Timing offset calibration for TOF PET using stationary line source scans at multiple positions.

Background. Accurate timing offset calibration is crucial for time-of-flight (TOF) positron emission tomography (PET) to mitigate image artifacts and improve quantitative accuracy. However, existing methods are often time-consuming, complex, or costly.Objective. This paper presents a method for TOF PET timing offset calibration that eliminates the need for costly equipment, phantoms, short-half-life sources, and precise source positioning.Approach. We estimate channel timing offsets using stationary scans of a68Ge line source, typically used for routine quality control, at a minimum of three non-coplanar positions, with each position scanned for two minutes. The line source positions are determined accurately from reconstructed images using a simple algorithm, allowing precise calculation of arrival time differences. Channel timing offsets are estimated by solving a least squares problem. This method is assessed through analyses of phantoms and patient images using a RAYSOLUTION DigitMI 930 scanner.Main results. The estimated timing offsets ranged from -500 ps to 500 ps across all channels. Calibration with a minimum of three scanned positions was sufficient to correct these offsets, achieving less than a 1% discrepancy across various metrics of the image quality (IQ) phantom compared to 12 positions. This calibration significantly reduced edge artifacts in TOF reconstruction of both phantoms and patients. Furthermore, the IQ phantom displayed a 13% increase in average contrast recovery (CR), a 68% reduction in average background variability (BV) across all spheres, and an 80% reduction in average residual error. Consistent with the phantom results, patient data revealed enhancements in maximum standardized uptake values (SUVmax) from 14% to 55% for lesions measuring 6 mm to 14 mm. The calibration also improved lesion-to-background contrast and eliminated artifacts caused by the spillover effect of the kidneys and bladder.Significance. The proposed method is fast, user-friendly, and cost-effective, effectively improving lesion detection and diagnostic accuracy.

Disturbed glucose homeostasis and its increased allostatic load in response to individual, joint and fluctuating air pollutants exposure: Evidence from a longitudinal study in prediabetes.

We investigated the effect of individual, joint and fluctuating exposure to air pollution (PM2.5, BC, NO3-, NH4+, OM, SO42-, PM10, NO2, SO2, O3) on glucose metabolisms among prediabetes, and simultaneously explored the modifying effect of lifestyle. We conducted a longitudinal study among prediabetes during 2018-2022. Exposure windows within 60-days moving averages and their variabilities were calculated. FBG, insulin, HOMA-IR, HOMA-B, triglyceride glucose index (TyG), glucose insulin ratio (GI) and allostatic load of glucose homeostasis system (AL-GHS) was included. Linear mixed-effects model and BKMR were adopted to investigate the individual and overall effects, respectively. We also explored the preventive role of lifestyle. Individual air pollutant was associated with increased FBG, insulin, HOMA-IR, HOMA-B, TyG, and decreased GI. People with FBG ≥6.1 mmol/L were more susceptible. Air pollutants mixture were only associated with increased HOMA-B, and constituents have the highest group-PIP. Air pollutants variation also exert harmful effect. We observed similar diabetic effect on AL-GHS. Finally, the diabetic effect of air pollutants disappeared if participants adopt a favorable lifestyle. Our findings highlighted the importance of comprehensively assessing multiple air pollutants and their variations, focusing on metabolic health status in the early prevention of T2D, and adopting healthy lifestyle to mitigate such harmful effect.

Pembrolizumab therapy in a patient with NSCLC and bullous pemphigoid: A case report.

Immune checkpoint inhibitor (ICI) therapy, which targets programmed cell death protein 1, has demonstrated enhanced survival outcomes in numerous patients with cancer. Historically, individuals with autoimmune diseases have been excluded from clinical trials involving cancer immunotherapies due to concerns about the potential worsening of their underlying autoimmune conditions. In the present case report, a patient with non-small cell lung cancer and bullous pemphigoid (BP) who underwent treatment with the ICI pembrolizumab is described. In this specific clinical case, no severe exacerbation of the underlying autoimmune disease was observed. Contrarily, the patient not only tolerated pembrolizumab well but also experienced amelioration of the BP lesions after the treatment. This case challenges the conventional exclusion criteria for ICI therapy in patients with autoimmune diseases, suggesting the potential safety and efficacy of such treatments in this specific population. However, further investigations and larger-scale studies are warranted to validate these findings and provide a more comprehensive understanding of the implications of ICI therapy in patients with autoimmune comorbidities.

Continuous Positive Airway Pressure Treatment and Hypertensive Adverse Outcomes in Pregnancy: A Systematic Review and Meta-Analysis.

Importance: Pregnancy may contribute to the development or exacerbation of obstructive sleep apnea (OSA) and increase the risk of gestational complications. Continuous positive airway pressure (CPAP) is the first-line and criterion standard treatment for OSA and is regarded as the most feasible choice during pregnancy. However, the association between CPAP therapy in pregnant women with OSA and reduced gestational complications remains inconclusive. Objective: To investigate the association between CPAP therapy in pregnant women with OSA and the reduction of adverse hypertensive outcomes during gestation. Data Sources: Keyword searches of PubMed, Embase, and the Cochrane Database of Systematic Reviews and Clinical Trials were conducted from inception to November 5, 2023. Study Selection: Original studies reporting the treatment effect of CPAP use on lowering hypertension and preeclampsia risks in pregnant women with OSA were selected. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed in the reporting of reviews. Data were independently extracted by 2 authors. Random-effects model meta-analyses were performed and risk ratios (RRs) reported. Subgroup analysis, meta-regression based on age and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and publication bias assessment were also conducted. Main Outcome and Measures: The primary outcome was the RR of gestational hypertension and preeclampsia between pregnant women with OSA receiving CPAP treatment and those who did not receive CPAP treatment. Results: Six original studies in 809 participants (mean age, 31.4 years; mean BMI, 34.0) were identified and systematically reviewed for meta-analysis. The pooled results showed significant differences between the intervention (CPAP use) and the control (non-CPAP use) groups in reducing the risk of gestational hypertension (RR, 0.65; 95% CI, 0.47-0.89; P = .008) and preeclampsia (RR, 0.70; 95% CI, 0.50-0.98; P = .04). Meta-regression revealed that patients' age (coefficient, -0.0190; P = .83) and BMI (coefficient, -0.0042; P = .87) were not correlated with reduction of risk of hypertension and preeclampsia. Conclusions and Relevance: These findings suggest that implementing CPAP treatment in pregnant women with OSA may reduce the risk of gestational hypertension and preeclampsia.

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus.

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 µm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 µg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

Prognostic impact of bridge or neoadjuvant induction chemotherapy in patients with resected oral cavity cancer: A nationwide cohort study.

BACKGROUND: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. METHODS: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV. RESULTS: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05). CONCLUSIONS: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment.

The optimal measurement period of actigraphy for circadian rhythm in relation to adiposity: A retrospective case-control study.

BACKGROUND: This study focused on the relationship between adiposity and Rest-Activity Rhythms (RAR), utilizing both parametric cosine-based models and non-parametric algorithms. The emphasis was on the impact of varying measurement periods (7-28 days) on this relationship. METHODS: We retrieved actigraphy data from two datasets, encompassing a diverse cohort recruited from an obesity outpatient clinic and a workplace health promotion program. Participants were required to wear a research-grade wrist actigraphy device continuously for a minimum of four weeks. The final dataset included 115 individuals (mean age 40.7 ± 9.5 years, 51 % female). We employed both parametric and non-parametric methods to quantify RAR using six standard variables. Additionally, the study evaluated the correlations between three key adiposity indices - Body Mass Index (BMI), Visceral Adipose Tissue (VAT) area, and Body Fat Percentage (BF%) - and circadian rhythm indicators, controlling for factors like physical activity, age, and gender. RESULTS: The obesity group displayed a significantly lower relative amplitude (RA) as per non-parametric algorithm findings, with a decreased amplitude noted in the parametric algorithm analysis, in comparison to the overweight and control groups. The relationship between circadian rhythm indicators and adiposity metrics over 7- to 28-day periods was examined. A notable negative correlation was observed between RA and both BMI and VAT, while correlation coefficients between adiposity indicators and non-parametric circadian parameters increased with extended durations of actigraphy data. Specifically, RA over a 28-day period was significantly correlated with BF%, a trend not seen in the 7-day measurement (p = 0.094) in multivariate linear regression. The strength of the correlation between BF% and 28-day RA was more pronounced than that in the 7-day period (p = 0.044). However, replacing RA with amplitude as per parametric cosinor fitting yielded no significant correlations for any of the measurement periods. CONCLUSION: The study concludes that a 28-day measurement period more effectively captures the link between disrupted circadian rhythms and adiposity. Non-parametric algorithms, in particular, were more effective in characterizing disrupted circadian rhythms, especially when extending the measurement period beyond the standard 7 days.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

Predicting negative attitudes towards suicide in social media texts: prediction model development and validation study.

Background: Implementing machine learning prediction of negative attitudes towards suicide may improve health outcomes. However, in previous studies, varied forms of negative attitudes were not adequately considered, and developed models lacked rigorous external validation. By analyzing a large-scale social media dataset (Sina Weibo), this paper aims to fully cover varied forms of negative attitudes and develop a classification model for predicting negative attitudes as a whole, and then to externally validate its performance on population and individual levels. Methods: 938,866 Weibo posts with relevant keywords were downloaded, including 737,849 posts updated between 2009 and 2014 (2009-2014 dataset), and 201,017 posts updated between 2015 and 2020 (2015-2020 dataset). (1) For model development, based on 10,000 randomly selected posts from 2009 to 2014 dataset, a human-based content analysis was performed to manually determine labels of each post (non-negative or negative attitudes). Then, a computer-based content analysis was conducted to automatically extract psycholinguistic features from each of the same 10,000 posts. Finally, a classification model for predicting negative attitudes was developed on selected features. (2) For model validation, on the population level, the developed model was implemented on remaining 727,849 posts from 2009 to 2014 dataset, and was externally validated by comparing proportions of negative attitudes between predicted and human-coded results. Besides, on the individual level, similar analyses were performed on 300 randomly selected posts from 2015 to 2020 dataset, and the developed model was externally validated by comparing labels of each post between predicted and actual results. Results: For model development, the F1 and area under ROC curve (AUC) values reached 0.93 and 0.97. For model validation, on the population level, significant differences but very small effect sizes were observed for the whole sample (χ 2 1 = 32.35, p < 0.001; Cramer's V = 0.007, p < 0.001), men (χ 2 1 = 9.48, p = 0.002; Cramer's V = 0.005, p = 0.002), and women (χ 2 1 = 25.34, p < 0.001; Cramer's V = 0.009, p < 0.001). Besides, on the individual level, the F1 and AUC values reached 0.76 and 0.74. Conclusion: This study demonstrates the efficiency and necessity of machine learning prediction of negative attitudes as a whole, and confirms that external validation is essential before implementing prediction models into practice.

Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer.

BACKGROUND: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). METHODS: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. FINDINGS: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceaebacterium and Blautiawexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. CONCLUSIONS: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. FUNDING: This research was funded by the China National Natural Science Foundation (82202884).

Dynamic multicolour tuning in π-conjugated polymers towards flexible electrochromic displays.

Multicolour electrochromic materials have been considered as a promising alternative to achieve dynamic full-colour tuning towards next-generation electronic display technology. However, the development of electrochromics with wide colour gamut and subtle multicolour tunability still remains challenging due to inflexible energy level structures in intrinsic active materials. Herein, the electrochromic π-conjugated polymers with rich and subtle colour tunability were designed and developed based on a fine adjustment on the energy level structures. The chromatic transition covers almost full-colour gamut, and each colour scheme has a rich variety of categories stemming from versatile hues, chromas and lightnesses. Moreover, the multicolour π-conjugated polymers also demonstrate superior overall electrochromic performance, including fast switching (∼1.0 s), high colouration efficiency (160.4 cm2 C-1@550 nm) and good reversibility (over 90 % retention after 10,000 cycles). As a proof of concept, ultrathin and flexible prototype devices are developed by utilizing the multicolour π-conjugated polymers as electrochromic active layer, exhibiting a wide colour gamut and highly saturated multicolour tunability. The design principles proposed in this work may also be applicable to diverse optoelectronic applications.

Racial and Ethnic Disparity for Cancer Mortality in General and Single-Payer Healthcare Systems in the United States.

BACKGROUND: It remains unclear what factors significantly drive racial disparity in cancer survival in the United States (US). We compared adjusted mortality outcomes in cancer patients from different racial and ethnic groups on a population level in the US and a single-payer healthcare system. PATIENTS AND METHODS: We selected adult patients with incident solid and hematologic malignancies from the Surveillance, Epidemiology, and End Results (SEER) 2011-2020 and Veteran Affairs national healthcare system (VA) 2011-2021. We classified the self-reported NIH race and ethnicity into non-Hispanic White (NHW), non-Hispanic Black (NHB), non-Hispanic Asian Pacific Islander (API), and Hispanic. Cox regression models for hazard ratio of racial and ethnic groups were built after adjusting confounders in each cohort. RESULTS: The study included 3,104,657 patients from SEER and 287,619 patients from VA. There were notable differences in baseline characteristics in the two cohorts. In SEER, adjusted HR for mortality was 1.12 (95% CI, 1.12-1.13), 1.03 (95% CI, 1.03-1.04), and 0.91 (95% CI, 0.90-0.92), for NHB, Hispanic, and API patients, respectively, vs. NHW. In VA, adjusted HR was 0.94 (95% CI, 0.92-0.95), 0.84 (95% CI, 0.82-0.87), and 0.96 (95% CI, 0.93-1.00) for NHB, Hispanic, and API, respectively, vs. NHW. Additional subgroup analyses by cancer types, age, and sex did not significantly change these associations. CONCLUSIONS: Racial disparity continues to persist on a population level in the US especially for NHB vs. NHW patients, where the adjusted mortality was 12% higher in the general population but 6% lower in the single-payer VA system.

Comparative analysis of gut microbiota in children with obstructive sleep apnea: assessing the efficacy of 16S rRNA gene sequencing in metabolic function prediction based on weight status.

Background: Analyzing bacterial microbiomes consistently using next-generation sequencing (NGS) is challenging due to the diversity of synthetic platforms for 16S rRNA genes and their analytical pipelines. This study compares the efficacy of full-length (V1-V9 hypervariable regions) and partial-length (V3-V4 hypervariable regions) sequencing of synthetic 16S rRNA genes from human gut microbiomes, with a focus on childhood obesity. Methods: In this observational and comparative study, we explored the differences between these two sequencing methods in taxonomic categorization and weight status prediction among twelve children with obstructive sleep apnea. Results: The full-length NGS method by Pacbio® identified 118 genera and 248 species in the V1-V9 regions, all with a 0% unclassified rate. In contrast, the partial-length NGS method by Illumina® detected 142 genera (with a 39% unclassified rate) and 6 species (with a 99% unclassified rate) in the V3-V4 regions. These approaches showed marked differences in gut microbiome composition and functional predictions. The full-length method distinguished between obese and non-obese children using the Firmicutes/Bacteroidetes ratio, a known obesity marker (p = 0.046), whereas the partial-length method was less conclusive (p = 0.075). Additionally, out of 73 metabolic pathways identified through full-length sequencing, 35 (48%) were associated with level 1 metabolism, compared to 28 of 61 pathways (46%) identified through the partial-length method. The full-length NGS also highlighted complex associations between body mass index z-score, three bacterial species (Bacteroides ovatus, Bifidobacterium pseudocatenulatum, and Streptococcus parasanguinis ATCC 15912), and 17 metabolic pathways. Both sequencing techniques revealed relationships between gut microbiota composition and OSA-related parameters, with full-length sequencing offering more comprehensive insights into associated metabolic pathways than the V3-V4 technique. Conclusion: These findings highlight disparities in NGS-based assessments, emphasizing the value of full-length NGS with amplicon sequence variant analysis for clinical gut microbiome research. They underscore the importance of considering methodological differences in future meta-analyses.

Exosomal miRNA-146a-5p Derived from Senescent Hepatocellular Carcinoma Cells Promotes Aging and Inhibits Aerobic Glycolysis in Liver Cells via Targeting IRF7.

Hepatocellular carcinoma (HCC) is a major global health challenge. Chemotherapy can cause HCC cells to become senescent. Senescent HCC cells play an important role in inhibiting or promoting cancer by producing extracellular vesicles with a senescence-associated secretory phenotype (EV-SASP). miRNA can be strongly upregulated in EV-SASP during the aging process and can substantially alter the phenotypic characteristics of cells. MiRNA microarray analysis revealed that miRNA-146a-5p was highly expressed in oxaliplatin- and H2O2-induced senescent Huh7 cells, and RT‒PCR confirmed its significant upregulation in exosomes. The transcriptome sequencing results of Huh7 cells overexpressing miRNA-146a-5p suggested that miRNA-146a-5p could regulate HCC cell glycolysis. Subsequently, a dual luciferase assay was used to verify whether miRNA-146a-5p can interact with IRF7 to promote aging. The key functions of miRNA-146a-5p and IRF7 in aerobic glycolysis in liver cancer cells were determined through experiments analyzing glucose uptake, lactate production, the oxygen consumption rate (OCR) and the proton efflux rate (PER). Subsequently, the regulatory effect of IRF7 on the key glycolytic gene PFKL was confirmed through luciferase reporter assays. The western blot experiment results showed that miR-146a-5p can activate CHK2 and p53 phosphorylated proteins by targeting IRF7, and upregulate p21 protein. Overexpression of miRNA-146a-5p effectively inhibited the aerobic glycolytic function of HCC cells. Moreover, silencing IRF7 effectively inhibited aerobic glycolysis. MiR-146a-5p. MiR-146a-5p can activate the phosphorylation of CHK2 phosphorylation protein and its downstream protein p53 by targeting IRF7, and the activated p53 upregulates the expression of p21. Our study revealed that exosomal miRNA-146a-5p produced by aging HCC cells, can inhibit HCC cell proliferation through inhibiting aerobic glycolysis and promote HCC cell aging by activating CHK2/p53/p21 signaling way by targeting IRF7.

Lactobacillus rhamnosus NKU FL1-8 Isolated from Infant Feces Ameliorates the Alcoholic Liver Damage by Regulating the Gut Microbiota and Intestinal Barrier in C57BL/6J Mice.

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.

Transcriptome Analysis Reveals Cross-Talk between the Flagellar Transcriptional Hierarchy and Secretion System in Plesiomonas shigelloides.

Plesiomonas shigelloides, a Gram-negative bacillus, is the only member of the Enterobacteriaceae family able to produce polar and lateral flagella and cause gastrointestinal and extraintestinal illnesses in humans. The flagellar transcriptional hierarchy of P. shigelloides is currently unknown. In this study, we identified FlaK, FlaM, FliA, and FliAL as the four regulators responsible for polar and lateral flagellar regulation in P. shigelloides. To determine the flagellar transcription hierarchy of P. shigelloides, the transcriptomes of the WT and ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were carried out for comparison in this study. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and luminescence screening assays were used to validate the RNA-seq results, and the Electrophoretic Mobility Shift Assay (EMSA) results revealed that FlaK can directly bind to the promoters of fliK, fliE, flhA, and cheY, while the FlaM protein can bind directly to the promoters of flgO, flgT, and flgA. Meanwhile, we also observed type VI secretion system (T6SS) and type II secretion system 2 (T2SS-2) genes downregulated in the transcriptome profiles, and the killing assay revealed lower killing abilities for ΔflaK, ΔflaM, ΔfliA, and ΔfliAL compared to the WT, indicating that there was a cross-talk between the flagellar hierarchy system and bacterial secretion system. Invasion assays also showed that ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were less effective in infecting Caco-2 cells than the WT. Additionally, we also found that the loss of flagellar regulators causes the differential expression of some of the physiological metabolic genes of P. shigelloides. Overall, this study aims to reveal the transcriptional hierarchy that controls flagellar gene expression in P. shigelloides, as well as the cross-talk between motility, virulence, and physiological and metabolic activity, laying the groundwork for future research into P. shigelloides' coordinated survival in the natural environment and the mechanisms that infect the host.

Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study.

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between mitochondrial biological function and periodontitis, because the specific nature of this causal relationship remains inconclusive in existing MR studies. Inverse variance weighting, Mendelian randomization-Egger, weighted mode, simple mode, and weighted median analyses were performed to assess the causal relationships between the exposure factors and periodontitis. The results of the present study revealed a causal association between periodontitis and medium-chain specific acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), and pyruvate carboxylase (PC). Notably, MCAD and MLYCD are causally linked to periodontitis, and serve as protective factors. However, Grx2, ORN, and PC function as risk factors for periodontitis. Our study established a causal relationship between mitochondrial biological function and periodontitis, and such insights may provide a promising approach for treating periodontitis via mitochondrial regulation.

Open-angle glaucoma and Fuchs dystrophy.

A 62-year-old woman with a history of moderate myopia, long-standing open-angle glaucoma (OAG), and Fuchs dystrophy in both eyes was referred for consultative care. She had prior trabeculectomy in 1984 and 1992 in the left and right eyes, respectively. She is 3 months post-Descemet-stripping endothelial keratoplasty (DSEK) in the left eye, now referred with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy. Current medical therapy for IOP consists of acetazolamide 250 mg by mouth 2 times a day, brimonidine 2 times a day in the left eye, dorzolamide 2 times a day in the left eye, and timolol 2 times a day in the left eye. The patient has a history of presumed steroid response; however, her corneal surgeon has requested that the steroid be continued for the next several months because of the recent DSEK. The IOP in the left eye has ranged from the mid-20s to mid-30s since DSEK. The right eye has consistently had pressure in the low teens and below for many years without topical antihypertensive medications. Examination revealed stable visual acuity at 20/30 and 20/40 in the right and left eyes, respectively, IOP was 12 mm Hg in the right eye and 25 mm Hg in the left eye by Goldman applanation, irregular but reactive pupils without afferent defect, and full confrontational visual fields. Slitlamp examination showed superior low avascular bleb, moderate-to-severe guttae, and posterior chamber IOL in the right eye. The left eye showed superior low diffuse bleb, clear DSEK graft, quiet chamber, superonasal iridectomy, and posterior chamber IOL with an open posterior capsule. The conjunctiva was moderately scarred but a repeat trabeculectomy or Xen Gel stent (Abbvie) appeared possible. The angles were wide open in each eye. Fundus examination was normal aside from myopic, anomalous-appearing nerves with an approximate cup-to-disc ratio of 0.90 in both eyes. Humphrey visual field showed nonspecific changes on the right and moderate nasal defect on the left eye, stable to previous examinations dating back to 2018 (Figure 1JOURNAL/jcrs/04.03/02158034-202407000-00018/figure1/v/2024-07-10T174240Z/r/image-tiff and Figure 2JOURNAL/jcrs/04.03/02158034-202407000-00018/figure2/v/2024-07-10T174240Z/r/image-tiff). Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed moderated thinning in both eyes that was also stable to prior examinations (Figure 3JOURNAL/jcrs/04.03/02158034-202407000-00018/figure3/v/2024-07-10T174240Z/r/image-tiff). Her axial length measured 25.23 and 26.34 mm in the right and left eyes, respectively. Central corneal thickness was 553 µm in the right eye and 563 µm in the left eye before her DSEK procedure. What would be your approach to management of this patient's left eye, addressing the following: Rationale for your procedure of choice? Would you over-rule the corneal surgeon and stop the steroid in an attempt to obviate the need for glaucoma surgery? Does the age of onset of glaucoma affect your surgical decision making? Note that patient age at the time of trabeculectomy was 22 years. Are some procedures better suited for patients after DSEK surgery?

[ZHANG Weihua's experience in treatment of cervical spondylotic radiculopathy with ulna-tibia needling therapy combined with decompression-loosening manual manipulation].

The paper introduces professor ZHANG Weihua's experience in treatment of cervical spondylotic radiculopathy (CSR) with ulna-tibia needling therapy combined with decompression-loosening manual manipulation. Using "palpating, detecting and imaging observing", professor ZHANG Weihua gives the accurate diagnosis for the location, the stage and the severity of the disease. According to the nature of the disease, CSR is treated in three stages. He proposes the academic thought, "taking the tendons as the outline, regarding the meridians as the essential, rooting at qi and blood, co-regulating tendons and bones". The ulna-tibia needling therapy and decompression-loosening manual manipulation are combined in treatment. In the ulna-tibia needling therapy, the acupuncture is delivered at the lower 1/3 of the cutaneous regions of taiyang and shaoyang meridians, on the ulnar region (belt-like distribution). The decompression-loosening manual manipulation is operated in 3 steps, i.e. relaxing the nape region, decompressing and relaxing (includes positioning rotational wrenching, upward and backward elevation) and supination wrenching, and analgesia and regulating tendons; and the manipulation for analgesia and regulating tendons is supplemented to enhance the effect.

Isolation of Mitochondria from Murine Skeletal Muscle.

Skeletal muscle is one of the largest tissues in human body. Besides enabling voluntary movements and maintaining body's metabolic homeostasis, skeletal muscle is also a target of many pathological conditions. Mitochondria occupy 10-15% volume of a muscle myofiber and regulate many cellular processes, which often determine the fate of the cell. Isolation of mitochondria from skeletal muscle provides opportunities for various multi-omics studies with a focus on mitochondria in biomedical research field. Here we describe a protocol to efficiently isolate mitochondria with high quality and purity from skeletal muscle of mice using Nycodenz density gradient ultracentrifugation.