Scalable Customization of Crystallographic Plane Controllable Lithium Metal Anodes for Ultralong-Lasting Lithium Metal Batteries.

A formidable challenge to achieve the practical applications of rechargeable lithium (Li) metal batteries (RLMBs) is to suppress the uncontrollable growth of Li dendrites. One of the most effective solutions is to fabricate Li metal anodes with specific crystal plane, but still lack of a simple and high-efficient approach. Herein, a facile and controllable way for the scalable customization of polished Li metal anodes with highly preferred (110) and (200) crystallographic orientation (donating as polished Li(110) and polished Li(200), respectively) by regulating the times of accumulative roll bonding, is reported. According to the inherent characteristics of polished Li(110)/Li(200), the influence of Li atomic structure on the electrochemical performance of RLMBs is deeply elucidated by combining theoretical calculations with relative experimental proofs. In particular, a polished Li(110) crystal plane is demonstrated to induce Li+ uniform deposition, promoting the formation of flat and dense Li deposits. Impressively, the polished Li(110)||LiFePO4 full cells exhibit unprecedented cycling stability with 10 000 cycles at 10 C almost without capacity degradation, indicating the great potential application prospect of such textured Li metal. More valuably, this work provides an important reference for low-cost, continued, and large-scale production of Li metal anodes with highly preferred crystal orientation through roll-to-roll manufacturability.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Adverse Events in Total Artificial Heart for End-Stage Heart Failure: Insight From the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE).

Background and Objectives: Real-world clinical data, outside of clinical trials and expert centers, on adverse events related to the use of SyncCardia total artificial heart (TAH) remain limited. We aim to analyze adverse events related to the use of SynCardia TAH reported to the Food and Drug Administration (FDA)'s Manufacturers and User Defined Experience (MAUDE) database. Methods: We reviewed the FDA's MAUDE database for any adverse events involving the use of SynCardia TAH from 1/01/2012 to 9/30/2020. All the events were independently reviewed by three physicians. Results: A total of 1,512 adverse events were identified in 453 "injury and death" reports in the MAUDE database. The most common adverse events reported were infection (20.2%) and device malfunction (20.1%). These were followed by bleeding events (16.5%), respiratory failure (10.1%), cerebrovascular accident (CVA)/other neurological dysfunction (8.7%), renal dysfunction (7.5%), hepatic dysfunction (2.2%), thromboembolic events (1.8%), pericardial effusion (1.8%), and hemolysis (1%). Death was reported in 49.4% of all the reported cases (n=224/453). The most common cause of death was multiorgan failure (n=73, 32.6%), followed by CVA/other non-specific neurological dysfunction (n=44, 19.7%), sepsis (n=24, 10.7%), withdrawal of support (n=20, 8.9%), device malfunction (n=11, 4.9%), bleeding (n=7, 3.1%), respiratory failure (n=7, 3.1%), gastrointestinal disorder (n=6, 2.7%), and cardiomyopathy (n=3, 1.3%). Conclusions: Infection was the most common adverse event following the implantation of TAH. Most of the deaths reported were due to multiorgan failure. Early recognition and management of any possible adverse events after the TAH implantation are essential to improve the procedural outcome and patient survival.

Reproductive Ability Disparity in the Pacific Whiteleg Shrimp (Penaeus vannamei): Insights from Ovarian Cellular and Molecular Levels.

The Pacific whiteleg shrimp (Penaeus vannamei) is a highly significant species in shrimp aquaculture. In the production of shrimp larvae, noticeable variations in the reproductive capacity among female individuals have been observed. Some females experience slow gonadal development, resulting in the inability to spawn, while others undergo multiple maturations and contribute to the majority of larval supply. Despite numerous studies that have been conducted on the regulatory mechanisms of ovarian development in shrimp, the factors contributing to the differences in reproductive capacity among females remain unclear. To elucidate the underlying mechanisms, this study examined the differences in the ovarian characteristics between high and low reproductive bulks at different maturity stages, focusing on the cellular and molecular levels. Transmission electron microscopy analysis revealed that the abundance of the endoplasmic reticulum, ribosomes, mitochondria, and mitochondrial cristae in oocytes of high reproductive bulk was significantly higher than that of the low reproductive bulk in the early stages of ovarian maturation (stages I and II). As the ovaries progressed to late-stage maturation (stages III and IV), differences in the internal structures of oocytes between females with different reproductive capacities gradually diminished. Transcriptome analysis identified differentially expressed genes (DEGs) related to the mitochondria between two groups, suggesting that energy production processes might play a crucial role in the observed variations in ovary development. The expression levels of the ETS homology factor (EHF) and PRDI-BF1 and RIZ homology domain containing 9 (PRDM9), which were significantly different between the two groups, were compared using qRT-PCR in individuals at different stages of ovarian maturation. The results showed a significantly higher expression of the EHF gene in the ovaries of high reproductive bulk at the II and IV maturity stages compared to the low reproductive bulk, while almost no expression was detected in the eyestalk tissue of the high reproductive bulk. The PRDM9 gene was exclusively expressed in ovarian tissue, with significantly higher expression in the ovaries of the high reproductive bulk at the four maturity stages compared to the low reproductive bulk. Fluorescence in situ hybridization further compared the expression patterns of EHF and PRDM9 in the ovaries of individuals with different fertility levels, with both genes showing stronger positive signals in the high reproductive bulk at the four ovarian stages. These findings not only contribute to our understanding of the regulatory mechanisms involved in shrimp ovarian development, but also provide valuable insights for the cultivation of new varieties aimed at improving shrimp fecundity.

Analysis of cancer-associated fibroblasts related genes identifies COL11A1 associated with lung adenocarcinoma prognosis.

BACKGROUND: The treatment of lung adenocarcinoma is difficult due to the limited therapeutic options. Cancer-associated fibroblasts play an important role in the development of cancers. This study aimed to identify a promising molecular target associated with cancer-associated fibroblasts for the treatment of lung adenocarcinoma. METHODS: The Cancer Genome Atlas lung adenocarcinoma dataset was used to screen hub genes associated with cancer-associated fibroblasts via the EPIC algorithm and Weighted Gene Co-expression Network Analysis. Multiple databases were used together with our data to verify the differential expression and survival of COL11A1. Functional enrichment analysis and the single-cell TISCH database were used to elucidate the mechanisms underlying COL11A1 expression. The correlation between COL11A1 and immune checkpoint genes in human cancers was also evaluated. RESULTS: Using the EPIC algorithm and Weighted Gene Co-expression Network Analysis, 13 hub genes associated with cancer-associated fibroblasts in lung adenocarcinoma were screened. Using the GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, GSE32863, and our immunohistochemistry experiment data, we confirmed that COL11A1 overexpresses in lung adenocarcinoma and that high expression of COL11A1 is associated with a poor prognosis. COL11A1 has a genetic alteration frequency of 22% in patients with lung adenocarcinoma. COL11A1 is involved in the extracellular matrix activities of lung adenocarcinoma. Using the TISCH database, we found that COL11A1 is mainly expressed by cancer-associated fibroblasts in the tumor microenvironment rather than by lung adenocarcinoma cells. Finally, we found that COL11A1 is positively correlated with HAVCR2(TIM3), CD274 (PD-L1), CTLA4, and LAG3 in lung adenocarcinoma. CONCLUSION: COL11A1 may be expressed and secreted by cancer-associated fibroblasts, and a high expression of COL11A1 may result in T cell exhaustion in the tumor microenvironment of lung adenocarcinoma. COL11A1 may serve as an attractive biomarker to provide new insights into cancer therapeutics.

[Effect of different cleaning methods on bond strength and surface wettability of high translucency zirconia].

PURPOSE: To study the effect of different cleaning methods on the shear bond strength of self-adhesive resin cement to saliva-contaminated high translucency zirconia and surface wettability. METHODS: Eighty zirconia specimens were randomly divided into 5 groups (n=16), i.e., control group(not contaminated), 75% ethanol group,cleaning paste group,airborne-particle abrasion group, and atmospheric pressure cold plasma group. The contact angles was measured, shear bond strength were examined, and fracture types were determined. SPSS 26.0 software package was used for statistical analysis of the data. RESULTS: The atmospheric pressure cold plasma group produced the lowest contact angle(P＜0.05). The shear bond strength of the airborne-particle abrasion group, the cleaning paste group and the atmospheric pressure cold plasma group respectively were similar to the control group without significant difference(P＞0.05), while those were significantly higher than 75% ethanol group(P＜0.05). The mixed fracture mode of the atmospheric pressure cold plasma group evidently increased. CONCLUSIONS: Airborne-particle abrasion, cleaning paste and atmospheric pressure cold plasma overcome the effects of saliva contamination, producing the shear bond strength to zirconia similar to the control group. The atmospheric pressure cold plasma improves hydrophilicity of high translucency zirconia significantly.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Comprehensive analysis of lung adenocarcinoma: Unveiling differential gene expression, survival-linked genes, subtype stratification, and immune landscape implications.

This study offers a detailed exploration of lung adenocarcinoma (LUAD), addressing its heterogeneity and treatment challenges through a multi-faceted analysis that includes gene expression, genetic subtyping, pathway analysis, immune assessment, and drug sensitivity. It identifies 165 genes with significant expression differences and 46 genes associated with survival, revealing insights into oxidative stress and autophagy. LUAD samples were divided into three subtypes using consensus clustering on these 46 genes, with distinct survival outcomes. Gene Set Enrichment Analysis (GSEA) on HALLMARK gene sets indicated pathway variations with survival implications. The immune landscape, analyzed using the CIBERSORT algorithm, showed different immune cell distributions across subtypes, with the first subtype exhibiting a better immune environment and survival prospects. Advanced machine learning techniques developed a risk model from a set of four genes, effectively categorizing patients into high and low-risk groups, validated through external datasets and analyses. This model linked lower risk scores to better clinical stages, with a higher mutation rate and potential immunotherapy benefits observed in the high-risk group. Drug sensitivity assessments highlighted varied treatment responses between risk groups, suggesting avenues for personalized therapy. This comprehensive analysis enhances the understanding of LUAD's molecular and clinical nuances, offering valuable insights for tailored treatment approaches.

Myeloperoxidase Gene Deletion Causes Drastic Microbiome Shifts in Mice and Does Not Mitigate Dextran Sodium Sulphate-Induced Colitis.

Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models.

Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina.

BACKGROUND: Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, leading to visual impairment. Retinal pigment epithelium (RPE) injury is a key component of the outer blood retinal barrier, and its damage is an important indicator of DR. Receptor for activated C kinase 1 (RACK1) activates protein kinase C-ε (PKC-ε) to promote the generation of reactive oxygen species (ROS) in RPE cells, leading to apoptosis. Therefore, we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS, thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR. AIM: To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR. METHODS: In this study, Sprague-Dawley rats and adult RPE cell line-19 (ARPE-19) cells were used as in vivo and in vitro models, respectively, to explore the role of RACK1 in mediating PKC-ε in early DR. Furthermore, the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model. RESULTS: Streptozotocin-induced diabetic rats showed increased apoptosis and up-regulated expression of RACK1 and PKC-ε proteins in RPE cells following a prolonged modeling. Similarly, ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε, accompanied by an increases in ROS production, apoptosis rate, and monolayer permeability. However, silencing RACK1 significantly downregulated the expression of PKC-ε and ROS, reduced cell apoptosis and permeability, and protected barrier function. CONCLUSION: RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.

Impact of Sarcoidosis on In-hospital Outcomes Among Patients with Atrial Fibrillation: A Nationwide Readmissions Database Analysis.

Sarcoidosis is a disease that involves multiple organs, including the cardiovascular system. While cardiac sarcoidosis has been increasingly recognized, the impact of sarcoidosis on atrial fibrillation (AF) is not well established. This study aimed to analyze the impact of sarcoidosis on in-hospital outcomes among patients who were admitted for a primary diagnosis of AF. Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged ≥18 years who were admitted for AF between 2017-2020. We stratified the cohort into two groups depending on the presence of sarcoidosis diagnosis. The in-hospital outcomes were assessed between the two groups via propensity score analysis. A total of 1031 (0.27%) AF patients with sarcoidosis and 387,380 (99.73%) AF patients without sarcoidosis were identified in our analysis. Our propensity score analysis of 1031 (50%) patients with AF and sarcoidosis and 1031 (50%) patients with AF but without sarcoidosis revealed comparable outcomes in early mortality (1.55% vs. 1.55%, P = 1.000), prolonged hospital stay (9.51% vs. 9.70%, P = .874), non-home discharge (7.95% vs. 9.89%, P = .108), and 30-day readmission (13.29% vs. 13.69%, P = .797) between the two groups. The cumulative cost of hospitalization was also similar in both groups ($12,632.25 vs. $12,532.63, P = .839). The in-hospital adverse event rates were comparable in both groups. Sarcoidosis is not a risk factor for poorer in-hospital outcomes following AF admission. These findings provide valuable insights into the effectiveness of the current guideline for AF management in patients with concomitant sarcoidosis and AF.

Prognostic factors for postoperative papillary thyroid cancer with unexplained elevated Tg: A retrospective study.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. Results: A cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. Conclusion: The proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

Prenatal inflammation exposure accelerates lung cancer tumorigenesis in offspring mouse: possible links to IRE1α/XBP1-mediated M2-like polarization of TAMs and PD-L1 up-expression.

BACKGROUND: Prenatal inflammation exposure (PIE) can increase the disease susceptibility in offspring such as lung cancer. Our purpose was to investigate the mechanisms of PIE on lung cancer. METHODS: Prenatal BALB/c mice were exposed to lipopolysaccharide (LPS), and then, their offspring were intraperitoneally instilled with urethane to establish the two-stage lung cancer carcinogenesis model. At the 48 weeks of age, the offspring mice were killed and lung tissues were collected for HE, immunohistochemistry, immunofluorescence, and Luminex MAGPIX®-based assays. CD11b + F4/80 + tumor-associated macrophages (TAMs) were sorted out from lung tumor tissues by cell sorting technique. Flow cytometry was employed to evaluate the extent of M2-like polarization of TAMs and PD-L1 expression. RESULTS: The offspring of PIE mice revealed more lung lesion changes, including atypical hyperplasia and intrapulmonary metastases. The number of lung nodules, lung organ index, and PCNA, MMP-9 and Vimentin positive cells in lung tissue of PIE group were higher than those of Control group. The increases of mRNA encoding M2 macrophage markers and cytokines in offspring of prenatal LPS-treated mice confirmed the induced effect of PIE on macrophage polarization. Additionally, PIE treatment increased the percentage of CD163 + CD206 + cells in the sorted TAMs. Importantly, endoplasmic reticulum (ER) stress-markers like GRP78/BIP and CHOP, p-IRE1α and XBP1s, and PD-L1 were up-regulated in TAMs from PIE group. Besides, we also observed that IRE1α inhibitor (KIRA6) reversed the M2-like TAMs polarization and metastasis induced by PIE. CONCLUSIONS: IRE1α/XBP1-mediated M2-like TAMs polarization releases the pro-tumorigenic cytokines and PD-L1 expression, which may be the regulatory mechanism of accelerating lung cancer in offspring of mice undergoing PIE.

Trends and Disparities in Cardiovascular Death in Sarcoidosis: A Population-Based Retrospective Study in the United States From 1999 to 2020.

BACKGROUND: Despite significant cardiac involvement in sarcoidosis, real-world data on death due to cardiovascular disease among patients with sarcoidosis is not well established. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database for data on patients with sarcoidosis aged ≥25 years from 1999 to 2020. Diseases of the circulatory system except ischemic heart disease were listed as the underlying cause of death, and sarcoidosis was stated as a contributing cause of death. We calculated age-adjusted mortality rate (AAMR) per 1 million individuals and determined the trends over time by estimating the annual percentage change using the Joinpoint Regression Program. Subgroup analyses were performed on the basis of demographic and geographic factors. In the 22-year study period, 3301 cardiovascular deaths with comorbid sarcoidosis were identified. The AAMR from cardiovascular deaths with comorbid sarcoidosis increased from 0.53 (95% CI, 0.43-0.65) per 1 million individuals in 1999 to 0.87 (95% CI, 0.75-0.98) per 1 million individuals in 2020. Overall, women recorded a higher AAMR compared with men (0.77 [95% CI, 0.74-0.81] versus 0.58 [95% CI, 0.55-0.62]). People with Black ancestry had higher AAMR than people with White ancestry (3.23 [95% CI, 3.07-3.39] versus 0.39 [95% CI, 0.37-0.41]). A higher percentage of death was seen in the age groups of 55 to 64 years in men (23.11%) and women (21.81%), respectively. In terms of US census regions, the South region has the highest AAMR from cardiovascular deaths with comorbid sarcoidosis compared with other regions (0.78 [95% CI, 0.74-0.82]). CONCLUSIONS: The increase of AAMR from cardiovascular deaths with comorbid sarcoidosis and higher cardiovascular mortality rates among adults aged 55 to 64 years highlight the importance of early screening for cardiovascular diseases among patients with sarcoidosis.

Transorbital and endonasal resection of a rare orbital ectopic atypical meningioma.

A female patient in her early 20s presented with increasing proptosis of her left eye over 2 months. She had no other signs of diplopia, pain or visual loss on initial presentation. Subsequent imaging of her orbits revealed a medial rectus tumour. A transorbital open biopsy of this tumour was non-diagnostic/inconclusive, hence a combined transorbital and endonasal resection of this tumour was performed. Histopathology of the resected tumour revealed an unusual inflammatory-rich spindle cell neoplasm, which was determined to be a primary orbital ectopic atypical meningioma. These tumours are exceedingly rare, with only case reports/series reported in the literature. Complete surgical resection with margins is the proposed treatment. The role of radiotherapy is still controversial. More studies are required to improve our knowledge of this condition.

Breastfeeding is associated with enhanced intestinal gluconeogenesis in infants.

BACKGROUND: Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants. METHODS: Previous literatures directly studying the influences of BF on offspring's metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed. RESULTS: Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis. CONCLUSIONS: BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance.

Fermentable sugar recovery from durian peel by using ultrasound-assisted chemical pretreatment.

Durian peel, an abundant waste in Malaysia could be a potential substrate for fermentable sugar recovery for value-added biochemical production. Common pretreatment such as acid or alkaline pretreatment resulted in the need for extensive solid washing which generated wastewater. Herein, this study aims to introduce sonication on top of chemical pretreatment to destruct lignin and reduce the chemical usage during the durian peel pretreatment process. In this study, the morphology and the chemical composition of the pretreated durian peels were studied. The sugar yield produced from the chemical pretreatment and the combined ultrasound and chemical pretreatment were compared. The morphology and chemical structure of durian peels were investigated by Scanning Electron Microscope (SEM), Fourier Transform Infrared (FTIR) analysis and X-ray diffraction (XRD). The SEM images showed that the structural change became more significant when sonication was introduced. Second, XRD profile indicated a relatively higher crystallinity index and FTIR spectra displayed a lower intensity of lignin and hemicellulose for ultrasound plus alkaline (UB) pretreatment as compared to acid, alkaline and ultrasound plus acid (UA) pretreatment. UB and UA pretreatment portrayed higher yield (376.60 ± 12.14 and 237.38 ± 3.96 mg reducing sugar/g dry biomass, respectively) than their controls without the application of ultrasound. Therefore, it could be concluded that ultrasound was able to intensify the fermentable sugar recovery from durian peel by inducing physical and chemical effect of cavitation to alter the morphology of durian peel. Fermentation of UB treated durian peel resulted in 2.68 mol hydrogen/mol consumed sugar and 131.56 mL/Lmedium/h of hydrogen productivity. This study is important because it will shed light on a way to handle durian waste disposal problems and generate fermentable sugars for the production of high value-added products.