Study on Thermophysical Properties and Phase Change Regulation Mechanism of Optically-Controlled Phase Change Materials: Synthesis, Crystal Structure and Molecular Dynamics.

Optically-controlled phase change materials, which are prepared by introducing molecular photoswitches into traditional phase change materials (PCMs), can convert and store solar energy into photochemical enthalpy and phase change enthalpy. However, the thermophysical properties of optically controlled PCMs, which are crucial in the practical, are rarely paid attention to. 4-(phenyldiazenyl)phenyl decanoate (Azo-A-10) is experimentally prepared as an optically-controlled PCMs, whose energy storage density is 210.0 kJ·kg-1, and the trans single crystal structure is obtained. The density, phase transition temperature, thermal conductivity, and other parameters in trans state are measured experimentally. Furthermore, a microscopic model of Azo-A-10 is established, and the thermophysical properties are analyzed based on molecular dynamics. The results show that the microstructure parameter (order parameters) and thermophysical properties (density, radial distribution function, self-diffusion coefficient, phase change temperature, and thermal conductivity) of partially or completely isomerized Azo-A-10, which are challenging to observe in experiments, can be predicted by molecular dynamics simulation. The optically-controlled phase change mechanism can be clarified according to the differences in microstructure. The optically-controlled switchability of thermophysical properties of an optically-controlled PCM is analyzed. This study provides ideas for the improvement, development, and application of optically-controlled PCMs in the future.

The role of the Notch signaling pathway in bacterial infectious diseases.

The Notch signaling pathway is the most crucial link in the normal operation and maintenance of physiological functions of mammalian life processes. Notch receptors interact with ligands and this leads to three cleavages and goes on to enter the nucleus to initiate the transcription of target genes. The Notch signaling pathway deeply participates in the differentiation and function of various cells, including immune cells. Recent studies indicate that the outcomes of Notch signaling are changeable and highly dependent on different bacterial infection. The Notch signaling pathway plays a different role in promoting and inhibiting bacterial infection. In this review, we focus on the latest research findings of the Notch signaling pathway in bacterial infectious diseases. The Notch signaling pathway is critically involved in a variety of development processes of immunosuppression of different APCs. The Notch signaling pathway leads to functional changes in epithelial cells to aggravate tissue damage. Specifically, we illustrate the regulatory mechanism of the Notch signaling pathway in various bacterial infections, such as Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, Mycobacterium leprae, Helicobacter pylori, Klebsiella pneumoniae, Bacillus subtilis, Staphylococcus aureus, Ehrlichia chaffeensis and sepsis. Collectively, this review will not only help beginners intuitively and systematically understand the Notch signaling pathway in bacterial infectious diseases but also help experts to generate fresh insight in this field.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Impact of baseline and trajectory of the atherogenic index of plasma on incident diabetic kidney disease and retinopathy in participants with type 2 diabetes: a longitudinal cohort study.

BACKGROUND: Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. METHODS: The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. RESULTS: During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36-2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62-2.91) and 84% (95% CI 1.46-2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. CONCLUSIONS: Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.

Association between subchorionic hematoma in the first trimester and outcomes of singleton pregnancies achieved through assisted reproductive technology: a systematic review and meta-analysis.

PURPOSE: To evaluate the association between first trimester (≤ 12 weeks gestation) subchorionic hemorrhage (SCH), and maternal and neonatal outcomes in women who conceived with the help of assisted reproductive technique (ART). METHODS: PubMed, Embase, Web of Science, and Scopus databases were searched for observational studies that specifically focused on women who achieved pregnancy via ART and investigated the relationship between early pregnancy (within 12 weeks of gestation) SCH and maternal and neonatal outcomes. Only studies with singleton pregnancies and reporting data on the comparator group (women without SCH) were included. Primary outcomes of interest included incidences of early (within 20 weeks of gestation) pregnancy loss, preterm delivery, caesarean section, and live birth rates. Pooled effect sizes were reported as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Nine studies were included. All studies had a cohort design. In all studies, the primary assisted reproduction technique used was in-vitro fertilization (IVF). Compared to pregnancies without SCH, women with diagnosed early pregnancy SCH have a similar risk of preterm birth (< 37 weeks) (OR 1.01, 95% CI 0.83, 1.22), low birth weight (< 2500 g) (OR 1.01, 95% CI 0.59, 1.73) and fetal growth restriction (OR 1.57, 95% CI 0.62, 4.02). The gestational age (in weeks) (weighted mean difference (WMD) - 0.06, 95% CI - 0.18, 0.06) and the birth weight (in grams) (WMD - 16.5, 95% CI - 62.9, 29.8) were also similar in the two groups. The odds of early pregnancy loss (OR 1.39, 95% CI 0.97, 2.01), live birth (OR 0.77, 95% CI 0.55, 1.08) and caesarean delivery (OR 0.97, 95% CI 0.81, 1.16) were statistically similar in both groups. The risk of maternal adverse outcomes such as gestational diabetes (OR 0.98, 95% CI 0.74, 1.29), hypertensive disorder (OR 0.95, 95% CI 0.63, 1.43), premature rupture of membranes (PROM) (OR 1.36, 95% CI 0.90, 2.05) and placental abruption (OR 2.44, 95% CI 0.57, 10.5) was also similar in both the groups. There was no evidence of publication bias. CONCLUSION: The findings suggest that SCH may not significantly increase the risk of adverse maternal and perinatal outcomes in pregnancies conceived through ART, particularly IVF. TRIAL REGISTRATION: PROSPERO registration number CRD42024533996.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

Sedentary behaviour among elderly patients after total knee arthroplasty and its influencing factors.

To understand the status of sedentary behaviour in elderly patients after total knee arthroplasty and analyse its influencing factors so as to provide a reference for developing targeted interventions. Conveniently selected elderly patients undergoing total knee arthroplasty (> 6 months) in a tertiary hospital in Jiangsu Province were investigated using a general information questionnaire, the Charlson Comorbidity Index, patients' self-reported sedentary behaviour information, the WOMAC Score, The Groningen Orthopaedic Social Support Scale, and Lee's Fatigue. The median daily sedentary time was 5.5 h (4.5 h, 6.625 h) in 166 elderly patients after total knee arthroplasty, of whom 82 (49.40%) showed sedentary behaviour (≥ 6 h per day). Logistic regression analysis showed that being retired/unemployed (OR = 8.550, 95% CI 1.732-42.207, P = 0.0084), having a CCI score ≥ 3 (OR = 9.018, 95% CI 1.288-63.119, P < 0.0001), having high WOMAC scores (OR = 1.783, 95% CI 1.419-2.238, P < 0.0001), having a high social support score (OR = 1.155, 95% CI 1.031-1.294, P = 0.0130), and having a fatigue score ≥ 5 (OR = 4.848, 95% CI 1.084-21.682, P = 0.0389) made patients more likely to be sedentary. The sedentary time of elderly patients after total knee arthroplasty is long, and sedentary behaviour is common among them. Healthcare professionals should develop targeted sedentary behaviour interventions based on the influencing factors of sedentary behaviour in order to reduce the occurrence of sedentary behaviour in elderly patients after total knee arthroplasty.

Which SDM Model, CLIMEX vs. MaxEnt, Best Forecasts Aeolesthes sarta Distribution at a Global Scale under Climate Change Scenarios?

A precise evaluation of the risk of establishing insect pests is essential for national plant protection organizations. This accuracy is crucial in negotiating international trade agreements for forestry-related commodities, which have the potential to carry pests and lead to unintended introductions in the importing countries. In our study, we employed both mechanistic and correlative niche models to assess and map the global patterns of potential establishment for Aeolesthes sarta under current and future climates. This insect is a significant pest affecting tree species of the genus Populus, Salix, Acer, Malus, Juglans, and other hardwood trees. Notably, it is also categorized as a quarantine pest in countries where it is not currently present. The mechanistic model, CLIMEX, was calibrated using species-specific physiological tolerance thresholds, providing a detailed understanding of the environmental factors influencing the species. In contrast, the correlative model, maximum entropy (MaxEnt), utilized species occurrences and spatial climatic data, offering insights into the species' distribution based on observed data and environmental conditions. The projected potential distribution from CLIMEX and MaxEnt models aligns well with the currently known distribution of A. sarta. CLIMEX predicts a broader global distribution than MaxEnt, indicating that most central and southern hemispheres are suitable for its distribution, excluding the extreme northern hemisphere, central African countries, and the northern part of Australia. Both models accurately predict the known distribution of A. sarta in the Asian continent, and their projections suggest a slight overall increase in the global distribution range of A. sarta with future changes in climate temperature, majorly concentrating in the central and northern hemispheres. Furthermore, the models anticipate suitable conditions in Europe and North America, where A. sarta currently does not occur but where its preferred host species, Populus alba, is present. The main environmental variables associated with the distribution of A. sarta at a global level were the average annual temperature and precipitation rate. The predictive models developed in this study offer insights into the global risk of A. sarta establishment and can be valuable for monitoring potential pest introductions in different countries. Additionally, policymakers and trade negotiators can utilize these models to make science-based decisions regarding pest management and international trade agreements.

Building a reference indicator model using co-kriging interpolation to determine the geographical origin of the flighted spongy moth complex in China.

Using stable isotopes to detect and analyze the geographical origin of insects represents an important traceability technology, which requires a rich isotope database. In this study, we representatively sampled the Chinese provinces where flighted spongy moth complex (FSMC) has been reported and, for the first time, used co-kriging interpolation to predict the distribution patterns of FSMC δ13 C values in the main distribution areas. From 2020 to 2022, we set up 60 traps in 12 provinces and cities in China and collected 795 FSMCs. Then, 6 main climatic factors were obtained by multi-collinearity screening from 21 types of meteorological data collected at the sample plots, and a correlation analysis was carried out by combining longitude, latitude, and altitude data with the δ13 C values of FSMC. Next, we performed a co-kriging interpolation using the 2 climatic factors with the highest correlation (isothermality and altitude) and the δ13 C values of FSMC. A cross-validation was performed to systematically test 11 candidate models and select the best semi-variogram model ("Exponential"), which was then used to build a co-kriging interpolation model. The geographical distribution patterns of the FSMC δ13 C values obtained from the 2 interpolation models (i.e., interpolated with isothermality and altitude, respectively) were almost the same. Moreover, the δ13 C values varied significantly at the regional scale, showing regular changes in spatial distribution. Overall, the reference indicator map of the δ13 C values generated from stable isotopes can be used to greatly improve the efficiency of discrimination analyses on the geographical origin of FSMC.

Effectiveness and safety of tripterygium wilfordii poly-glycosides on glomerulonephritis: a systematic review and meta-analysis.

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

Identification of novel dual-target 4-hydroxyphenylpyruvate dioxygenase & phytoene dehydrogenase inhibitors via multiple virtual screening.

Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.

In silico designed novel multi-epitope mRNA vaccines against Brucella by targeting extracellular protein BtuB and LptD.

Brucella, a gram-negative intracellular bacterium, causing Brucellosis, a zoonotic disease with a range of clinical manifestations, from asymptomatic to fever, fatigue, loss of appetite, joint and muscle pain, and back pain, severe patients have developed serious diseases affecting various organs. The mRNA vaccine is an innovative type of vaccine that is anticipated to supplant traditional vaccines. It is widely utilized for preventing viral infections and for tumor immunotherapy. However, research regarding its effectiveness in preventing bacterial infections is limited. In this study, we analyzed the epitopes of two proteins of brucella, the TonB-dependent outer membrane receptor BtuB and the LPS assembly protein LptD, which is involved in nutrient transport and LPS synthesis in Brucella. In order to effectively stimulate cellular and humoral immunity, we utilize a range of immunoinformatics tools such as VaxiJen, AllergenFPv.1.0 and SignalP 5.0 to design proteins. Finally, five cytotoxic T lymphocyte (CTL) cell epitopes, ten helper T lymphocyte (HTL) cell epitopes, and eight B cell epitopes were selected to construct the vaccine. Computer simulations are also used to verify the immune response of the vaccine. The codon optimization, in silico cloning showed that the vaccine can efficiently transcript and translate in E. coli. The secondary structure of mRNA vaccines and the secondary and tertiary structures of vaccine peptides were predicted and then docked with TLR-4. Finally, the stability of the developed vaccine was confirmed through molecular dynamics simulation. These analyses showed that the design the multi-epitope mRNA vaccine could potentially target extracellular protein of prevalent Brucella, which provided novel strategies for developing the vaccine.

Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

The development of a human Brucella mucosal vaccine: What should be considered?

Brucellosis is a chronic infectious disease that is zoonotic in nature. Brucella can infect humans through interactions with livestock, primarily via the digestive tract, respiratory tract, and oral cavity. This bacterium has the potential to be utilized as a biological weapon and is classified as a Category B pathogen by the Centers for Disease Control and Prevention. Currently, there is no approved vaccine for humans against Brucella, highlighting an urgent need for the development of a vaccine to mitigate the risks posed by this pathogen. Brucella primarily infects its host by adhering to and penetrating mucosal surfaces. Mucosal immunity plays a vital role in preventing local infections, clearing microorganisms from mucosal surfaces, and inhibiting the spread of pathogens. As mucosal vaccine strategies continue to evolve, the development of a safe and effective mucosal vaccine against Brucella appears promising.This paper reviews the immune mechanism of mucosal vaccines, the infection mechanism of Brucella, successful Brucella mucosal vaccines in animals, and mucosal adjuvants. Additionally, it elucidates targeting and optimization strategies for mucosal vaccines to facilitate the development of human vaccines against Brucella.

Development of a novel multi-epitope vaccine for brucellosis prevention.

Brucellosis, a zoonotic disease caused by Brucella, presents a significant threat to both animal and human health. In animals, the disease can lead to infertility, miscarriage, and high fever, while in humans, symptoms may include recurrent fever, fatigue, sweating, hepatosplenomegaly, and joint and muscle pain following infection. Treatment often involves long-term antibiotic therapy, placing a substantial psychological and financial burden on patients. While vaccination is crucial for prevention, current animal vaccines have drawbacks such as residual virulence, and a safe and effective human vaccine is lacking. Hence, the development of a vaccine for brucellosis is imperative. In this study, we utilized bioinformatics methods to design a multi-epitope vaccine targeting Brucella. Targeting Heme transporter BhuA and polysaccharide export protein, we identified antigenic epitopes, including six cytotoxic T lymphocyte (CTL) dominant epitopes, six helper T lymphocyte (HTL) dominant epitopes, one conformation B cell dominant epitope, and three linear B cell dominant epitopes. By linking these epitopes with appropriate linkers and incorporating a Toll-like receptor (TLR) agonist (human beta-defensin-2) and an auxiliary peptide (Pan HLA-DR epitopes), we constructed the multi-epitope vaccine (MEV). The MEV demonstrated high antigenicity, non-toxicity, non-allergenicity, non-human homology, stability, and solubility. Molecular docking analysis and molecular dynamics simulations confirmed the interaction and stability of the MEV with receptors (MHCI, MHCII, TLR4). Codon optimization and in silico cloning validated the translation efficiency and successful expression of MEV in Escherichia coli. Immunological simulations further demonstrated the efficacy of MEV in inducing robust immune responses. In conclusion, our findings suggest that the engineered MEVs have the potential to stimulate both humoral and cellular immune responses, offering valuable insights for the future development of safe and efficient Brucella vaccines.

Universal subunit vaccine protects against multiple SARS-CoV-2 variants and SARS-CoV.

Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.

Occurrence and potential diffusion of pine wilt disease mediated by insect vectors in China under climate change.

BACKGROUND: Pine wilt disease (PWD), a major international quarantined forest pest, causes serious ecological and economic damage to Pinus species in Asia and Europe. In China, PWD has spread northeasterly and northwesterly beyond its original northern limits. Consequently, an evaluation of the insect vector-mediated occurrence and potential diffusion of PWD is needed to identify important transmission routes and control the spread of disease. RESULTS: An optimized MaxEnt model was used to assess the current and future geographical distribution of Bursaphelenchus xylophilus and its insect vectors in China. The predicted suitable area for B. xylophilus colonization is currently 212.32 × 104 km2 and mainly concentrated in Central, East, Southwest and South China, although is anticipated to include the northwestern regions of China in the future. As for the insect vectors, Monochamus alternatus and M. saltuarius are expected to spread toward the northwest and southwest, respectively. The maximum predicted dispersion area of PWD mediated by M. alternatus, M. saltuarius and both species was 91.85 × 104, 218.76 × 104 and 29.99 × 104 km2, respectively, with potential diffusion areas being anticipated to increase in the future. Both the suitable probabilities and areas of B. xylophilus and its insect vectors were found to vary substantially along the latitudinal gradient, with the latitudinal range of these species being predicted to expand in the future. CONCLUSION: This is the first study to investigate the potential diffusion areas of PWD mediated by insect vectors in China, and our finding will provide a vital theoretical reference and empirical basis for developing more effective management strategies for the control of PWD in China. © 2024 Society of Chemical Industry.

A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies.

SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.