Delayed Lithium Reintoxication in a Case of Severe Multidrug Intoxication: A Case Study.

ABSTRACT: The authors present a case of severe multidrug intoxication following massive ingestion of lithium, nortriptyline, aripiprazole, lorazepam, and temazepam. After initial treatment, serum lithium levels decreased significantly. However, 28 hours post ingestion, recurrent elevated lithium levels were observed, and serum lithium level increased 0.71 mmol/L in 12 hours. The intensivist consulted a hospital pharmacist about this. After administering clearance-inducing therapy using continuous venovenous hemodialysis, the lithium level was reduced to a long-lasting nontoxic level. The occurrence of secondary elevation in lithium levels exceeding the toxic limit in cases of massive ingestion of lithium tablets, whether in combination with anticholinergic drugs, should be anticipated. Close monitoring and prompt initiation of clearance-inducing therapy can improve clinical outcomes.

Management of cognitive frailty: A network meta-analysis of randomized controlled trials.

OBJECTIVES: We aimed to compare the effectiveness of interventions in cognitive function and frailty status and rank these interventions. METHODS: Data Sources-We searched PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, VIP and Google scholar. Data synthesis-The risk of bias was assessed using the Cochrane risk bias assessment tool. Statistical heterogeneity was assessed using the Chi-square test and quantified by I2 . The results were pooled using the standardized mean difference (SMD). The rank probability for each intervention was calculated using the surface under the cumulative ranking curve (SUCRA). Additionally, the quality of the evidence was evaluated using the GRADE approach. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 1110 patients were included in our analysis. The network map of cognitive function comprised 9 RCTs with 1347 participants, examining eight different interventions. Nutritional support (SUCRA = 99.9%, SMD = 3.02, 95% CI: 2.53, 3.51) may be the most effective intervention to improve cognitive function. The network map of frailty (including 9 RCTs with 1017 participants and 9 interventions) suggested that multicomponent exercises (SUCRA = 96.4%, SMD = -5.10, 95% CI: -5.96, -4.23) tended to have a greater effect. CONCLUSIONS: Community-based multicomponent exercises have shown significant benefits for improving cognitive function and frailty status in older adults, with moderate certainty. For hospitalized older patients with Cognitive frailty (CF), current evidence suggests that nutritional support yields the most improvement. Additionally, aerobic exercise and dual-task training have proven effective in managing CF. Further studies are needed to validate these preliminary findings and exploring more accessible and effective physical and cognitive interventions to prevent CF in aging.

Effects of Ruxolitinib on Myeloproliferative Neoplasms via the Negative Regulators.

BACKGROUND: We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleukemia (HEL) cells, which had JAK2V617F mutation. METHODS: Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by immunohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits. RESULTS: 1. The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 expressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a significant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and -7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p ＜ 0.01, p ＜ 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p ＜ 0.01).

Risk analysis of the Unity 1.5 T MR-Linac adapt-to-position workflow.

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps. METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed. RESULTS: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations. CONCLUSION: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust.

Global perspectives for biochar application in the remediation of heavy metal-contaminated soil: a bibliometric analysis over the past three decades.

Herein, 7,308 relevant documents on biochar application for the remediation of heavy metal (HM)-contaminated soil (BARHMCS) from 1991 to 2020 were extracted from the Web of Science Core Collection and subjected to bibliometric and knowledge mapping analyses to provide a global perspective. The results showed that (1) the number of publications increased over time and could be divided into two subperiods, i.e., the slow growth period (SGP) and rapid growth period (RGP), according to whether the annual publication number was ≥300. (2) A total of 126 countries, 741 institutions, and 1,021 scholars have contributed to this field. (3) These studies are mainly published in Science of the Total Environment, Chemosphere, etc., and are mainly based on the categories of environmental science, soil science, and environmental engineering. (4) The top five keyword clusters for the SGP were biochar, biochar, sorption, charcoal, and HMs, and those for the RGP were adsorption, black carbon, nitrous oxide, cadmium, and pyrolysis. (5) The main knowledge domains and the most cited references during the SGP and RGP were discussed. (6) Future directions are related to biochar application for plant remediation, the mitigation of climate change through increased carbon sequestration, biochar modification, and biochar for HMs and multiple organic pollutants.

Biochar application in the remediation of heavy metal-contaminated soil (BARHMCS) has become a popular research topic worldwide. Many excellent papers on this topic have been published, including some valuable reviews. However, there are no reviews including bibliometric and visual analyses. In the present study, bibliometric and visual analyses of relevant literature in the field of BARHMCS based on the Web of Science Core Collection were carried out to outline the development process of this field at a macro level, clarify the research hotspots, identify the knowledge domains that support this field, and explore future research directions. These efforts will no doubt help readers fully understand BARHMCS from a global perspective and provide a reference for future research. HIGHLIGHTSAn overall global perspective of biochar remediation of heavy metal (HM)-contaminated soil was provided.The main popular research topics of each period were discussed.Knowledge domains were discussed.Five main future research directions were identified based on burst keyword analysis.Biochar modification and its effect on HMs and coexisting organic pollutants should be studied in the future for soil remediation purposes.

Involvement of intestinal flora and miRNA into the mechanism of coarse grains improving type 2 diabetes: an overview.

The prevalence of type 2 diabetes has been growing at an increasing rate worldwide. Dietary therapy is probably the easiest and least expensive method to prevent and treat diabetes. Previous studies have reported that coarse grains have anti-diabetic effects. Although considerable efforts have been made on the anti-diabetic function of different grains, the mechanisms of coarse grains on type 2 diabetes have not been systematically compared and summarized so far. Intestinal flora, reported as the main 'organ' of action underlying coarse grains, is an important factor in the alleviation of type 2 diabetes by coarse grains. Furthermore, microRNA (miRNA), as a new disease marker and 'dark nutrient', plays a likely influential role in cross-border communication among coarse grains, intestinal flora, and hosts. Given this context, this article reviews several possible mechanisms for the role of coarse grains on diabetes, incorporating resistance to inflammation and oxidative stress, repair of insulin signaling and ß-cell dysfunction, and highlights the regulation of intestinal flora disorders and miRNAs expression, along with some novel insights. © 2022 Society of Chemical Industry.

A Metallofullertube of Ce2 @C100 with a Carbon Nanotube Segment: Synthesis, Single-Molecule Conductance and Supramolecular Assembly.

Tubular fullerenes can be considered as end-capped carbon nanotubes with accurate structure, which are promising nanocarbon materials for advanced single-molecule electronic devices. Herein, we report the synthesis and characterization of a metallofullertube Ce2 @D5 (450)-C100 , which has a tubular C100 cage with a carbon nanotube segment and two fullerene end-caps. As there are structure correlations between tubular Ce2 @D5 (450)-C100 and spherical Ce2 @Ih -C80 , their structure-property relationship has been compared by means of experimental and theoretical methods. Notably, single-molecule conductance measurement determined that the conductivity of Ce2 @D5 (450)-C100 was up to eight times larger than that of Ce2 @Ih -C80 . Furthermore, supramolecular assembly of Ce2 @D5 (450)-C100 and a [12]CPP nanohoop was investigated, and theoretical calculations revealed that metallofullertube Ce2 @D5 (450)-C100 adopted a "standing" configuration in the cavity of [12]CPP. These results demonstrate the special nature of this kind of metallofullertube.

Genome-wide identification, and phylogenetic and expression profiling analyses, of XTH gene families in Brassica rapa L. and Brassica oleracea L.

BACKGROUND: Xyloglucan endotransglucosylase/hydrolase genes (XTHs) are a multigene family and play key roles in regulating cell wall extensibility in plant growth and development. Brassica rapa and Brassica oleracea contain XTHs, but detailed identification and characterization of the XTH family in these species, and analysis of their tissue expression profiles, have not previously been carried out. RESULTS: In this study, 53 and 38 XTH genes were identified in B. rapa and B. oleracea respectively, which contained some novel members not observed in previous studies. All XTHs of B. rapa, B. oleracea and Arabidopsis thaliana could be classified into three groups, Group I/II, III and the Early diverging group, based on phylogenetic relationships. Gene structures and motif patterns were similar within each group. All XTHs in this study contained two characteristic conserved domains (Glyco_hydro and XET_C). XTHs are located mainly in the cell wall but some are also located in the cytoplasm. Analyses of the mechanisms of gene family expansion revealed that whole-genome triplication (WGT) events and tandem duplication (TD) may have been the major mechanisms accounting for the expansion of the XTH gene family. Interestingly, TD genes all belonged to Group I/II, suggesting that TD was the main reason for the largest number of genes being in these groups. B. oleracea had lost more of the XTH genes, the conserved domain XET_C and the conserved active-site motif EXDXE compared with B. rapa, consistent with asymmetrical evolution between the two Brassica genomes. A majority of XTH genes exhibited different tissue-specific expression patterns based on RNA-seq data analyses. Moreover, there was differential expression of duplicated XTH genes in the two species, indicating that their functional differentiation occurred after B. rapa and B. oleracea diverged from a common ancestor. CONCLUSIONS: We carried out the first systematic analysis of XTH gene families in B. rapa and B. oleracea. The results of this investigation can be used for reference in further studies on the functions of XTH genes and the evolution of this multigene family.

Impact of varying air cavity on planning dosimetry for rectum patients treated on a 1.5 T hybrid MR-linac system.

PURPOSE: To investigate the dosimetric impact of magnetic (B) field on varying air cavities in rectum patients treated on the hybrid 1.5 T MR-linac. METHODS: Artificial air cavities of varying diameters (0.0, 1.0, 1.5, 2.0, 2.5, 3.0, and 5.0 cm) were created for four rectum patients (two prone and two supine). A total of 56 plans using a 7 MV flattening filter-free beam were generated with and without B-field. Reference intensity-modulated radiation therapy treatment plans without air cavity in the presence and absence of B-field were generated to a total dose of 45/50 Gy. The reference plans were copied and recalculated for the varying air cavities. D95 (PTV45 -PTV50 ), D95 (PTV50 -aircavity), V50 (PTV50 -aircavity), Dmax (PTV50 -aircavity), and V110% (PTV50 -aircavity) were extracted for each patient. Annulus rings of 1-mm-diameter step size were generated for one of the air cavity plans (3.0 cm) for all four patients to determine Dmax (%) and V110% (cc) within each annulus. RESULTS: In the presence of B-field, hot spots at the cavity interface start to become visible at ~1 cm air cavity in both supine and prone positioning due to electron return effect (ERE). In the presence of B-field Dmax and V110% varied from 5523 ± 49 cGy and 0.09 ± 0.16 cc for 0 cm air cavity size to 6050 ± 109 cGy and 11.6 ± 6.7 cc for 5 cm air cavity size. The hot spots were located within 3 mm inside the rectal-air interface, where Dmax increased from 110.4 ± 0.5% without B-field to 119.2 ± 0.8 % with B-field. CONCLUSIONS: Air cavities inside rectum affects rectum plan dosimetry due ERE. Location and magnitude of hot spots are dependent on the size of the air cavity.

[Common Walking Fault of Multileaf Collimator in Linear Accelerator].

This paper introduces the failure phenomenon, failure analysis, maintenance process and method of SIEMENS PRIMUS linear accelerator.

Mitochondrial estrogen receptor ß inhibits cell apoptosis via interaction with Bad in a ligand-independent manner.

Previous studies reported that estrogen receptor ß (ERß) is localized to mitochondria, whereas little is known about the physiological functions of mitochondrial ERß. In the present study, we explored the role of mitochondrial ERß in regulating apoptosis using stable ERß-expressing and ERß knockdown cells lines. We found that exogenous ERß was mainly expressed in mitochondrial but not in nuclear after ERß overexpression and protected cells from apoptosis induced by hydrogen peroxide (H2O2), ultraviolet (UV), and staurosporine (STS). Moreover, overexpression of ERß prevented Bax activation, cytochrome c release, caspase-3 activation, and PARP cleavage during apoptosis. Furthermore, knockdown of ERß significantly suppressed the expression of ERß in mitochondrial and promoted cell apoptosis induced by H2O2, UV, and STS. Downregulation of ERß also enhanced Bax activation, cytochrome c release, caspase-3 activation and PARP cleavage. In addition, our study discovered that mitochondrial ERß interacted with proapoptotic protein Bad in a ligand-independent manner, which suggests that mitochondrial ERß inhibits Bad, and prevents Bax activation and cytochrome c release. Collectively, the results of this study support that mitochondrial ERß prevents cell apoptosis via the mitochondrial apoptotic pathway in a ligand-independent manner.

The imaging features of ectopic spleen: which modality is more consistent? A cases series report and literature reviews.

Ectopic spleen (ES) is a rare condition. It is difficult to diagnose with conventional imaging modalities. In this case series, we presented the imaging features of three misdiagnosed ES cases in our hospital and previously reported cases to compare the consistency of enhancement patterns among different imaging modalities with varied phases. Finally, 22 cases were reviewed. We determined that variable arterial phase enhancement and persistent enhancement throughout the portal and delayed phases are present in contrast-enhanced ultrasound (CEUS) imaging of the ES and found the arterial phase of CEUS had the highest consistency compared with computerized tomography (CT) and magnetic resonance imaging (MRI).

Clear-cell papillary renal cell tumour: New insights into clinicopathological features and molecular landscape after renaming by 5th WHO classification.

OBJECTIVE: Clear cell papillary renal cell tumour (CCPRCT) is a kind of renal epithelial cell tumor, and was renamed by the 5th WHO due to its specific epidemiology and clinicopathological characteristics. However, the biological mechanism and molecular basis of CCPRCT still need to be further clarified. This study aims to comprehensively evaluate clinicopathologic and molecular characteristics of CCPRCC, and particularly compare it with other more prevalent subtypes of renal cell carcinoma. METHODS: 12 cases of CCPRCT were collected for analyzing the clinicopathological characteristics. Then, whole-exome sequencing (WES) was employed to reveal the genetic profiles, followed by comparison with the molecular genetic alterations identified in ccRCC (341) and pRCC (200) datasets obtained from the TCGA database. RESULTS: Of the 12 CCPRCT cases, the male-to-female ratio was 4:1 with a mean age of 49.5 years (48.5 ± 10.5) at diagnosis. All patients were diagnosed accidentally during routine physical examinations. All tumors (12/12, 100%）had a solid-cystic appearance with a well-defined fibrous capsule. The median size of the tumors was 3 cm (2.98 ± 1.2). Histologically, the cystic papillary structures were considered to be prominent, lined with cuboidal tumor cells away from basement membrane. The tumor cells were moderately atypia equivalent to grade 1 or grade 2 according to the ISUP nuclear grading system. Typically, the tumor cell diffusely positive for CK7 and CAIX in a "cup-like" pattern. The results of WES revealed recurrent gene alterations (mainly missense mutation) of TTN and FLT in 4 cases (4/12, 33.3%), respectively, of which, the alteration of FLT was not observed in ccRCC and pRCC of the TCGA database. Other gene alterations including POTEC (1 cases), PRADC1 (1 cases), ZZZ3 (1 case) and PTPRZ1 (1 case), etc. Moreover, all of the CCPRCT cases displayed a lower tumor mutation burden (TMB) compared to ccRCC and pRCC with median TMB of 1.04 (range: 1.94 ± 2.74). None of the patients experienced tumor metastasis, recurrence, or tumor-related deaths. CONCLUSION: CCPRCT is a renal epithelial cell tumor characterized by specific clinical and pathological features. Our study provides additional evidence supporting the favorable prognosis of CCPRCT. Furthermore, the potential molecular alterations were uncovered by this study in CCPRCT such as the FLT family and TTN. However, due to the limited sample size, larger studies are required to validate these findings.

Metatranscriptomic profiles reveal the biotransformation potential of azithromycin in river periphyton.

Assessment of the interaction between the biotransformation of chemical contaminants and enzyme activity from aquatic microbial communities is critical for improving the micropollutant degradation in river remediation. Here, association mining based on metatranscriptomic analysis was initially applied to determine the genes encoding enzymes involved in the azithromycin (AZI) transformation process and the corresponding microbial hosts in periphyton, followed by revealing the dynamic variation in the community structure and function. In terms of the biotransformation potential, the highly correlated 15 enzymes were suggested to be primarily involved in AZI biotransformation, energy supply, and antibiotic resistance processes, especially aryl-alcohol dehydrogenases (EC: 1.1.1.90), hydroxylamine dehydrogenase (EC: 1.7.2.6), and monooxygenases (EC: 1.14.11.57) that were involved in the biotransformation of AZI. In the matter of community ecological function, the photosystem II (PSII) reaction center in the periphytic photosynthetic process, as indicated by Fv/Fm, was inhibited after AZI exposure, which may be attributed to the down-regulated genes enriched in the photosynthesis - antenna proteins (ko00196), photosynthesis (ko00195), and two-component system (ko02020) pathways. Furthermore, the periphytic utilization capacity for carbohydrates and phenolic acids was enhanced, which was in accordance with all the increased expression of transcripts involved in the corresponding molecular pathways, including aminobenzoate degradation (ko00627), starch and sucrose metabolism (ko00500), ABC transporters (ko02010), phosphotransferase system (ko02060), galactose metabolism (ko00052), amino sugar and nucleotide sugar metabolism (ko00520). Taken together, this study highlighted the critical role of river periphyton in the micropollutant degradation and unraveled the molecular mechanism of antibiotic biotransformation as well as the structural and functional damage in the periphyton.

Seasonal variation in structural and functional distribution of periphyton in a macrolide antibiotics-contaminated river.

Periphyton, a microbial assemblage of autotrophic and heterotrophic organisms, is vital to aquatic ecosystems. While exposure to macrolide antibiotics has been confirmed to reduce the biodiversity and damage the critical ecological functions in indoor microcosm bioassays, the distribution of periphyton along a macrolide antibiotic pollution gradient in a river has yet to be determined. Herein, we established the spatiotemporal distribution of five major macrolides, i.e., azithromycin (AZI), roxithromycin (ROX), erythromycin (ERY), clarithromycin (CLA), and anhydro erythromycin (ERY-H2O) in water and periphyton of Zao River (Xi'an, China), after which we evaluated the effects on the structures, photosynthetic activity, and carbon utilization capacity of periphyton in March, June, and September 2023. In contrast with the reference sites, the macrolides were identified in all sewage treatment plants (STPs) impacted sites with concentrations ranging from 0.05 to 2.18 µg/L in water and from not detected - 9.67 µg/g in periphyton. Regarding community structure, the occurrence of macrolides was negatively linked to FirmicutesExiguobacterium undae and Exiguobacterium sibiricum, CyanobacteriaOscillatoriales and Vischeria sp., and ChlorophytaMonostroma grevillei, Selenastrum sp. LU21 and Desmodesmus subspicatus. At the functional level, only the metabolism of phenolic acids was significantly decreased in river reach with high antibiotic levels in June, compared to the other five carbon sources that were not altered. The overall photosynthetic activity of periphytic photosystem II remained unchanged in both reference and STPs impacted groups throughout three seasons. Overall, the macrolides released from STPs were correlated with the altered periphytic structures in the river, whereas a similar trend was not detected for the community functions owing to the functional redundancy. A mesocosm experiments warrants further consideration to validate the field results.

Sonographic features of Lemmel's syndrome: Differential diagnosis from stones in the lower portion of the common bile duct.

BACKGROUND AND STUDY AIMS: Periampullary diverticula (PAD), a location-specific type of duodenal diverticula, can cause serious complications. PAD is difficult to differentially diagnose, mainly due to its nonspecific symptoms. This study aimed to identify sonographic features of PAD and to evaluate their value in the differential diagnosis of PAD from stones in the lower common bile duct (CBD). PATIENTS AND METHODS: A total of 30 patients with PAD and 60 patients with lower CBD stones were retrospectively enrolled, and sonographic features were analyzed. Measurements of sonographic features included echo shaped, posterior echo changes, location and relation to surrounding organs, and status of intrahepatic and extrahepatic bile duct dilation, and their diagnostic performance was assessed. RESULTS: Characteristic sonographic features of PAD were identified, including strong echoes (28/30, 93.3 %), strip shape (28/30, 93.3 %), multiple reflections in the posterior echo (27/30, 90.0 %), and location outside the CBD or near the biliary wall in connection with the duodenum (27/30, 90.0 %). Inter-observer agreement was good (Kappa values = 0.69-0.82). Comparative analysis of sonographic features revealed significant differences in echo shape, posterior echo changes (multiple reflections and acoustic shadowing), location and relation to surrounding organs, and intrahepatic and extrahepatic bile duct dilatation status between the dilatation status of the two groups. In particular, these characteristics achieved a sensitivity of 100 % and a specificity of 98 % for the differential diagnosis of PAD and lower CBD stones. CONCLUSIONS: This study identified characteristic sonographic features of PAD, which could be used as potential diagnostic indicators to distinguish PAD from lower CBD stones.

Extended Paid Maternity Leave Associated With Improved Maternal Mental Health In Hong Kong.

In July 2020, Hong Kong extended statutory paid maternity leave from ten weeks to fourteen weeks to align with International Labour Organization standards. We used the policy enactment as an observational natural experiment to assess the mental health implications of this policy change on probable postnatal depression (Edinburgh Postnatal Depression Scores of 10 or higher) and postpartum emotional well-being. Using an opportunistic observational study design, we recruited 1,414 survey respondents with births before (August 1-December 10, 2020) and after (December 11, 2020-July 18, 2022) policy implementation. Participants had a mean age of thirty-two, were majority primiparous, and were mostly working in skilled occupations. Our results show that the policy was associated with a 22 percent decrease in mothers experiencing postnatal depressive symptoms and a 33 percent decrease in postpartum emotional well-being interference. Even this modest change in policy, an additional four weeks of paid leave, was associated with significant mental health benefits. Policy makers should consider extending paid maternity leave to international norms to improve mental health among working mothers and to support workforce retention.

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.

Contact to perfluoroalkyl substances and thyroid health effects: A meta-analysis directing on pregnancy.

In vivo, in vitro, and epidemiological evidence suggests that perfluoroalkyl substances (PFAS) may alter thyroid function in human health, with negative effects on maternal and fetal development outcomes. However, data on the effects of PFAS on thyroid hormones remain controversial. Here, we conducted a meta-analysis of 13 eligible studies searched from Embase, PubMed, and Web of Science by July 10, 2022, to explore the relationship between maternal exposure to PFAS and thyroid health effects, including thyroid stimulating hormone (TSH), triiodothyronine (TT3), thyroxin (TT4), free T3 (FT3), and free T4 (FT4). The estimated values (ß) and the corresponding confidence intervals (95%CI) were extracted for analysis. The tests for heterogeneity, sensitivity and publication bias between studies were performed using Stata 15.0. The combined results showed a positive association between changes in TSH and exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), with no significant correlation observed between changes in other thyroid hormones and exposure to PFAS. This difference was attributed to sample size, region, sample type, body mass index (BMI), and gestational week. Our data recommend verifying the relationship between PFAS exposure and thyroid health effects in a large sample population cohort in future studies. In addition, health care should be taken into account in early and mid-pregnancy.

Whole Grain Proso Millet (Panicum miliaceum L.) Attenuates Hyperglycemia in Type 2 Diabetic Mice: Involvement of miRNA Profile.

This work aimed to investigate the hypoglycemic effects and underlying mechanism of whole grain proso millet (Panicum miliaceum L.; WPM) on type 2 diabetes mellitus (T2DM). The results showed that WPM supplementation significantly reduced fasting blood glucose (FBG) and serum lipid levels in T2DM mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ), with improved glucose tolerance, liver and kidney injury, and insulin resistance. In addition, WPM significantly inhibited the expression of gluconeogenesis-related genes G6pase, Pepck, Foxo1, and Pgc-1α. Further study by miRNA high-throughput sequencing revealed that WPM supplementation mainly altered the liver miRNA expression profile of T2DM mice by increasing the expression of miR-144-3p_R-1 and miR-423-5p, reducing the expression of miR-22-5p_R-1 and miR-30a-3p. GO and KEGG analyses showed that the target genes of these miRNAs were mainly enriched in the PI3K/AKT signaling pathway. WPM supplementation significantly increased the level of PI3K, p-AKT, and GSK3ß in the liver of T2DM mice. Taken together, WPM exerts antidiabetic effects by improving the miRNA profile and activating the PI3K/AKT signaling pathway to inhibit gluconeogenesis. This study implies that PM can act as a dietary supplement to attenuate T2DM.