Outcomes of Ticagrelor Versus High-dose Clopidogrel in CYP2C19 Intermediate Metabolizer Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes.

ABSTRACT: Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.

An intranasally administered adenovirus-vectored SARS-CoV-2 vaccine induces robust mucosal secretory IgA.

BACKGROUNDThe level of nasal spike-specific secretory IgA (sIgA) is inversely correlated with the risk of SARS-CoV-2 Omicron infection. This study aimed to evaluate the safety and immunogenicity of intranasal vaccination using Ad5-S-Omicron (NB2155), a replication-incompetent human type 5 adenovirus carrying Omicron BA.1 spike.METHODSAn open-label, single-center, investigator-initiated trial was carried out on 128 health care workers who had never been infected with SARS-CoV-2 and had previously received 2 or 3 injections of inactivated whole-virus vaccines, with the last dose given 3-19 months previously (median 387 days, IQR 333-404 days). Participants received 2 intranasal sprays of NB2155 at 28-day intervals between November 30 and December 30, 2022. Safety was evaluated by solicited adverse events and laboratory tests. The elevation of nasal mucosal spike-specific sIgA and serum neutralizing activities were assessed. All participants were monitored for infection by antigen tests, disease symptoms, and the elevation of nucleocapsid-specific sIgA in the nasal passage.RESULTSThe vaccine-related solicited adverse events were mild. Nasal spike-specific sIgA against 10 strains had a mean geometric mean fold increase of 4.5 after the first dose, but it increased much higher to 51.5 after the second dose. Serum neutralizing titers also increased modestly to 128.1 (95% CI 74.4-220.4) against authentic BA.1 and 76.9 (95% CI 45.4-130.2) against BA.5 at 14 days after the second dose. Due to the lifting of the zero-COVID policy in China on December 7, 2022, 57.3% of participants were infected with BA.5 between days 15 and 28 after the first dose, whereas no participants reported having any symptomatic infections between day 3 and day 90 after the second dose. The elevation of nasal nucleocapsid-specific sIgA on days 0, 14, 42, and 118 after the first dose was assessed to verify that these 2-dose participants had no asymptomatic infections.CONCLUSIONA 2-dose intranasal vaccination regimen using NB2155 was safe, was well tolerated, and could dramatically induce broad-spectrum spike-specific sIgA in the nasal passage. Preliminary data suggested that the intranasal vaccination may establish an effective mucosal immune barrier against infection and warranted further clinical studies.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR2300070346).FUNDINGNatural Science Foundation of China, Guangzhou Laboratory, The First Affiliated Hospital of Guangzhou Medical University.

Highly enhanced chiroptical effect from self-inclusion helical nanocrystals of tetraphenylethylene bimacrocycles.

The helical structure is often the key factor for forming and enhancing chiroptical properties, such as circular dichroism (CD) and circular polarized luminescence (CPL) effects. However, no matter whether helical molecules or helical aggregates, they usually display modest chiroptical signals, which limits their practical applications. Herein, chiral tetraphenylethylene (TPE) bimacrocycles prepared in almost quantitative yield show strong and repeatable CD signals up to more than 7000 mdeg, which is very rare for general organic compounds, besides emitting very strong CPL light with an absolute g lum value up to 6.2 × 10-2. It is found that the superhelices formed by self-inclusion between the cavity and outward cyclohexyl ring of TPE bimacrocycles in crystal state are the key factor for highly enhanced chiroptical effect, and the self-inclusion superhelices in assemblies are confirmed by High Resolution Transmission Electron Microscopy (HR-TEM), Powder X-ray Diffraction (XRD) and Fourier Transform Infrared Spectrometry (FT-IR) data. Furthermore, the chiral TPE bimacrocycle shows great potential in chiral recognition and chiral analysis not only for chiral acids but also for chiral amines, chiral amino acids, and neutral chiral alcohol. Using self-inclusion helical nanocrystals of chiral macrocycles, this work provides a new strategy for chiroptical materials with excellent chiroptical properties.

Progress on deep learning in genomics.

With the rapid growth of data driven by high-throughput sequencing technologies, genomics has entered an era characterized by big data, which presents significant challenges for traditional bioinformatics methods in handling complex data patterns. At this critical juncture of technological progress, deep learning-an advanced artificial intelligence technology-offers powerful capabilities for data analysis and pattern recognition, revitalizing genomic research. In this review, we focus on four major deep learning models: Convolutional Neural Network(CNN), Recurrent Neural Network(RNN), Long Short-Term Memory(LSTM), and Generative Adversarial Network(GAN). We outline their core principles and provide a comprehensive review of their applications in DNA, RNA, and protein research over the past five years. Additionally, we also explore the use of deep learning in livestock genomics, highlighting its potential benefits and challenges in genetic trait analysis, disease prevention, and genetic enhancement. By delivering a thorough analysis, we aim to enhance precision and efficiency in genomic research through deep learning and offer a framework for developing and applying livestock genomic strategies, thereby advancing precision livestock farming and genetic breeding technologies.

Droplet-based single-cell sequencing: Strategies and applications.

Notable advancements in single-cell omics technologies have not only addressed longstanding challenges but also enabled unprecedented studies of cellular heterogeneity with unprecedented resolution and scale. These strides have led to groundbreaking insights into complex biological systems, paving the way for a more profound comprehension of human biology and diseases. The droplet microfluidic technology has become a crucial component in many single-cell sequencing workflows in terms of throughput, cost-effectiveness, and automation. Utilizing a microfluidic chip to encapsulate and profile individual cells within droplets has significantly improved single-cell research. Therefore, this review aims to comprehensively elaborate the droplet microfluidics-assisted omics methods from a single-cell perspective. The strategies for using droplet microfluidics in the realms of genomics, epigenomics, transcriptomics, and proteomics analyses are first introduced. On this basis, the focus then turns to the latest applications of this technology in different sequencing patterns, including mono- and multi-omics. Finally, the challenges and further perspectives of droplet-based single-cell sequencing in both foundational research and commercial applications are discussed.

Photothermal Catalytic Removal of 1,2-DCE with High HCl Selectivity over the Brønsted Acid-Enriched Sulfur-Doped MOFs.

Chlorinated volatile organic compounds come from a wide range of sources and are highly toxic, posing a serious threat to biological health and the environment. Herein, a high-efficiency and energy-saving photothermal synergistic catalytic oxidation method was developed for the removal of 1,2-dichloroethane (1,2-DCE). Compared to traditional thermocatalysis, the 1,2-DCE conversion over Ru-U6S in photothermal synergistic catalysis at 340 °C increased by approximately 44% not only reducing energy consumption but also avoiding the instability of MOF structure caused by high reaction temperature. The excellent photothermal catalytic oxidation activity was derived from the synergistic effect of photo- and thermocatalysis. Ru-U6S demonstrated excellent 1,2-DCE adsorption capacity and stronger light utilization and could produce more reactive oxygen species (•OH and •O2-) after light illumination, which participated in the oxidation reaction, promoting the release of the active site of the catalyst. The results of H2O-TPD and NH3-DRIFTS exhibited that the use of S-containing ligands in the synthesis process increased the hydroxyl groups and Brønsted acid sites, significantly improved the selectivity of CO2 and HCl in the oxidation process, and reduced the release of chlorine-containing byproducts. This work provides a high-efficiency and energy-saving strategy for removing chlorinated volatile organic compounds and increasing the selectivity of ideal products directly with MOFs directly.

SRSF2 is essential for maintaining pancreatic beta-cell identity and regulating glucose homeostasis in mice.

Diabetes is characterized by decreased beta-cell mass and islet dysfunction. The splicing factor SRSF2 plays a crucial role in cell survival, yet its impact on pancreatic beta cell survival and glucose homeostasis remains unclear. We observed that the deletion of Srsf2 specifically in beta cells led to time-dependent deterioration in glucose tolerance, impaired insulin secretion, decreased islet mass, an increased number of alpha cells, and the onset of diabetes by the age of 10 months in mice. Single-cell RNA sequencing (scRNA-seq) analyses revealed that, despite an increase in populations of unfolded protein response (UPR)-activated and undifferentiated beta cells within the SRSF2_KO group, there was a notable decrease in the expression of UPR-related and endoplasmic reticulum (ER)-related genes, accompanied by a loss of beta-cell identity. This suggests that beta cells have transitioned from an adaptive phase to a maladaptive phase in islets of 10-month-old SRSF2_KO mice. Further results demonstrated that deletion of SRSF2 caused decreased proliferation in beta cells within 3-month-old islets and Min6 cells. These findings underscore the essential role of SRSF2 in controlling beta-cell proliferation and preserving beta-cell function in mice.

Reduction in the risk of contrast-induced nephropathy using enhanced external counter-pulsation in patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy of EECP in the prevention of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD). METHODS: A prospective trial was undertaken in the participants. A total of 280 patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 who underwent percutaneous coronary artery procedures were enrolled and divided into two groups: the control group (n = 100) and the EECP group (n = 180). All patients received extracellular fluid volume expansion therapy with 0.9% normal saline, and patients in the EECP groups were also treated with EECP. The renal function indexes of the two groups were determined 48-72 h after coronary artery procedures. RESULTS: In the EECP group, the BUN and serum creatinine (Scr) after coronary artery procedures were significantly lower than those before coronary artery procedures (BUN: 8.4 ± 3.5 vs. 6.6 ± 2.7 mmol/L, p < 0.001; Scr: 151.9 ± 44.7 vs. 144.5 ± 48.3 µmol/L, p < 0.001), while the eGFR was significantly increased (43.6 ± 11.4 vs. 47.1 ± 13.9 ml/min/1.73 m2, p < 0.001). The degree of Scr elevation was lower in the EECP group than in the control group (12.4 ± 15.0 vs. 20.9 ± 24.8 µmol/L, p = 0.026). Additionally, the EECP group had a lower incidence of post-procedures Scr elevation than the control group (36.5 vs. 48.0%, p = 0.042), a higher incidence of post-procedures eGFR elevation (62.2 vs. 48.0%, p = 0.021), and a lower risk of CIN (1.1 vs. 6.0%, p = 0.019). CONCLUSION: EECP therapy has a protective effect on renal function and can reduce the risk of CIN in patients with CKD.

Inkjet-printed flexible V2CTx film electrodes with excellent photoelectric properties and high capacities for energy storage device.

Energy storage devices are progressively advancing in the light-weight, flexible, and wearable direction. Ti3C2Tx flexible film electrodes fabricated via a non-contact, cost-effective, high-efficiency, and large-scale inkjet printing technology were capable of satisfying these demands in our previous report. However, other MXenes that can be employed in flexible energy storage devices remain undiscovered. Herein, flexible V2CTx film electrodes (with the low formula weight vs Ti3C2Tx film electrodes) with both high capacities and excellent photoelectric properties were first fabricated. The area capacitances of V2CTx film electrodes reached 531.3-5787.0 µF⋅cm-2 at 5 mV⋅s-1, corresponding to the figure of merits (FoMs) of 0.07-0.15. Noteworthy, V2CTx film electrode exhibited excellent cyclic stability with the capacitance retention of 83 % after 7,000 consecutive charge-discharge cycles. Furthermore, flexible all solid-state symmetric V2CTx supercapacitor was assembled with the area capacitance of 23.4 µF⋅cm-2 at 5 mV⋅s-1. Inkjet printing technology reaches the combination of excellent photoelectric properties and high capacities of flexible V2CTx film electrodes, which provides a new strategy for manufacturing MXene film electrodes, broadening the application prospect of flexible energy storage devices.

SRSF2 is a key player in orchestrating the directional migration and differentiation of MyoD progenitors during skeletal muscle development.

SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.

Embryonic Genome Activation (EGA) Occurred at 1-Cell Stage of Embryonic Development in the Mud Crab, Scylla paramamosain, Revealed by RNA-Seq.

As a prerequisite for the success of embryo development, embryonic genome activation (EGA) is an important biological event in which zygotic gene products in the embryo are activated to replace maternal-derived transcripts. Although EGA has been extensively studied in a large number of vertebrates and invertebrates, there is a lack of information regarding this event in crustacean crab. In this study, the timing of EGA was confirmed by examining a transcriptomic dataset of early embryonic development, including mature oocytes and embryos through six early developmental stages, and signaling pathways associated with EGA were identified in the mud crab, S. paramamosain. The comprehensive transcriptomic data identified a total of 53,915 transcripts from these sequencing samples. Notable transcriptomic change was evident at the 1-cell stage, indicated by a 36% transcript number shift and a reduction in transcript fragment length, compared to those present in the mature oocytes. Concurrently, a substantial increase in the expression of newly transcribed transcripts was observed, with gene counts reaching 3485 at the 1-cell stage, indicative of the onset of EGA. GO functional enrichment revealed key biological processes initiated at the 1-cell stage, such as protein complex formation, protein metabolism, and various biosynthetic processes. KEGG analysis identified several critical signaling pathways activated during EGA, including the "cell cycle," "spliceosome," "RNA degradation", and "RNA polymerase", pathways. Furthermore, transcription factor families, including zinc finger, T-box, Nrf1, and Tub were predominantly enriched at the 1-cell stage, suggesting their pivotal roles in regulating embryonic development through the targeting of specific DNA sequences during the EGA process. This groundbreaking study not only addresses a significant knowledge gap regarding the developmental biology of S. paramamosain, especially for the understanding of the mechanism underlying EGA, but also provides scientific data crucial for the research on the individual synchronization of seed breeding within S. paramamosain aquaculture. Additionally, it serves as a reference basis for the study of early embryonic development in other crustacean species.

Plasmodium berghei TatD-like DNase hijacks host innate immunity by inhibiting the TLR9-NF-κB pathway.

Neutrophils and macrophages confine pathogens by entrapping them in extracellular traps (ETs) through activating TLR9 function. However, plasmodial parasites secreted TatD-like DNases (TatD) to counteract ETs-mediated immune clearance. We found that TLR9 mutant mice increased susceptibility to rodent malaria, suggesting TLR9 is a key protein for host defense. We found that the proportion of neutrophils and macrophages in response to plasmodial parasite infection in the TLR9 mutant mice was significantly reduced compared to that of the WT mice. Importantly, PbTatD can directly bind to the surface TLR9 (sTLR9) on macrophages, which blocking the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB, negatively regulated the signaling of ETs formation by both macrophages and neutrophils. Such, P. berghei TatD is a parasite virulence factor that can inhibit the proliferation of macrophages and neutrophils through directly binding to TLR9 receptors on the cell surface, thereby blocking the activation of the downstream MyD88-NF-kB pathways.

Viral myocarditis: From molecular mechanisms to therapeutic prospects.

Myocarditis is characterized as local or diffuse inflammatory lesions in the myocardium, primarily caused by viruses and other infections. It is a common cause of sudden cardiac death and dilated cardiomyopathy. In recent years, the global prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the widespread vaccination have coincided with a notable increase in the number of reported cases of myocarditis. In light of the potential threat that myocarditis poses to global public health, numerous studies have sought to elucidate the pathogenesis of this condition. However, despite these efforts, effective treatment strategies remain elusive. To collate the current research advances in myocarditis, and thereby provide possible directions for further research, this review summarizes the mechanisms involved in viral invasion of the organism and primarily focuses on how viruses trigger excessive inflammatory responses and in result in different types of cell death. Furthermore, this article outlines existing therapeutic approaches and potential therapeutic targets for the acute phase of myocarditis. In particular, immunomodulatory treatments are emphasized and suggested as the most extensively studied and clinically promising therapeutic options.

Prognostic Value of High-Density Lipoprotein Cholesterol in Patients with Overt Hepatic Encephalopathy.

Overt hepatic encephalopathy (OHE), a serious complication of liver cirrhosis, is associated with alterations in lipid and lipoprotein metabolism. We evaluated the correlation between high-density lipoprotein cholesterol (HDL-C) levels and transplant-free (TF) mortality in patients with OHE. Patients with OHE admitted to Beijing Ditan Hospital between January 2010 and August 2016 (n = 821) and between September 2016 and December 2020 (n = 480) were included in the training and validation sets, respectively. Independent predictors were explored by a multivariate Cox regression analysis, and the area under the receiver operating characteristic curve (AUC) was used to assess the prognostic value of these factors. The prognostic value of HDL-C was good (AUC at 1 year: 0.745) and was equivalent to that of the Model for End-Stage Liver Disease (MELD) score (AUC at 1 year: 0.788). The optimal threshold values for HDL-C and MELD were 0.5 mmol/L and 17, respectively. The 1-year TF mortality rates in the low-risk (HDL-C ≥ 0.5 mmol/L and MELD < 17) and high-risk (HDL-C < 0.5 mmol/L and MELD ≥ 17) groups were 7.5% and 51.5% in the training set and 10.1% and 48.2% in the validation set, respectively. HDL-C level < 0.5 mmol/L and MELD score > 17 can facilitate the identification of high-risk patients and provide a basis for timely treatment.

Depression and suicidal ideation among Chinese college students during the COVID-19 pandemic: the mediating roles of chronotype and sleep quality.

BACKGROUND: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . METHODS: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. RESULTS: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant. CONCLUSIONS: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality.

Multiple Stimulus Response Material Based on Sr-tcbpe MOF for Mechanochromism, Visualization Labeling, and Etching Toward TNP.

The abuse and excessive discharge of organic pollutants such as nitroaromatic compounds (NACs) have become a hot topic of concern for all humanity and society, and the development of fast, effective, and targeted technical means for detecting NACs also faces many challenges. Here, we reported a strontium-based metal-organic framework (MOF) {[Sr2(tcbpe)(H2O)4]}n (Sr-tcbpe), in which tcbpe represents deprotonated 4',4‴,4″‴,4‴‴-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'biphenyl]-4-carboxylic acid)). In Sr-tcbpe, Sr-O polyhedron and deprotonated tcbpe4- ligand have a staggered connection to form a self-assembled three-dimensional network structure. In addition, it is found that Sr-tcbpe undergoes no luminescent color change when grinding under solvent protection, while mechanochromic fluorescence behavior is observed when grinding directly, leading to luminescent color changes from cyan to green (Sr-tcbpe-G). Additionally, Sr-tcbpe and Sr-tcbpe-G could selectively detect PNP, DNP, and TNP, and Sr-tcbpe achieves visual fluorescence sensing detection toward TNP at a limit of detection as low as 2.25 µM. Moreover, during the detection process, unexpectedly, TNP exhibits a selective etching effect on Sr-tcbpe, which could drill nano holes with different sizes on the surface area of MOF materials to a certain extent, achieving the conversion of chemical energy to mechanical energy. In addition, the successful preparation of a portable sensor Sr-tcbpe@gypsum block provides a platform for the perfect combination of mechanochromic fluorescence behavior and visualization detection toward TNP. It lays the foundation for the practical application of MOF materials in daily life.

Invasion of human dental pulp fibroblasts by Porphyromonas gingivalis leads to autophagy via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling pathway.

OBJECTIVES: Porphyromonas gingivalis is a pathogenic bacterium that causes periodontitis and dental pulp infection. Autophagy is a potential mechanism involved in inflammatory disease. This study established an in vitro model of P. gingivalis intracellular infection in human dental pulp fibroblasts (HDPFs) to investigate the effects of live P. gingivalis on HDPFs. METHODS: Morphological and quantification techniques such as fluorescence microscopy, transmission electron microscopy (TEM), indirect immunofluorescence analysis, enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (PCR), and western blotting were used in this study. RESULTS: After cell invasion, P. gingivalis is mainly localized in the cytoplasm and lysosomes. Additionally, P. gingivalis activates autophagy in HDPFs by upregulating the expression of autophagy-related gene Beclin-1, activate autophagy-related gene12 (ATG12), and microtubule-associated protein light chain 3 (LC3). Furthermore, the invasion of P. gingivalis leads to increased phosphorylation of PI3K, Akt, and mTOR with the addition of rapamycin, whereas the addition of wortmannin decreased phosphorylation. This invasion of P. gingivalis, also causes an inflammatory response, leading to the upregulation of IL-1ß, IL-6, and TNF-α. Rapamycin helps decrease levels of pro-inflammatory cytokines, but the addition of wortmannin increases them. These results show that the invasion of P. gingivalis can cause excessive inflammation and promote the autophagy of HDPFs, which is regulated by PI3K/Akt/mTOR. CONCLUSIONS: P. gingivalis escapes the immune system by inducing autophagy in the host cells, causing excessive inflammation. P. gingivalis regulates autophagy in HDPFs through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway.

Effect of COVID-19 lockdowns on quality-of-life and health services access by socio-economic status in Australia.

This study examined changes in physical and mental health quality-of-life and health services access before and after the onset of the COVID-19 pandemic among individuals of lower and higher socio-economic status (SES) in Australia. Difference-in-differences and logistic regression models were undertaken using data from the Household, Income and Labour Dynamics in Australia (HILDA) survey and government data on COVID-19 lockdowns between January 2020 and February 2021. Individuals from higher SES reported larger decreases in mental health quality-of-life scores than those from lower SES after the onset of the pandemic. Those from lower SES reported less disruption with any health services (24.2% vs 30.4%; OR = 0.68; p < 0.001), specifically dental services (8.2% vs 15.4%; OR = 0.51; p < 0.001) and allied health services (5.9% vs 8.5%; OR = 0.60; p < 0.001), compared with those from higher SES. Additional days under lockdown were associated with reduced access to all health services (OR = 1.19). Furthermore, long-term health conditions (higher SES: OR = 1.54) and scores indicative of poorer physical (lower SES: OR = 1.17; higher SES: OR = 1.07) and mental health (lower SES: OR = 1.16; higher SES: OR = 1.12) were associated with increased health services disruption. While individuals from higher SES were more likely than those from lower SES to experience greater relative declines in mental health and increased disruption with health services access, individuals with a greater apparent need for health services, regardless of SES, may have faced inequalities in accessing these services during the COVID-19 pandemic.

Contribution of plant growth-promoting endophytic bacteria from hyperaccumulator to non-host plant zinc nutrition and health.

Application of microbial agents is a novel strategy to improve the quality and health of plant, which can be used to increase zinc (Zn) uptake and alleviate Zn toxicity. Here, endophytic bacteria with Zn solubilizing and growth-promoting properties were isolated from hyperaccumulating ecotype (HE) of Sedum alfredii Hance and their effects on Zn absorption and accumulation of non-hyperaccumulating ecotype (NHE) were studied. The results showed that most endophytic bacteria of HE have good Zn solubilizing or growth-promoting properties. Under the condition of 20 µM ZnSO4, the biomass of NHE inoculated with SaPS1, SaEN2, SaPR2, SaBA2, SaBA3 was 2.8-3.2 times higher than that of non-inoculation control, and the Zn concentration of shoots was increased by 45.9, 89.0, 53.7, 77.5, and 42.6% after inoculation with SaPA1, SaP1, SaEN2, SaBA1, and SaBA2. Under the condition of 100 µM ZnSO4, inoculation with SaVA1, SaPS3, SaB1, SaPR1, and SaEN3 alleviated Zn stress and significantly reduced Zn concentration of shoots. Therefore, endophytic bacteria can be an effective means of improving plant Zn nutrition quality in the normal condition and benefit plant health in the stress environment.

In this study, endophytes with Zn solubilizing properties were systematically isolated from Zn hyperaccumulator Sedum alfredii Hance. The aim is to identify endophyte resources with good promoting effect on plant growth and Zn uptake, and to provide scientific basis for the development of efficient biofortified agent.