Study on the Association between anterior tooth Colour Preference based on the FAHP and individual factors.

BACKGROUND: The relationship between tooth colour and individual satisfaction in oral aesthetics has long been a topic of interest. In this study, we utilized the fuzzy analytic hierarchy process (FAHP) to investigate the impacts of sex and age on tooth colour preference. The findings of this study should provide a scientific basis for oral aesthetic practice. METHODS: In the current study, a random selection method was employed, and a survey was completed by 120 patients. To obtain tooth colour data, standard tooth colour charts were used. Smile photos were taken as template images using a single-lens reflex camera. The FAHP was utilized to conduct a weight analysis of tooth colour preferences among patients of different sexes and age groups. RESULTS: There were significant differences in tooth colour preference based on sex and age. Men tend to prefer the B1 colour, while women may prioritize the aesthetic effects of other colours. Additionally, as patients age, their preferences for tooth colour become more diverse. These findings offer valuable insights for oral aesthetics practitioners, enabling them to better address the aesthetic needs of patients across different sexes and ages. This knowledge can aid in the development of more personalized treatment plans that align with patients' expectations. CONCLUSION: In this study, we utilized scientific analysis methods to quantify the popularity of different tooth colours among various groups of people. By doing so, we established a scientific foundation for clinical practice. The findings of this study offer valuable insights for oral aesthetic research, enhancing our understanding of tooth colour. Additionally, these findings have practical applications in the field of oral medicine, potentially improving patients' quality of life and overall oral health.

COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection.

OBJECTIVES: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. DESIGN: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). RESULTS: 98 patients completed primary vaccination pre-pregnancy (29·6%) and antenatally (63·3%), 24·2% of whom had antenatal COVID-19, while 7·1% were unvaccinated (28·6% had antenatal COVID-19). None had severe COVID-19. Pre-pregnancy vaccination resulted in vaccination-to-infection delay of 23·3 weeks, which extended to 45·2 weeks with a booster, compared to 16·9 weeks following antenatal vaccination (p<0·001). Infections occurred at 26·2 weeks gestation in women vaccinated pre-pregnancy compared to 36·2 weeks gestation in those vaccinated during pregnancy (p<0·007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio 14·6, p=0·05) and after pre-pregnancy vaccination without a booster (hazard ratio 10·4, p=0·002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. CONCLUSION: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.

Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways.

Interactions between cells are of fundamental importance in affecting cell function. In vivo, endothelial cells and islet cells are close to each other, which makes endothelial cells essential for islet cell development and maintenance of islet cell function. We used endothelial cells to construct 3D pseudo-islets, which demonstrated better glucose regulation and greater insulin secretion compared to conventional pseudo-islets in both in vivo and in vitro trials. However, the underlying mechanism of how endothelial cells promote beta cell function localized within islets is still unknown. We performed transcriptomic sequencing, differential gene analysis, and enrichment analysis on two types of pseudo-islets to show that endothelial cells can promote the function of internal beta cells in pseudo-islets through the BTC-EGFR-JAK/STAT signaling pathway. Min6 cells secreted additional BTC after co-culture of endothelial cells with MIN6 cells outside the body. After BTC knockout in vitro, we found that beta cells functioned differently: insulin secretion levels decreased significantly, while the expression of key proteins in the EGFR-mediated JAK/STAT signaling pathway simultaneously decreased, further confirming our results. Through our experiments, we elucidate the molecular mechanisms by which endothelial cells maintain islet function in vitro, which provides a theoretical basis for the construction of pseudo-islets and islet cell transplants for the treatment of diabetes mellitus.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

Exploring and Analyzing the Systemic Delivery Barriers for Nanoparticles.

Most nanomedicines require efficient in vivo delivery to elicit diagnostic and therapeutic effects. However, en route to their intended tissues, systemically administered nanoparticles often encounter delivery barriers. To describe these barriers, we propose the term "nanoparticle blood removal pathways" (NBRP), which summarizes the interactions between nanoparticles and the body's various cell-dependent and cell-independent blood clearance mechanisms. We reviewed nanoparticle design and biological modulation strategies to mitigate nanoparticle-NBRP interactions. As these interactions affect nanoparticle delivery, we studied the preclinical literature from 2011-2021 and analyzed nanoparticle blood circulation and organ biodistribution data. Our findings revealed that nanoparticle surface chemistry affected the in vivo behavior more than other nanoparticle design parameters. Combinatory biological-PEG surface modification improved the blood area under the curve by ~418%, with a decrease in liver accumulation of up to 47%. A greater understanding of nanoparticle-NBRP interactions and associated delivery trends will provide new nanoparticle design and biological modulation strategies for safer, more effective, and more efficient nanomedicines.

Copper-Initiated Regiodivergent Chloropentafluorosulfanylation of 1,3-Enynes under Substrate Control.

A copper-catalyzed regiodivergent chloropentafluorosulfanylation strategy for 1,3-enynes using SF5Cl has been developed. The regioselectivity is dictated by the structural and substitution patterns of 1,3-enynes, enabling facile access to three classes of SF5-containing products: propargylic chlorides, 1,3-dienes, and allenes. The reaction systems involve radical species, where the transfer of a chlorine atom from SF5Cl to a carbon radical is considered the predominant pathway. Diverse types of SF5- building blocks can be synthesized through simple functional group transformations.

Evaluating drug interaction potential from cytokine release syndrome using a physiologically based pharmacokinetic model: A case study of teclistamab.

Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL-6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL-6 kinetics profiles were assessed, the mean IL-6 profile with a maximum concentration (Cmax) of IL-6 (21 pg/mL) and the IL-6 profile of the patient presenting the highest IL-6 Cmax (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC-1. For the mean IL-6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87-1.20). For the maximum IL-6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90-2.23), and minimal for caffeine and s-warfarin (mean AUC ratios 0.82-1.25). Maximum change in exposure for these substrates occurred 3-4 days after step-up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL-6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step-up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.

Comparison between computer recognition and manual measurement methods for the estimation of leaf area.

BACKGROUND AND AIMS: Leaf area (A) is a crucial indicator of the photosynthetic capacity of plants. The Montgomery equation (ME), which hypothesizes that A is proportional to the product of leaf length (L) and width (W), is a valid tool for nondestructively measuring A for many broad-leaved plants. At present, the methods used to compute L and W for ME can be broadly divided into two kinds: using computer recognition, and measuring manually. However, the potential difference in the prediction accuracy using either method has not been thoroughly examined in prior studies. METHODS: In the present study, we measured 540 Alangium chinense leaves, 489 Liquidambar formosana leaves, and 215 Liriodendron × sinoamericanum leaves, utilizing computer recognition and manual measurement methods to determine L and W. ME was used to fit the data determined by the two methods, and the goodness of fits were compared. The prediction errors of A were analyzed by examining the correlations with two leaf symmetry indices (areal ratio of the left side to the right side, and standardized index for bilateral asymmetry), as well as the leaf shape complexity index (the leaf dissection index). KEY RESULTS: The results indicate that there is a neglectable difference in the estimation of A between both methods. This further validates that ME is an effective method for estimating A in broad-leaved tree species, including those with lobes. Additionally, leaf shape complexity significantly influenced the estimation of A. CONCLUSIONS: These results show that the use of computer recognition and manual measurement in the field are both effective and feasible, although the influence of leaf shape complexity should be considered when applying ME to estimate A in the future.

Direct shear behaviors of excavated clay reinforced with geocomposite drainage layer encapsulated in thin sand layers.

The objective of this study is to assess the effectiveness of a novel structure comprising a geocomposite drainage layer and a thin sand layer (GDL + sand) in mitigating the rapid dumping of excavated clay and its associated issues, such as landslides. Two sets of direct shear tests were conducted to investigate the influence of sand layer thickness and compaction degree on the interface shear behavior of the GDL + sand structure. As the sand layer thickness increased, both the interface shear strength and friction angle gradually increased, first more sharply and then at a slower rate toward stability, while the interface cohesion decreased gradually. The optimal sand layer thickness for achieving the most effective reinforcement in stabilizing the clay was identified as 10 mm. A higher sand layer compaction degree was found to result in increased interface shear strength, interface friction angle, and interface cohesion. Building on these findings, the reinforcing efficiency of the GDL + sand structure was investigated through mechanism analysis in comparison to that of a geogrid + sand structure and GDL structure as per the interface friction coefficient. The ranking of interface friction coefficients among the three structures emerged as: geogrid + sand > GDL + sand > GDL. These results suggests that the GDL + sand structure exhibits superior reinforcement efficiency compared to the GDL structure and offers better drainage efficiency than the geogrid + sand structure.

Specific human CYP enzymes-dependent mutagenicity of tris(2-butoxyethyl) phosphate (an organophosphorus flame retardant) in human and hamster cell lines.

Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4.

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury.

BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.

Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis.

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague-Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Pan-viral Antibody Repertoire of Aqueous Humor in Cytomegalovirus Uveitis.

PURPOSE: The identification of infectious etiologies is important in the management of uveitis. Ocular fluid testing is required but multiplex testing faces challenges due to limited volume sampled. The determination of antibody repertoire of aqueous humor (AH) is not possible with conventional assays. We hence investigated the use of a highly multiplexable serological assay VirScan, a Phage ImmunoPrecipitation Sequencing (PhIP-Seq) library derived from the sequences of over 200 viruses, to determine the antibody composition of AH in uveitis patients. DESIGN: Prospective case control study METHODS: We analyzed the paired AH and plasma samples of 11 immunocompetent patients with active PCR-positive CMV anterior uveitis, and the AH of 34 control cataract surgery patients with no known uveitis in an institutional practice. The samples were tested using VirScan PhIP-Seq and the entire pan-viral antibody repertoire was determined using peptide tile ranking by normalized counts to identify significant antibodies enrichment against all viruses with human tropism. RESULTS: Significant enrichment of antibodies to Herpesviridae, Picornavirdae and Paramyxoviridae were detectable in 20 microliters of AH samples from CMV uveitis patients and controls. CMV uveitis patients had relative enrichment of anti-CMV antibodies in AH compared to their plasma. Epitope-level mapping identified significant enrichment of antibodies against CMV tegument protein pp150 (p=1.5e-06) and envelope glycoprotein B (p=0.0045) in the AH compared to controls. CONCLUSIONS: Our proof-of-concept study not only shed light on the antibody repertoire of AH but expands the utility of PhIP-Seq to future studies to detect antibodies in AH in the study of inflammatory eye diseases.

Predictive value of miR-7110-5p and miR-223-3p as biomarkers for sepsis secondary to pneumonia.

BACKGROUND: Investigating the secondary sepsis of pneumonia is of great significance for rapid diagnosis and early treatment of sepsis. OBJECTIVE: This study aimed to investigate the predictive value of micro ribonucleic acids (miRNA) 7110-5p and miR-223-3p in sepsis secondary to pneumonia. A miRNA microarray was used to analyze the differences in miRNA expression between patients with pneumonia and those with sepsis secondary to pneumonia. METHODS: The study included a total of 50 patients with pneumonia and 42 patients with sepsis secondary to pneumonia. Quantitative polymerase chain reaction analysis was conducted to measure the circulating miRNA expression levels in patients and assess their correlations with clinical characteristics and prognosis. In this study, nine miRNAs - hsa-miR-4689-5p, hsa-miR-4621-5p, hsa-miR-6740-5p, hsa-miR-7110-5p, hsa-miR-765, hsa-miR-940, hsa-miR-213-5p, hsa-miR-223-3p, and hsa-miR-122 - met the screening criteria of having a fold change ⩾ 2 or < 0.5; p< 0.01 indicated significant differences in the results. RESULTS: The expression levels of miR-7110-5p and miR-223-3p differed between the two patient groups, being up-regulated in the plasma of patients with sepsis secondary to pneumonia. miR-7110-5p and miR-223-3p showed higher expression levels in both patients with pneumonia and sepsis compared to healthy controls. Moreover, the receiver operating characteristic curve revealed that the areas under the curve for predicting pneumonia using miR-7110-5p were 0.781 while those for predicting sepsis secondary to pneumonia were 0.862. For miR-223-3p, the corresponding values for predicting pneumonia and sepsis secondary to pneumonia were 0.879 and 0.924, respectively. However, there were no significant differences in the levels of miR-7110-5p and miR-223-3p between the plasma of survived and deceased patients with sepsis. CONCLUSIONS: MiR-7110-5p and miR-223-3p have the potential to serve as biological indicators for predicting sepsis secondary to pneumonia.

Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice.

Adaptation to hypoxia is a major challenge for the survival of Mycobacterium tuberculosis (Mtb) in vivo. Interferon (IFN)-γ-producing CD8+ T cells contribute to control of Mtb infection, in part by promoting antimicrobial activities of macrophages. Whether Mtb counters these responses, particularly during hypoxic conditions, remains unknown. Using metabolomic, proteomic and genetic approaches, here we show that Mtb induced Rv0884c (SerC), an Mtb phosphoserine aminotransferase, to produce D-serine. This activity increased Mtb pathogenesis in mice but did not directly affect intramacrophage Mtb survival. Instead, D-serine inhibited IFN-γ production by CD8+ T cells, which indirectly reduced the ability of macrophages to restrict Mtb upon co-culture. Mechanistically, D-serine interacted with WDR24 and inhibited mTORC1 activation in CD8+ T cells. This decreased T-bet expression and reduced IFN-γ production by CD8+ T cells. Our findings suggest an Mtb evasion mechanism where pathogen metabolic adaptation to hypoxia leads to amino acid-dependent suppression of adaptive anti-TB immunity.

Recombinant Beauveria bassiana expressing Bacillus thuringiensis toxin Cyt1Aa: a promising approach for enhancing Aedes mosquito control.

The entomopathogenic fungus Beauveria bassiana provides an eco-friendly substitute to chemical insecticides for mosquito control. Nevertheless, its widespread application has been hindered by its comparatively slow efficacy in eliminating mosquitoes. To augment the potency of B. bassiana against Aedes mosquitoes, a novel recombinant strain, Bb-Cyt1Aa, was developed by incorporating the Bacillus thuringiensis toxin gene Cyt1Aa into B. bassiana. The virulence of Bb-Cyt1Aa was evaluated against Aedes aegypti and Aedes albopictus using insect bioassays. Compared to the wild-type (WT) strain, the median lethal time (LT50) for A. aegypti larvae infected with Bb-Cyt1Aa decreased by 33.3% at a concentration of 1 × 108 conidia/mL and by 22.2% at 1 × 107 conidia/mL. The LT50 for A. aegypti adults infected with Bb-Cyt1Aa through conidia ingestion was reduced by 37.5% at 1 × 108 conidia/mL and by 33.3% at 1 × 107 conidia/mL. Likewise, the LT50 for A. aegypti adults infected with Bb-Cyt1Aa through cuticle contact decreased by 33.3% and 30.8% at the same concentrations, respectively. Furthermore, the Bb-Cyt1Aa strain also demonstrated increased toxicity against both larval and adult A. albopictus, when compared to the WT strain. In conclusion, our study demonstrated that the expression of B. thuringiensis toxin Cyt1Aa in B. bassiana enhanced its virulence against Aedes mosquitoes. This suggests that B. bassiana expressing Cyt1Aa has potential value for use in mosquito control. IMPORTANCE: Beauveria bassiana is a naturally occurring fungus that can be utilized as a bioinsecticide against mosquitoes. Cyt1Aa is a delta-endotoxin protein produced by Bacillus thuringiensis that exhibits specific and potent insecticidal activity against mosquitoes. In our study, the expression of this toxin Cyt1Aa in B. bassiana enhances the virulence of B. bassiana against Aedes aegypti and Aedes albopictus, thereby increasing their effectiveness in killing mosquitoes. This novel strain can be used alongside chemical insecticides to reduce dependence on harmful chemicals, thereby minimizing negative impacts on the environment and human health. Additionally, the potential resistance of B. bassiana against mosquitoes in the future could be overcome by acquiring novel combinations of exogenous toxin genes. The presence of B. bassiana that expresses Cyt1Aa is of significant importance in mosquito control as it enhances genetic diversity, creates novel virulent strains, and contributes to the development of safer and more sustainable methods of mosquito control.

Indian Ocean temperature anomalies predict long-term global dengue trends.

Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.

Panax notoginseng Saponins Activate Nuclear Factor Erythroid 2-Related Factor 2 to Inhibit Ferroptosis and Attenuate Inflammatory Injury in Cerebral Ischemia-Reperfusion.

Panax notoginseng saponins (PNS), the primary medicinal ingredient of Panax notoginseng, mitigates cerebral ischemia-reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. In this study, we aimed to investigate the effects of PNS on ferroptosis and inflammation in CIRI. We induced ferroptosis in SH-SY5Y cells via erastin stimulation and oxygen glucose deprivation/re-oxygenation (OGD/R) in vitro. Furthermore, we determined the effect of PNS treatment in a rat model of middle cerebral artery occlusion/reperfusion and assessed the underlying mechanism. We also analyzed the changes in the expression of ferroptosis-related proteins and inflammatory factors in the established rat model. OGD/R led to an increase in the levels of ferroptosis markers in SH-SY5Y cells, which were reduced by PNS treatment. In the rat model, combined treatment with an Nrf2 agonist, Nrf2 inhibitor, and PNS-Nrf2 inhibitor confirmed that PNS promotes Nrf2 nuclear localization and reduces ferroptosis and inflammatory responses, thereby mitigating brain injury. Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI.

Overexpression of an Integument Esterase Gene LbEST-inte4 Infers the Malathion Detoxification in Liposcelis bostrychophila (Psocoptera: Liposcelididae).

Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.