likely due to the lack of direct fungal exposure. Our findings highlight the enduring effects of B. bassiana on the biological parameters and population dynamics of S. exigua, stressing its use in eco-friendly management programs.

Research progress on sexual functioning and associated factors in childhood cancer survivors: a scoping review.

Background: Childhood Cancer Survivors (CCSs) are more likely to report sexual dysfunction than people without cancer history. Sexual functioning encompasses more than just sexual dysfunction. The scarcity of information regarding the status and influencing factors of sexual functioning in CCSs, hampers to devise suitable screening or interventions. This review aims to summarize research progress on sexual functioning and associated factors among CCSs. Methods: This review protocol is registered in PROSPERO(CRD42023427939) and performed according to PRISMA guidelines. From inception to November 15, 2023, a comprehensive search was conducted in PubMed, EMBASE, CINAHL, Web of Science, SCOPUS, PsycINFO, CNKI Database, Wanfang of Chinese Database, SinoMed Database and Cochrane Library on sexual functioning and childhood cancer survivors. Inclusion criteria were English or Chinese studies focusing on sexual functioning and related factors of cancer survivors, who diagnosed with cancer before 18 years old, and were adult and disease-free when participating in the study. Studies were excluded if the focus was on adult cancer patients or without age information. Findings: 395 records were retrieved, and 22 studies were finally included in this review. Results suggest that CCSs experience a substantial burden of sexual issues, including delayed psychosexual development, low satisfaction, and high prevalence of dysfunction. Underlying factors related to sexual functioning of CCSs were identified, including demographic, cancer treatment-related, psychological, and physiological factors. The historical change in research on sexual functioning was summarized. Interpretation: Research on sexual functioning among CCSs is limited. The extent to which cancer and related treatments affect sexual functioning remains largely unknown. The relationships between various factors and mechanisms underlying sexual functioning need to be confirmed by more rigorous studies to enable effective interventions to be developed. Funding: None.

Ultrasound-Activatable In Situ Vaccine for Enhanced Antigen Self- and Cross-Presentation to Overcome Cancer Immunotherapy Resistance.

Insufficient antigen self-presentation of tumor cells and ineffective antigen cross-presentation by dendritic cells (DCs) contribute to diminished immune recognition and activation, which cause resistance to immunotherapies. Herein, we present an ultrasound-activatable in situ vaccine by utilizing a hybrid nanovesicle composed of a thylakoid (TK)/platelet (PLT) membrane and a liposome encapsulating DNA methyltransferase inhibitor zebularine (Zeb) and sonosensitizer hematoporphyrin monomethyl ether (HMME). Upon local exposure to ultrasound, reactive oxygen species (ROS) are generated and induce the sequential release of the payloads. Zeb can efficiently inhibit tumor DNA hypermethylation, promoting major histocompatibility complex class I (MHC-I) molecules-mediated antigen self-presentation to improve immune recognition. Meanwhile, the catalase on the TK membrane can decompose the tumoral overexpressed H2O2 into O2, which boosts the generation of ROS and the destruction of tumor cells, resulting in the in situ antigen release and cross-presentation of tumor antigens by DCs. This in situ vaccine simultaneously promotes antigen self-presentation and cross-presentation, resulting in heightened antitumor immunity to overcome resistance.

Construction and Application of a PD-L1-Targeted Multimodal Diagnostic and Dual-Functional Theranostics Nanoprobe.

Background: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target. Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67±3.45 for PET and 6.63±0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups. Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT.

A Clinical Study on Chinese Five-Element Music Therapy Combined with Auricular-Plaster Therapy in Treating Perimenopausal Insomnia and Anxiety.

Objective: To evaluate the clinical effects of five-element music therapy combined with auricular-plaster therapy for perimenopausal insomnia with anxiety. This study aimed to leverage the complementary effects of both approaches to provide patients with a more comprehensive and personalized therapeutic experience. Methods: In this experiment, 90 cases of perimenopausal insomnia patients were selected and randomly assigned to the treatment group (45 cases) and the control group (45 cases) using the random number table method. In the treatment group, except for 2 cases who withdrew, the remaining 43 cases were observed and treated with Five Elements Music combined with auricular acupressure therapy. In the control group, except 3 cases withdrew, 42 cases were observed and given alprazolam oral treatment. The treatment course of both groups was 4 weeks. Data such as Pittsburgh Sleep Quality Index (PSQI) and Hamilton Anxiety Scale (HAMA) scores were also recorded for all patients before and after treatment. Results: After treatment, the total effective rate was 93.02% in the treatment group and 88.10% in the control group. The PSQI and HAMA scores of the two groups after treatment improved compared to before treatment(P < .01). The curative effect in the treatment group was superior to that in the control group in terms of sleep quality and anxiety. Conclusion: The five-element music therapy combined with auricular-plaster therapy is effective in the treatment of perimenopausal insomnia with anxiety. Compared with traditional therapy, Chinese medicine non-drug therapy has the characteristics of green safety, simple effect, and low cost. It can avoid adverse reactions caused by long-term use of drugs, so It is a safe and reliable method, worthy of recommendation for clinical use.

A CAIX Dual-Targeting Small-Molecule Probe for Noninvasive Imaging of ccRCC.

Carbonic anhydrase IX (CAIX), a zinc metal transmembrane protein, is highly expressed in 95% of clear cell renal cell carcinomas (ccRCCs). A positron emission tomography (PET) probe designed to target CAIX in nuclear medicine imaging technology can achieve precise positioning, is noninvasive, and can be used to monitor CAIX expression in lesions in real time. In this study, we constructed a novel acetazolamide dual-targeted small-molecule probe [68Ga]Ga-LF-4, which targets CAIX by binding to a specific amino acid sequence. After attenuation correction, the radiolabeling yield reached 66.95 ± 0.57% (n = 5) after 15 min of reaction and the radiochemical purity reached 99% (n = 5). [68Ga]Ga-LF-4 has good in vitro and in vivo stability, and in vivo safety and high affinity for CAIX, with a Kd value of 6.62 nM. Moreover, [68Ga]Ga-LF-4 could be quickly cleared from the blood in vivo. The biodistribution study revealed that the [68Ga]Ga-LF-4 signal was concentrated in the heart, lung, and kidney after administration, which was the same as that observed in the micro-PET/CT study. In a ccRCC patient-derived xenograft (PDX) model, the signal significantly accumulated in the tumor after administration, where it was retained for up to 4 h. After competitive blockade with LF-4, uptake at the tumor site was significantly reduced. The SUVmax of the probe [68Ga]Ga-LF-4 at the ccRCC tumor site was three times greater than that in the PC3 group with low CAIX expression at 30 min (ccRCC vs PC3:1.86 ± 0.03 vs 0.62 ± 0.01, t = 48.2, P < 0.0001). These results indicate that [68Ga]Ga-LF-4 is a novel small-molecule probe that targets CAIX and can be used to image localized and metastatic ccRCC lesions.

Differences in Vaccination Consultation Preferred by Primary Health Care Workers and Residents in Community Settings.

OBJECTIVE: To evaluate the preference of primary HCWs and residents on vaccination consultation in community health services to provide evidence for vaccine hesitancy intervention strategies. METHODS: A discrete choice model (DCM) was constructed to evaluate the preference difference between primary HCWs and residents on vaccination consultation in community health services in China during May-July 2022. RESULTS: A total of 282 residents and 204 HCWs were enrolled in this study. The residents preferred consulting with an HCW-led approach (ß = 2.168), with specialized content (ß = 0.954), and accompanied by telephone follow-up (ß = 1.552). In contrast, the HCWs preferred face-to-face consultation (ß = 0.540) with an HCW-led approach (ß = 0.458) and specialized content (ß = 0.409), accompanied by telephone follow-up (ß = 0.831). College residents and residents with underlying self-reported disease may be near-critically inclined to choose traditional consultation (an offline, face-to-face consultation with standardized content and more prolonged duration) rather than a new-media consulting group (an online consultation with specialized content within 5 min). Urban HCWs preferred long-term consultation groups (the resident-led offline consultation with follow-up lasting more than 5 min). In contrast, rural HCWs preferred efficient consultation (the HCW-led, short-duration, standardized offline consultation mode). CONCLUSION: The selection preference for vaccine consultation reveals a gap between providers and demanders, with different groups exhibiting distinct preferences. Identifying these targeted gaps can help design more acceptable and efficient interventions, increasing their likelihood of success and leading to better resource allocation for policymakers to develop targeted vaccination policies.

BRD4 promotes gouty arthritis through MDM2-mediated PPARγ degradation and pyroptosis.

BACKGROUND: Gouty arthritis (GA) is characterized by monosodium urate (MSU) crystal accumulation that instigates NLRP3-mediated pyroptosis; however, the underlying regulatory mechanisms have yet to be fully elucidated. The present research endeavors to elucidate the regulatory mechanisms underpinning this MSU-induced pyroptotic cascade in GA. METHODS: J774 cells were exposed to lipopolysaccharide and MSU crystals to establish in vitro GA models, whereas C57BL/6 J male mice received MSU crystal injections to mimic in vivo GA conditions. Gene and protein expression levels were evaluated using real-time quantitative PCR, Western blotting, and immunohistochemical assays. Inflammatory markers were quantified via enzyme-linked immunosorbent assays. Pyroptosis was evaluated using immunofluorescence staining for caspase-1 and flow cytometry with caspase-1/propidium iodide staining. The interaction between MDM2 and PPARγ was analyzed through co-immunoprecipitation assays, whereas the interaction between BRD4 and the MDM2 promoter was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Mouse joint tissues were histopathologically evaluated using hematoxylin and eosin staining. RESULTS: In GA, PPARγ was downregulated, whereas its overexpression mitigated NLRP3 inflammasome activation and pyroptosis. MDM2, which was upregulated in GA, destabilized PPARγ through the ubiquitin-proteasome degradation pathway, whereas its silencing attenuated NLRP3 activation by elevating PPARγ levels. Concurrently, BRD4 was elevated in GA and exacerbated NLRP3 activation and pyroptosis by transcriptionally upregulating MDM2, thereby promoting PPARγ degradation. In vivo experiments showed that BRD4 silencing ameliorated GA through this MDM2-PPARγ-pyroptosis axis. CONCLUSION: BRD4 promotes inflammation and pyroptosis in GA through MDM2-mediated PPARγ degradation, underscoring the therapeutic potential of targeting this pathway in GA management.

Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål).

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

KRAS Mutation Detection with (2S,4R)-4-[18F]FGln for Noninvasive PDAC Diagnosis.

Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis and nonspecific symptoms and progresses rapidly, is the most common pancreatic cancer type. Inhibitors targeting KRAS G12D and G12C mutations have been pivotal in PDAC treatment. Cancer cells with different KRAS mutations exhibit various degrees of glutamine dependency; in particular, cells with KRAS G12D mutations exhibit increased glutamine uptake. (2S,4R)-4-[18F]FGln has recently been developed for clinical cancer diagnosis and tumor cell metabolism analysis. Thus, we verified the heterogeneity of glutamine dependency in PDAC models with different KRAS mutations by a visual and noninvasive method with (2S,4R)-4-[18F]FGln. Two tumor-bearing mouse models (bearing the KRAS G12D or G12C mutation) were injected with (2S,4R)-4-[18F]FGln, and positron emission tomography (PET) imaging features and biodistribution were observed and analyzed. The SUVmax in the regions of interest (ROI) was significantly higher in PANC-1 (G12D) tumors than in MIA PaCa-2 (G12C) tumors. Biodistribution analysis revealed higher tumor accumulation of (2S,4R)-4-[18F]FGln and other metrics, such as T/M and T/B, in the PANC-1 mouse models compared to those in the MIAPaCa-2 mouse models. In conclusion, PDAC cells with the KRAS G12D and G12C mutations exhibit various degrees of (2S,4R)-4-[18F]FGln uptake, indicating that (2S,4R)-4-[18F]FGln might be applied to detect KRAS G12C and G12D mutations and provide treatment guidance.

Activating astrocytic α2A adrenoceptors in hippocampus reduces glutamate toxicity to attenuate sepsis-associated encephalopathy in mice.

BACKGROUND: Glutamate metabolism disorder is an important mechanism of sepsis-associated encephalopathy (SAE). Astrocytes regulate glutamate metabolism. In septic mice, α2A adrenoceptor (α2A-AR) activation in the central nervous system provides neuroprotection. α2A-ARs are expressed abundantly in hippocampal astrocytes. This study was performed to determine whether hippocampal astrocytic α2A-AR activation confers neuroprotection against SAE and whether this protective effect is astrocyte specific and achieved by the modulation of glutamate metabolism. METHODS: Male C57BL/6 mice with and without α2A-AR knockdown were subjected to cecal ligation and puncture (CLP). They were treated with intrahippocampal guanfacine (an α2A-AR agonist) or intraperitoneal dexmedetomidine in the presence or absence of dihydrokainic acid [DHK; a glutamate transporter 1 (GLT-1) antagonist] and/or UCPH-101 [a glutamate/aspartate transporter (GLAST) antagonist]. Hippocampal tissue was collected for the measurement of astrocyte reactivity, GLT-1 and GLAST expression, and glutamate receptor subunit 2B (GluN2B) phosphorylation. In vivo real-time extracellular glutamate concentrations in the hippocampus were measured by ultra-performance liquid chromatography tandem mass spectrometry combined with microdialysis, and in vivo real-time hippocampal glutamatergic neuron excitability was assessed by calcium imaging. The mice were subjected to the Barnes maze and fear conditioning tests to assess their learning and memory. Golgi staining was performed to assess changes in the hippocampal synaptic structure. In vitro, primary astrocytes with and without α2A-AR knockdown were stimulated with lipopolysaccharide (LPS) and treated with guanfacine or dexmedetomidine in the presence or absence of 8-bromo- cyclic adenosine monophosphate (8-Br-cAMP, a cAMP analog). LPS-treated primary and BV2 microglia were also treated with guanfacine or dexmedetomidine. Astrocyte reactivity, PKA catalytic subunit, GLT-1 an GLAST expression were determined in primary astrocytes. Interleukin-1ß, interleukin-6 and tumor necrosis factor-alpha in the medium of microglia culture were measured. RESULTS: CLP induced synaptic injury, impaired neurocognitive function, increased astrocyte reactivity and reduced GLT-1 and GLAST expression in the hippocampus of mice. The extracellular glutamate concentration, phosphorylation of GluN2B at Tyr-1472 and glutamatergic neuron excitability in the hippocampus were increased in the hippocampus of septic mice. Intraperitoneal dexmedetomidine or intrahippocampal guanfacine administration attenuated these effects. Hippocampal astrocytes expressed abundant α2A-ARs; expression was also detected in neurons but not microglia. Specific knockdown of α2A-ARs in hippocampal astrocytes and simultaneous intrahippocampal DHK and UCPH-101 administration blocked the neuroprotective effects of dexmedetomidine and guanfacine. Intrahippocampal administration of DHK or UCPH-101 alone had no such effect. In vitro, guanfacine or dexmedetomidine inhibited astrocyte reactivity, reduced PKA catalytic subunit expression, and increased GLT-1 and GLAST expression in primary astrocytes but not in primary astrocytes that received α2A-AR knockdown or were treated with 8-Br-cAMP. Guanfacine or dexmedetomidine inhibited microglial reactivity in BV2 but not primary microglia. CONCLUSIONS: Our results suggest that neurocognitive protection against SAE after hippocampal α2A-AR activation is astrocyte specific. This protection may involve the inhibition of astrocyte reactivity and alleviation of glutamate neurotoxicity, thereby reducing synaptic injury. The cAMP/protein kinase A (PKA) signaling pathway is a potential cellular mechanism by which activating α2A-AR modulates astrocytic function.

Maintaining Toll signaling in Drosophila brain is required to sustain autophagy for dopamine neuron survival.

Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.

MiR-2b-3p Downregulated PxTrypsin-9 Expression in the Larval Midgut to Decrease Cry1Ac Susceptibility of the Diamondback Moth, Plutella xylostella (L.).

Crystal (Cry) toxins, produced by Bacillus thuringiensis, are widely used as effective biological pesticides in agricultural production. However, insects always quickly evolve adaptations against Cry toxins within a few generations. In this study, we focused on the Cry1Ac protoxin activated by protease. Our results identified PxTrypsin-9 as a trypsin gene that plays a key role in Cry1Ac virulence in Plutella xylostella larvae. In addition, P. xylostella miR-2b-3p, a member of the micoRNA-2 (miR-2) family, was significantly upregulated by Cry1Ac protoxin and targeted to PxTrypsin-9 downregulated its expression. The mRNA level of PxTrypsin-9, regulated by miR-2b-3p, revealed an increased tolerance of P. xylostella larvae to Cry1Ac at the post-transcriptional level. Considering that miR-2b and trypsin genes are widely distributed in various pest species, our study provides the basis for further investigation of the roles of miRNAs in the regulation of the resistance to Cry1Ac and other insecticides.

MicroRNA Targets PAP1 to Mediate Melanization in Plutella xylostella (Linnaeus) Infected by Metarhizium anisopliae.

MicroRNAs (miRNAs) play a pivotal role in important biological processes by regulating post-transcriptional gene expression and exhibit differential expression patterns during development, immune responses, and stress challenges. The diamondback moth causes significant economic damage to crops worldwide. Despite substantial advancements in understanding the molecular biology of this pest, our knowledge regarding the role of miRNAs in regulating key immunity-related genes remains limited. In this study, we leveraged whole transcriptome resequencing data from Plutella xylostella infected with Metarhizium anisopliae to identify specific miRNAs targeting the prophenoloxidase-activating protease1 (PAP1) gene and regulate phenoloxidase (PO) cascade during melanization. Seven miRNAs (pxy-miR-375-5p, pxy-miR-4448-3p, pxy-miR-279a-3p, pxy-miR-3286-3p, pxy-miR-965-5p, pxy-miR-8799-3p, and pxy-miR-14b-5p) were screened. Luciferase reporter assays confirmed that pxy-miR-279a-3p binds to the open reading frame (ORF) and pxy-miR-965-5p to the 3' untranslated region (3' UTR) of PAP1. Our experiments demonstrated that a pxy-miR-965-5p mimic significantly reduced PAP1 expression in P. xylostella larvae, suppressed PO activity, and increased larval mortality rate. Conversely, the injection of pxy-miR-965-5p inhibitor could increase PAP1 expression and PO activity while decreasing larval mortality rate. Furthermore, we identified four LncRNAs (MSTRG.32910.1, MSTRG.7100.1, MSTRG.6802.1, and MSTRG.22113.1) that potentially interact with pxy-miR-965-5p. Interference assays using antisense oligonucleotides (ASOs) revealed that silencing MSTRG.7100.1 and MSTRG.22113.1 increased the expression of pxy-miR-965-5p. These findings shed light on the potential role of pxy-miR-965-5p in the immune response of P. xylostella to M. anisopliae infection and provide a theoretical basis for biological control strategies targeting the immune system of this pest.

The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice.

BACKGROUND: Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown. METHODS: Here, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms. RESULTS: A total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression. CONCLUSIONS: Our study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.

MicroRNA-Mediated Host Immune Genes Manipulation Benefits AcMNPV Proliferation in Spodoptera frugiperda.

Spodoptera frugiperda is a highly destructive migratory pest that threatens various crops globally. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an effective biocontrol agent against lepidopteran pests. Here, we explored the molecular mechanisms underlying the immune response to AcMNPV infection in S. frugiperda. RNA-seq and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses identified the Toll, IMD, and apoptosis pathways as primary immune responses. Investigation into AcMNPV-induced apoptosis in the S. frugiperda cell line (Sf9) revealed that the Toll pathway activated the JNK via the TRAF6 (TNF receptor-associated factor 6) adapter. In addition, AcMNPV-induced the differential expression of several host-encoded microRNAs (miRNAs), with significant negative regulatory effects, on S. frugiperda antiviral immune genes. RNAi and miRNA-mimic mediated silencing of these genes resulted in increased AcMNPV proliferation. Our findings reinforce the potential of AcMNPV as a potent biocontrol agent and further our understanding of developing biotechnology-based targeted pest control agents.

Systematic identification of reference genes for qRT-PCR of Ardisia kteniophylla A. DC under different experimental conditions and for anthocyanin-related genes studies.

Ardisia kteniophylla A. DC, widely known as folk medicinal herb and ornamental plant, has been extensively investigated due to its unique leaf color, anti-cancer and other pharmacological activities. The quantitative real-time PCR (qRT-PCR) was an excellent tool for the analysis of gene expression with its high sensitivity and quantitative properties. Normalizing gene expression with stable reference genes was essential for qRT-PCR accuracy. In addition, no studies have yet been performed on the selection, verification and stability of internal reference genes suitable for A. kteniophylla, which has greatly hindered the biomolecular researches of this species. In this study, 29 candidate genes were successfully screened according to stable expression patterns of large-scale RNA seq data that from a variety of tissues and the roots of different growth stages in A. kteniophylla. The candidates were then further determined via qRT-PCR in various experimental samples, including MeJA, ABA, SA, NaCl, CuSO4, AgNO3, MnSO4, CoCl2, drought, low temperature, heat, waterlogging, wounding and oxidative stress. To assess the stability of the candidates, five commonly used strategies were employed: delta-CT, geNorm, BestKeeper, NormFinder, and the comprehensive tool RefFinder. In summary, UBC2 and UBA1 were found to be effective in accurately normalizing target gene expression in A. kteniophella regardless of experimental conditions, while PP2A-2 had the lowest stability. Additionally, to verify the reliability of the recommended reference genes under different colored leaf samples, we examined the expression patterns of six genes associated with anthocyanin synthesis and regulation. Our findings suggested that PAP1 and ANS3 may be involved in leaf color change in A. kteniphella. This study successfully identified the ideal reference gene for qRT-PCR analysis in A. kteniphella, providing a foundation for future research on gene function, particularly in the biosynthesis of anthocyanins.

Design and evaluation of blended teaching in the smart classroom combined with virtual simulation training in basic nursing courses.

OBJECTIVE: This study explored the application effect of smart classrooms combined with virtual simulation training in basic nursing courses for nursing undergraduates. METHODS: In this quasi-experimental study, a total of 135 undergraduate nursing students in the 2021 matriculating cohort were selected as the research subjects. The experimental group of Class 1 had 71 students, and a blended teaching design utilizing a smart classroom and virtual simulation training was adopted. The control group of Class 2 had 64 students, and traditional lecture-based teaching design was adopted. After the course, the independent learning ability scale, test scores and teaching effectiveness questionnaire were used to evaluate the teaching effect. All tests had a maximum score of 100. RESULTS: Nursing undergraduates in the experimental group had scores of 86.32 ± 8.25 for virtual simulation training and 84.82 ± 9.04 for peer-assisted learning. The scores of the theoretical examination, experimental examination, and subjective questions in the experimental group were significantly higher than those in the control group (P < 0.05). The approval rate of nursing undergraduates in the experimental group was significantly higher than that of the control group for four items (Ps < 0.05). Among the 71 students, most students (91.55%) claimed that the use of instructional designs increased the fun of the classroom. In addition to the dimension of information literacy, the total score of independent learning ability and the other three dimensions of the experimental group were significantly higher than those of the control group (P < 0.05). CONCLUSION: The teaching design combining smart classrooms and virtual simulation training can be applied to realize online blended teaching and classroom informatization, improving the academic performance and independent learning ability of nursing undergraduates, and thus achieving good teaching effects.

Effectiveness of Home-Based Telerehabilitation Interventions for Dysphagia in Patients With Head and Neck Cancer: Systematic Review.

BACKGROUND: Multimodal treatment-induced dysphagia has serious negative effects on survivors of head and neck cancer. Owing to advances in communication technologies, several studies have applied telecommunication-based interventions that incorporate swallowing exercises, education, monitoring, feedback, self-management, and communication. It is especially urgent to implement home-based remote rehabilitation in the context of the COVID-19 pandemic. However, the optimal strategy and effectiveness of remote interventions are unclear. OBJECTIVE: This systematic review aimed to examine the evidence regarding the efficacy of telerehabilitation for reducing physiological and functional impairments related to swallowing and for improving adherence and related influencing factors among head and neck cancer survivors. METHODS: The PubMed, MEDLINE, CINAHL, Embase, and Cochrane Library databases were systematically searched up to July 2023 to identify relevant articles. In total, 2 investigators independently extracted the data and assessed the methodological quality of the included studies using the quality assessment tool of the Joanna Briggs Institute. RESULTS: A total of 1465 articles were initially identified; ultimately, 13 (0.89%) were included in the systematic review. The quality assessment indicated that the included studies were of moderate to good quality. The results showed that home-based telerehabilitation improved the safety of swallowing and oral feeding, nutritional status, and swallowing-related quality of life; reduced negative emotions; improved swallowing rehabilitation adherence; was rated by participants as highly satisfactory and supportive; and was cost-effective. In addition, this review investigated factors that influenced the efficacy of telerehabilitation, which included striking a balance among swallowing training strategy, intensity, frequency, duration, and individual motor ability; treating side effects of radiotherapy; providing access to medical, motivational, and educational information; providing feedback on training; providing communication and support from speech pathologists, families, and other survivors; and addressing technical problems. CONCLUSIONS: Home-based telerehabilitation has shown great potential in reducing the safety risks of swallowing and oral feeding, improving quality of life and adherence, and meeting information needs for dysphagia among survivors of head and neck cancer. However, this review highlights limitations in the current literature, and the current research is in its infancy. In addition, owing to the diversity of patient sociodemographic, medical, physiological and functional swallowing, and behavioral factors, we recommend the development of tailored telemedicine interventions to achieve the best rehabilitation effects with the fewest and most precise interventions.

Effects of Physical Exercise Interventions for Individuals With Gynecologic Cancer: A Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Data on the efficacy of physical exercise interventions for individuals with gynecologic cancer are limited and discordant. The purpose of this review was to determine the benefits of exercise interventions in this population. LITERATURE SEARCH: The PubMed®, Web of Science, Embase® (Ovid), and Cochrane Central Register of Controlled Trials databases were searched for studies published from January 1, 2010, to November 9, 2022. DATA EVALUATION: 12 randomized controlled trials were included. A quantitative synthesis method was used to investigate the effects of exercise interventions on individuals with gynecologic cancer. SYNTHESIS: The findings indicate that physical exercise interventions may have beneficial effects on the fatigue, depression, and health-related quality of life of this patient population. However, because of the small group of studies available, the evidence must be regarded as preliminary. IMPLICATIONS FOR PRACTICE: Clinicians and oncology nurses should recommend and refer individuals with gynecologic cancer to clinic- or community-based physical exercise programs.