TAT-beclin1 treatment accelerates the development of atherosclerotic lesions in ApoE-deficient mice.

The importance of autophagy in atherosclerosis has garnered significant attention regarding the potential applications of autophagy inducers. However, the impact of TAT-Beclin1, a peptide inducer of autophagy, on the development of atherosclerotic plaques remains unclear. Single-cell omics analysis indicates a notable reduction in GAPR1 levels within fibroblasts, stromal cells, and macrophages during atherosclerosis. Tat-beclin1 (T-B), an autophagy-inducing peptide derived from Beclin1, could selectively bind to GAPR1, relieving its inhibition on Beclin1 and thereby augmenting autophagosome formation. To investigate its impact on atherosclerosic plaque progression, we established the ApoE-/- mouse model of carotid atherosclerotic plaques. Surprisingly, intravenous administration of Tat-beclin1 dramatically accelerated the development of carotid artery plaques. Immunofluorescence analysis suggested that macrophage aggregation and autophagosome formation within atherosclerotic plaques were significantly increased upon T-B treatment. However, immunofluorescence and transmission electron microscopy (TEM) analysis revealed a reduction in autophagy flux through lysosomes. In vitro, the interaction between T-B and GAPR1 was confirmed in RAW264.7 cells, resulting in the increased accumulation of p62/SQSTM1 and LC3-II in the presence of ox-LDL. Additionally, T-B treatment elevated the protein levels of p62/SQSTM1, LC3-II, and cleaved caspase 1, along with the secretion of IL-1ß in response to ox-LDL exposure. In summary, our study underscores that T-B treatment amplifies abnormal autophagy and inflammation, consequently exacerbating atherosclerotic plaque development in ApoE-/- mice.

Associations between Sarcopenia and trajectories of activities of daily living disability: a nationwide longitudinal study of middle-aged and older adults in China from 2011 to 2018.

BACKGROUND: Sarcopenia is an age-related clinical syndrome, which is associated with numerous adverse outcomes among older adults. The relationship between sarcopenia and activities of daily living (ADL) disability has been studied in China, but these findings usually focused on a single time point. The patterns of ADL can change over time and vary among individuals. Therefore, it is necessary to explore the association between sarcopenia and trajectories of ADL disability. METHODS: According to Asian Working Group for Sarcopenia (AWGS) 2019 criteria, muscle mass, muscle strength, and physical performance measurements were measured to diagnose sarcopenia. A six-item ADL score was used to measure ADL disability, and trajectories of ADL disability were identified by the latent class trajectory modelling (LCTM). Multiple logistic regression models were performed to examine the association between sarcopenia and trajectories of ADL disability. RESULTS: Among 9113 middle-aged and older adults, three trajectories of ADL disability were determined according to changes in ADL score during follow-up, including a mild-high trajectory (n = 648, 7.11%), followed by the low-mild trajectory (n = 3120, 34.24%) and low-low trajectory (n = 5345, 58.65%). After adjustment for covariates, severe sarcopenia was significantly associated with higher risks of being in the mild-high trajectory group (OR = 3.31, 95%CI: 2.10-5.22) and the low-mild trajectory group (OR = 1.44, 95%CI: 1.05-1.98), compared with the low-low trajectory group. This association was still observed when stratified by age and gender. In addition, participants with sarcopenic obesity were associated with a higher risk of ADL disability (OR = 3.99; 95% CI: 2.50-6.09). CONCLUSIONS: Among the middle-aged and older Chinese adults, sarcopenia and sarcopenic obesity were both associated with persistent higher trajectories of ADL disability. It suggested that early interventions to sarcopenia and sarcopenic obesity among the middle-aged and older adults may reduce the progression of ADL disability.

Programmable DNA Scaffolds Enable Orthogonal Engineering of Cell Membrane-Based Nanovesicles for Therapeutic Development.

Cell membrane-based nanovesicles (CMNVs) play pivotal roles in biomolecular transportation in living organisms and appear as attractive bioinformed nanomaterials for theranostic applications. However, the current surface-engineering technologies are limited in flexibility and orthogonality, making it challenging to simultaneously display multiple different ligands on the CMNV surface in a precisely controlled manner. Here, we developed a DNA scaffold-programmed approach to orthogonally engineer CMNVs with versatile ligands. The designed DNA scaffolds can rapidly anchor onto the CMNV surface, and their unique sequences and hybridized properties enable independent control of the loading of multiple different types of biomolecules on the CMNVs. As a result, the orthogonal engineering of CMNVs with a renal targeted peptide and a therapeutic protein at controlled ratios demonstrated an enhanced renal targeting and repair potential in vivo. This study highlights that a DNA scaffold-programmed platform can provide a potent means for orthogonal and flexible surface engineering of CMNVs for diverse therapeutic purposes.

Lunar Regolith Geopolymer Concrete for In-Situ Construction of Lunar Bases: A Review.

The construction of lunar bases represents a fundamental challenge for deep space exploration, lunar research, and the exploitation of lunar resources. In-situ resource utilization (ISRU) technology constitutes a pivotal tool for constructing lunar bases. Using lunar regolith to create geopolymers as construction materials offers multiple advantages as an ISRU technique. This paper discusses the principle of geopolymer for lunar regolith, focusing on the reaction principle of geopolymer. It also analyzes the applicability of geopolymer under the effects of the lunar surface environment and the differences between the highland and mare lunar regolith. This paper summarizes the characteristics of existing lunar regolith simulants and the research on the mechanical properties of lunar regolith geopolymers using lunar regolith simulants. Highland lunar regolith samples contain approximately 36% amorphous substances, the content of silicon is approximately 28%, and the ratios of Si/Al and Si/Ca are approximately 1.5 and 2.6, respectively. They are more suitable as precursor materials for geopolymers than mare samples. The compressive strength of lunar regolith geopolymer is mainly in the range of 18~30 MPa. Sodium silicate is the most commonly utilized activator for lunar regolith geopolymers; alkalinity in the range of 7% to 10% and modulus in the range of 0.8 to 2.0 are suitable. A vacuum environment and multiple temperature cycles reduce the mechanical properties of geopolymers by 8% to 70%. Future research should be concentrated on the precision control of the lunar regolith's chemical properties and the alkali activation efficacy of geopolymers in the lunar environment.

Associations of computer gaming with incident dementia, cognitive functions, and brain structure: a prospective cohort study and Mendelian randomization analysis.

BACKGROUND: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. METHODS: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. RESULTS: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). CONCLUSIONS: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.

Association between remnant cholesterol and the risk of cardiovascular disease in Chinese population.

OBJECTIVES: Previous genetic, observational, and clinical intervention studies reported that circulating levels of remnant cholesterol was associated with cardiovascular disease (CVD). However, whether remnant cholesterol can predict CVD events in Chinese population was not well characterized. STUDY DESIGN: This was a prospective cohort study. METHODS: We used the data of 9456 Chinese adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS). Estimated remnant cholesterol was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. Cox proportional hazard models and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and CVD, stroke and cardiac events. RESULTS: During 7 years of follow-up, a total of 886 (9.37 %) respondents experienced CVD, 392 (4.15 %) experienced stroke and 544 (5.75 %) experienced cardiac events. In multivariable-adjusted analyses, the adjusted hazard ratios (95 % confidence interval) for the highest versus lowest quartile of remnant cholesterol were 1.14 (1.02-1.32) for CVD and 1.43 (1.12-1.82) for stroke, and each 1-SD increase of log-transformed remnant cholesterol (2.93 mg/dl) was associated with 5 % and 11 % increased risk of the CVD and stroke, respectively. Remnant cholesterol was not associated with increased risk of cardiac events. CONCLUSION: Elevated remnant cholesterol levels were positively associated with CVD and stroke in Chinese adult population, suggesting that remnant cholesterol could be considered as a preferential predictor and treatment target of CVD in Chinese population.

Association of estimated cardiorespiratory fitness in middle-aged and elderly people with cardiovascular disease: Evidence from the China health and retirement longitudinal study.

BACKGROUND AND AIM: Cardiovascular diseases (CVD) is a major threat to public health, while cardiorespiratory fitness (CRF) is a key predictor of chronic disease. Given this, the purpose of this study was to investigate the relationship between estimated CRF (eCRF) and CVD in middle-aged and elderly Chinese people. METHODS AND RESULTS: The China Health and Retirement Longitudinal Study (CHARLS) with 4761 individuals were included in analysis. Participants were divided into three groups according to eCRF quantile in sex subgroups. Cox proportional hazards regression models were used to explore the correlation of eCRF with CVD (stroke or cardiac events). In total, 4761 participants were included in this cohort study (2500 [52.51%] women). During a 7-year follow-up from 2011 to 2018, 796 CVDs (268 Strokes and 588 cardiac events) were recorded. In multivariable-adjusted analyses, for per 1 SD increase of eCRF, the age-adjusted risk of CVD was reduced by about 18% (HR = 0.82; 95% CI, 0.72-0.93) in men, and was reduced by about 29% (HR = 0.71; 95% CI, 0.62-0.81) in women. Similar associations were also found between eCRF and stroke and cardiac events. Both subgroup and interaction analyses showed that the interaction of age had a statistically significant effect on CVD risk. CONCLUSION: ECRF was inversely associated with CVD risk (stroke or cardiac events) in both men and women. Remarkable sex and age differences exist in the effectiveness of increasing eCRF to reduce the risk of CVD. As a potential, efficient and cost-effective risk prediction tool, eCRF deserves further attention and wide application.

Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Physical Activity, Sleep, and Risk of Late-Onset Severe Mental Illness: A Prospective Cohort Study From UK Biobank.

BACKGROUND AND HYPOTHESIS: Previous studies have found that both physical inactivity and poor sleep are deleteriously associated with severe mental illness (SMI). The aim of current study was to investigate the joint association of physical activity (PA) and sleep with late-onset SMI (schizophrenia and bipolar disorder) risk. STUDY DESIGN: A total of 340 187 (for schizophrenia)/340 239 (for bipolar disorder) participants without schizophrenia or bipolar disorder from the UK Biobank were included. Baseline PA levels were categorized as high, intermediate, and low according to the total volume of PA. Sleep was categorized into healthy, intermediate, and poor according to an established composited sleep score of chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. We derived 9 PA-sleep combinations, accordingly. STUDY RESULTS: After an average follow-up of 13.2 years, 814 participants experienced schizophrenia and 846 participants experienced bipolar disorder. Both low PA level, intermediate, and poor sleep were independently associated with increased risk of SMI. PA level and sleep had additive and multiplicative interactions on SMI risk. Compared to those with high PA level and healthy sleep, individuals with low PA and poor sleep had the highest risk of SMI (hazard ratio: 1.95; 95% CI: 1.02-3.70, P < .001) for schizophrenia; (hazard ratio: 3.81; 95% CI: 2.35-6.15) for bipolar disorder. A higher PA level may attenuate the detrimental effects of poor sleep. CONCLUSION: Both low PA and poor sleep was associated with increasing risk of late-onset SMI. Those with low PA and poor sleep had the highest risk of late-onset SMI, suggesting likely synergistic effects. Our findings supported the need to target both PA and sleep behaviors in research and clinical practice.

The mechanism of action of Botrychium (Thunb.) Sw. for prevention of idiopathic pulmonary fibrosis based on 1H-NMR-based metabolomics.

OBJECTIVES: This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on bleomycin-induced IPF rats. METHODS: The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis. KEY FINDINGS: Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-ß1 in the pulmonary tissue. Secondly, Masson's trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies. CONCLUSIONS: Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent.

Chronic inhalation of H2S in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats.

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Appropriate glycemic management protects the germline but not the uterine environment in hyperglycemia.

Emerging evidence indicates that parental diseases can impact the health of subsequent generations through epigenetic inheritance. Recently, it was shown that maternal diabetes alters the metaphase II oocyte transcriptome, causing metabolic dysfunction in offspring. However, type 1 diabetes (T1D) mouse models frequently utilized in previous studies may be subject to several confounding factors due to severe hyperglycemia. This limits clinical translatability given improvements in glycemic control for T1D subjects. Here, we optimize a T1D mouse model to investigate the effects of appropriately managed maternal glycemic levels on oocytes and intrauterine development. We show that diabetic mice with appropriate glycemic control exhibit better long-term health, including maintenance of the oocyte transcriptome and chromatin accessibility. We further show that human oocytes undergoing in vitro maturation challenged with mildly increased levels of glucose, reflecting appropriate glycemic management, also retain their transcriptome. However, fetal growth and placental function are affected in mice despite appropriate glycemic control, suggesting the uterine environment rather than the germline as a pathological factor in developmental programming in appropriately managed diabetes.

Hypertension combined with limitations in activities of daily living and the risk for cardiovascular disease.

OBJECTIVE: The aim of present study was to evaluate the combined effect of hypertension and activities of daily living (ADL)/instrumental activities of daily living (IADL) with the risk of CVD, stroke and cardiac events. METHODS: A total of 14,083 participants aged 45 years or older from the China Health and Retirement longitudinal study were included in current study. Participants were divided into 4 groups according to hypertension and ADL/IADL status. Cox proportional hazards regression model was used to explore the associations between hypertension, ADL/IADL and new-onset CVD, stroke and cardiac events. RESULTS: During the 7-year follow-up, a total of 2,324 respondents experienced CVD (including 783 stroke and 1,740 cardiac events). Individuals with limitations in ADL alone, or with hypertension alone, or with both limitations in ADL and hypertension were associated with increased risk of CVD, with the adjusted hazard ratios (95% confidence intervals) were 1.17(1.00-1.35), 1.36(1.24-1.49) and 1.44(1.23-1.68), respectively. Those with limitations in ADL and hypertension also had higher risk of stroke (hazard ratios = 1.64; 1.26-2.14) and cardiac events (hazard ratios = 1.37; 1.14-1.64). Similarly, individuals with both limitations in IADL and hypertension were associated with increased risk of CVD (hazard ratios = 1.34; 1.15-1.57), stroke (hazard ratios = 1.50; 1.17-1.95) and cardiac events (hazard ratios = 1.27; 1.06-1.53). CONCLUSION: Hypertension and limitations in ADL/IADL jointly increased the risk of CVD, stroke and cardiac events.

Enhancing the stability of mung bean-based milk: Insights from protein characteristics and raw material selection.

Plant-based milk (PBM) alternatives are gaining popularity worldwide as the change of consumers' nutritional habits and health attitudes. Mung beans, recognized for their nutritional value, have gained attention as potential ingredients for PBM. Nevertheless, mung bean-based milk (MBM) faces instability issues common to other plant-based milks. This study investigated the factors influencing MBM stability focusing on raw materials. We selected 6 out of 20 varieties based on their MBM centrifugation sedimentation rates, representing both stable and unstable MBM. Stable MBM exhibited distinct advantages, including reduced separation rate, smaller particle size, lower viscosity, fewer protein aggregates, higher soluble protein content, and increased consumer acceptance. Major nutritional components such as protein, starch, and lipids were not significant different between stable and unstable MBM varieties. The pivotal distinction may lay in the protein properties and composition. Stable MBM varieties exhibited significantly improved protein solubility and emulsion stability, along with elevated concentrations of legume-like acidic subunits, basic 7S proteins, and 28 kDa and 26 kDa vicilin-like subunits. The increasement of these proteins likely contributed to the improvement in protein characteristics that affect MBM stability. These findings offer valuable insights for raw material selection and guidance for future mung bean breeding to enhance mung bean milk production.

Associations between sarcopenic obesity and risk of cardiovascular disease: A population-based cohort study among middle-aged and older adults using the CHARLS.

BACKGROUND: Previous studies have demonstrated that sarcopenia was associated with a high risk of cardiovascular disease (CVD). Nevertheless, little is known about the associations between sarcopenic obesity/possibly sarcopenic obesity and the risk of CVD among senior and middle-aged adults. METHODS: Utilizing the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), a sum of 7703 individuals aged at least 45 years were divided into four groups. The effects of sarcopenic obesity and possibly sarcopenic obesity on CVD were calculated using Cox proportional hazards regression models. Non-sarcopenic participants with optimal body mass index (BMI) or waist circumference (WC) served as a control group. RESULTS: Sarcopenic obesity were related to increased risks of CVD (HR = 1.39; 95% CI = 1.16-1.67), heart disease (HR = 1.36; 95% CI = 1.10-1.67) and stroke (HR = 1.40; 95% CI = 1.02-1.92) compared with the optimal reference group. Similarly, the risk of CVD, heart disease and stroke increased by 0.34, 0.28 and 0.39 times in obese people with possible sarcopenia compared to the control group. Sensitivity analysis identified similar results to those described above. Patients with sarcopenia and a BMI ≥28.0 kg/m2 had a 1.47- and 1.48-fold risk of developing CVD and heart disease than controls. CONCLUSION: Sarcopenic obesity and possibly sarcopenic obesity are positively associated with the development of CVD. The middle-aged and elderly population should prevent obesity and maintain muscle mass through some interventions such as weight control and moderate exercise, which may reduce the CVD risk.

Effect of Laryngopharyngeal Reflux and Potassium-Competitive Acid Blocker (P-CAB) on the Microbiological Comprise of the Laryngopharynx.

OBJECTIVE: To probe the microbiota composition progressing from healthy individuals to those with laryngopharyngeal reflux disease (LPRD) and subsequently undergoing potassium-competitive acid inhibitor (P-CAB) therapy. STUDY DESIGN: Prospective case-control study. SETTING: Academic Medical Center. METHODS: Forty patients with LPRD and 51 patients without LPRD were recruited. An 8-week P-CAB therapy was initiated (post-T-LPRD), and 39 had return visits. In total, 130 laryngopharyngeal saliva samples were collected and sequenced by targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene using an Illumina MiSeq. Amplicon sequence variants (ASVs) and clinical indices were analyzed. RESULTS: Alpha and beta diversities were compared among the non-LPRD, LPRD, and post-T-LPRD groups, and the Observed_ASVs were not significantly different. At the same time, the Shannon and Simpson indices, unweighted Unifrac, weighted Unifrac, and binary Jaccard distance were significantly different between non-LPRD and LPRD groups. In addition, significant differences were found in the abundance of Streptococcus, Prevotella, and Prevotellaceae in the LPRD versus non-LPRD groups, and Neisseria, Leptotrichia, and Allprevotella in the LPRD versus post-T-LPRD groups. The genera model was used to distinguish patients with LPRD from those without, and a better receiver operating characteristic curve was formed after combining the clinical indices of reflux symptom index, reflux finding score, and pepsin, with an area under the curve of 0.960. CONCLUSION: Laryngopharyngeal microbial communities changed after laryngopharyngeal reflux and were modified further after P-CAB treatment, which provides a potential diagnostic value for LPRD, especially when combined with clinical indices.

Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target.

Hormetic effect of a short-chain PFBS on Microcystis aeruginosa and its molecular mechanism.

Short-chain Perfluorinated compounds (PFCs), used as substitutes for highly toxic long-chain PFCs, are increasingly entering the aquatic environment. However, the toxicity of short-chain PFCs in the environment is still controversial. This study investigated the effects of short-chain perfluorobutanesulfonic acid (PFBS) at different concentrations (2.5, 6, 14.4, 36, and 90 mg/L) on M. aeruginosa growth under 12-day exposure and explored the molecular mechanism of toxicity using transcriptomics. The results showed that M. aeruginosa exhibited hormetic effects after exposure to PFBS. Low PFBS concentrations stimulated algal growth, whereas high PFBS concentrations inhibited it, and this inhibitory effect became progressively more pronounced with increasing PFBS exposure concentrations. Transcriptomics showed that PFBS promoted the pathways of photosynthesis, glycolysis, energy metabolism and peptidoglycan synthesis, providing the energy required for cell growth and maintaining cellular morphology. PFBS, on the other hand, caused growth inhibition in algae mainly through oxidative stress, streptomycin synthesis, and genetic damage. Our findings provide new insights into the toxicity and underlying mechanism of short-chain PFCs on algae and inform the understanding of the hormetic effect of short-chain PFCs, which are crucial for assessing their ecological risks in aquatic environments.