Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma.

BACKGROUND: The incidence of primary liver cancer is increasing year by year. In 2022 alone, more than 900000 people were diagnosed with liver cancer worldwide, with hepatocellular carcinoma (HCC) accounting for 75%-85% of cases. HCC is the most common primary liver cancer. China has the highest incidence and mortality rate of HCC in the world, and it is one of the malignant tumors that seriously threaten the health of Chinese people. The onset of liver cancer is occult, the early cases lack typical clinical symptoms, and most of the patients are already in the middle and late stage when diagnosed. Therefore, it is very important to find new markers for the early detection and diagnosis of liver cancer, improve the therapeutic effect, and improve the prognosis of patients. Protein tyrosine phosphatase non-receptor 2 (PTPN2) has been shown to be associated with colorectal cancer, triple-negative breast cancer, non-small cell lung cancer, and prostate cancer, but its biological role and function in tumors remain to be further studied. AIM: To combine the results of relevant data obtained from The Cancer Genome Atlas (TCGA) to provide the first in-depth analysis of the biological role of PTPN2 in HCC. METHODS: The expression of PTPN2 in HCC was first analyzed based on the TCGA database, and the findings were then verified by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting. The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features. Finally, the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining. RESULTS: The results of immunohistochemical staining, qRT-PCR, and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways, including cancer-related pathways, the Notch signaling pathway, and the MAPK signaling pathway. Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways, such as the epithelial mesenchymal transition process. A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group. CONCLUSION: This study investigated PTPN2 from multiple biological perspectives, revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Lack variation of low slow-wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease.

OBJECTIVE: Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. METHODS: We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. RESULTS: Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. CONCLUSION: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

White Matter Hyperintensities and Cognitive Functions in People With the R544C Variant of the NOTCH3 Gene Without Stroke or Dementia.

BACKGROUND AND OBJECTIVES: NOTCH3 pathologic variants cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which presents with stroke and dementia and is characterized by white matter hyperintensities (WMHs) on brain MRI. The R544C variant is a common pathologic variant in Taiwan, but not all carriers exhibit significant symptoms. We investigated whether WMHs occur before clinical symptoms in carriers with pathogenic variants, examined factors associated with WMHs, and explored their relationship with cognitive functions. METHODS: We enrolled 63 R544C carriers without overt clinical disease (WOCD) and 37 age-matched and sex-matched noncarriers as controls from the Taiwan Precision Medicine Initiative data set. All participants underwent clinical interviews, comprehensive neuropsychological assessments, and brain MRI. We calculated total and regional WMH volumes, determined the age at which WMHs began increasing in carriers, and examined the relationship between WMHs and neuropsychological performance. Factors associated with WMH volumes were analyzed using multivariable linear regression models. RESULTS: Compared with controls, R544C carriers WOCD had increased WMH volume, except in the occipital and midbrain areas, and showed a rapid increase in WMHs starting at age 48. They scored lower on the Mini-Mental State Examination (median = 28.4 vs 29.0, p = 0.048), Montreal Cognitive Assessment (MoCA) (median = 28.3 vs 29.0, p = 0.013), and memory and executive function tests than controls. After adjusting for age, sex, and education, MoCA scores were associated with whole-brain (r = -0.387, padj = 0.008) and regional WMHs (all padj < 0.05) except in the midbrain area. Age (ß = 0.034, 95% CI 0.021-0.046, p < 0.001), hypercholesterolemia (ß = 0.375, 95% CI 0.097-0.653, p = 0.009), and the vascular risk factor (VRF) index (ß = 0.132, 95% CI 0.032-0.242, p = 0.019) were associated with the WMH severity in carriers. DISCUSSION: Our study revealed that WMHs are extensively distributed in R544C carriers WOCD. They exhibited a rapid increase in WMHs beginning at age 48, approximately 7 years earlier than the reported age at symptomatic onset. Age was the strongest predictive factor of WMHs, and VRF, particularly hypercholesterolemia, might be modifying factors of WMHs.

A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia.

Mutations in the well-known Myostatin (MSTN) produce a 'double-muscle' phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant 'double-muscle' phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation.

Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

Bidirectional enhancement of output performance of nanogenerators by M-COFs materials.

The emergence of nanogenerators, which have the ability to capture mechanical energy from the environment and to collect and transmit tiny energy, is rapidly becoming a hot research topic. The performance of electrode materials is the key to the efficiency of nanogenerators. Covalent organic skeletons (COFs), a class of crystalline organic porous materials with the advantages of large specific surface area, high porosity, tunable structure, and flexible tailorability, have very significant advantages in being used as nanogenerator materials. In this paper, we synthesised two COF materials to investigate the effect of the introduction of active metals on the friction power generation performance of COFs without changing their topology, COF-2 containing zinc ions is capable of generating a short-circuit current of 107.5 µA during friction. The porous structure increases the effective contact area to form a larger charge density, and the introduction of metal ions can accelerate the charge separation and transport. The two bidirectional synergistic effects of the materials significantly improve the output performance of the nanogenerator, and a simple and efficient method is explored for the enhancement of the output performance of COF-based triboelectric nanogenerators.

The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.

In cancer research, RAS biology has been focused on only a handful of tumor types. While RAS genes have long been suspected as common contributors to a wide spectrum of cancer types, robust evidence is required to firmly establish their critical oncogenic significance. We present a data mining study using DepMap genome-wide CRISPR screening data, which provide substantial evidence to support the prominent pervasive oncogenic role and tissue-specific permissiveness of RAS gene mutations. Differential analysis of CRISPR effect scores identifies K- or N-RAS genes as the most differential gene in contrasts of (K-, N-, combined) RAS mutant versus wild-type cell lines across multiple tissue types. The distinguished tissue-specific pattern of KRAS vs. NRAS as top differential genes in subsets of tissue types and evidence from genome data supported the idea of KRAS- and NRAS-engaged tissue types. To our knowledge, this is the first report of prominent pervasive oncogenic role of RAS mutations revealed by gene dependency data that is beyond the current understanding of the oncogenic role of RAS genes and their well-known involved tissue types. Our findings strongly support RAS mutations as primary oncogenic drivers beyond traditionally recognized cancer types and offer insights into their tissue-specific permissiveness.

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 µg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 µg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 µg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 µg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 µg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

Superior cervical ganglionectomy attenuates vascular remodeling in spontaneously hypertensive rats.

BACKGROUND: Sympathetic hyperactivity contributes to the pathogenesis of hypertension. However, it is unclear whether the excessive sympathetic activity is an independent and crucial factor for vascular remodeling in hypertension. This study focused on the effect of local sympathetic denervation with superior cervical ganglionectomy (SCGx) on vascular remodeling. METHODS: Surgical bilateral SCGx was performed in 9-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Control rats received sham-operation without SCGx. All measurements were made 4 weeks after the surgery. RESULTS: The effectiveness of SCGx was confirmed by the eye features of Horner syndrome, greatly reduced tyrosine hydroxylase (TH) contents in the superior cervical ganglion (SCG)-innervated arteries in the head. Although SCGx had no significant effects on blood pressure and heart rate in WKY and SHR, it attenuated vascular remodeling of facial artery and superficial temporal artery in SHR, two representative SCG-innervated extracranial arteries, without significant effects on non-SCG-innervated thoracic aorta and mesenteric artery. SCGx-treated SHR had more auricular blood flow and retina microvasculature than sham-operated SHR. However, SCGx had only a mild effect in attenuating the vascular remodeling of basilar artery and middle cerebral artery, two representative SCG-innervated intracranial arteries, in SHR. SCGx-treated SHR exhibited upregulation of α-smooth muscle actin, downregulation of proliferating cell nuclear antigen, and attenuation of oxidative stress and inflammation in facial artery and superficial temporal artery. CONCLUSIONS: Sympathetic denervation by SCGx in SHR attenuated local vascular remodeling, suggesting that sympathetic overactivity is a crucial pathogenic factor of vascular remodeling in SHR.

Is pancreaticoduodenectomy justified for metastatic melanoma to the ampulla of Vater?

BACKGROUND: Metastatic melanoma of the ampulla of Vater is rare. The purpose of this study was to summarize the characteristics and outcomes of metastatic melanoma in the ampulla of Vater and highlight the impact of surgery on the prognosis of patients with metastatic melanoma. METHODS: Pooled data from a case encountered at our institution and from all sporadic cases published on PubMed and MEDLINE between 1996 and 2023 were analyzed. RESULTS: Fourteen patients with metastatic melanoma in the ampulla of Vater were enrolled. Seventy-three percent of primary melanomas were cutaneous and 27% were mucosal. Jaundice was the most common symptom (86%). The size of metastatic melanoma to the ampulla ranged from 1.5 cm to 8 cm, with a median of 2.75 cm. Concomitant metastasis to other organs occurred in 82% of the patients at the time of diagnosis, most commonly in the brain, lungs, and liver (36% each). Among the reported cases, pancreaticoduodenectomy was performed in five patients. The overall 1-year survival rate was 27.3%, with a median survival of four months. Wide excision of the primary lesion and chemotherapy significantly improved survival rates (p= 0.048). There is a trend toward improved survival in patients undergoing pancreaticoduodenectomy followed by chemotherapy. CONCLUSION: Given the availability of effective systemic therapies, metastatic melanoma of the ampulla of Vater does not necessarily preclude major surgeries.

Anti-peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as potential predictors of good response to tofacitinib therapy in rheumatoid arthritis patients.

OBJECTIVES: To maximize the cost-effectiveness of tofacitinib, one of Janus kinase inhibitors, there is an unmet need to identify predictors of therapeutic response. Utilizing phage immunoprecipitation sequencing (PhIP-Seq), we aim to identify peptide biomarkers for predicting good response to tofacitinib in rheumatoid arthritis (RA) patients. METHODS: We enrolled 106 patients who had received 24-week tofacitinib therapy, including twelve patients undergoing PhIP-Seq analysis in the discovery stage and ninety-four patients validated with enzyme-linked immunosorbent assay (ELISA) in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate, and therapeutic response was evaluated using EULAR response criteria. Plasma levels of caspase-1 and IL-18 were determined using ELISA. RESULTS: PhIP-Seq analysis identified antibodies to sucrose non-fermenting-related kinase (SNRK) and HUWE1 (ubiquitin E3 ligase) as peptide biomarkers for discriminating good responders from the non-good responders. Using ELISA for validation on another cohort, an optimal cut-off value of anti-SNRK antibody for predicting good response was 0.381, with AUC 0.823, specificity 80.6%, and sensitivity 78.1% (p = 3.01E-07), and anti-HUWE1 antibody at 0.362, with AUC 0.740, specificity 74.2%, and sensitivity 62.5% (p < 0.001). Plasma levels of anti-SNRK and anti-HUWE1 antibodies were positively correlated with levels of caspase-1 and IL-18 (both p < 0.05). Multivariate logistic regression analysis revealed anti-SNRK antibody as a significant predictor of good therapeutic response. After tofacitinib therapy, anti-SNRK antibody levels significantly declined in good responders, but not in non-good responders. CONCLUSION: We identify two peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as pretreatment predictors of good therapeutic response to tofacitinib in RA patients.

In utero and childhood exposure to the great Chinese famine and risk of aging in adulthood.

Background Early-life exposure to famine may influence the occurrence of chronic diseases and aging in midlife among those exposed. This study aims to explore the relationship between exposure to the Chinese Great Famine and aging in middle-aged individuals. Methods Participants born in 1963-1965 (unexposed), 1959-1961 (in utero exposure), and 1955-1957 (childhood exposure) from the Kailuan Study were included. Their biological age at 2010, 2014, and 2018 was investigated, and age acceleration (biological age minus actual age) was calculated to assess aging. Logistic regression analysis was employed to describe the relationship between famine exposure and the aging risk. Subgroup and sensitivity analysis were conducted to explore differences and stability in this relationship among different groups. Results A total of 17,543 participants were included in this study. Among them, 12,762 (72.7%) were male, and 4,781 (27.3%) were female, with 2,543 participants experiencing aging events. Compared to unexposed participants, those exposed during childhood and in utero exhibited a 1.69-fold (OR = 1.69, 95%CI: 1.53-1.87) and 1.22-fold (OR = 1.22, 95%CI: 1.08-1.37) increased risk of aging. Subgroup analysis revealed an interaction with income (P for interaction = 0.008), and additional interaction analysis suggested that increasing income could partially mitigate the detrimental effects of early-life famine exposure. Furthermore, experiencing famine in severely affected regions exacerbated the risk of aging (OR = 1.41, 95%CI: 1.21-1.63). Conclusion Exposure to famine in utero or during childhood may elevate the risk of midlife aging among exposed individuals, and these relationships are influenced by the severity of famine exposure. Increasing income may also help mitigate these effects.Trial registration: Kailuan study, ChiCTRTNRC11001489. Registered July 19, 2015 Retrospectively registered, https//www.chictr.org.cn/showprojEN.html?proj=8050&u_atoken=af46a0dee8d73f320bb5459ab7bbcfa9&u_asig=1a0c381017255295896468605e00cf .

ARL8B promotes hepatocellular carcinoma progression and inhibits antitumor activity of lenvatinib via MAPK/ERK signaling by interacting with RAB2A.

Tumor recurrence and metastasis are important factors affecting postoperative survival in hepatocellular carcinoma (HCC) patients. ADP Ribosylation factor-like GTPase 8B (ARL8B) plays a crucial role in many biological processes, including lysosomal function, immune response, and cellular communication, all of which are related to the occurrence and development of tumors. However, its role in HCC remains unclear. Herein, we revealed that ARL8B is consistently elevated in HCC tissues compared to normal liver tissues, suggesting an unfavorable outcome in HCC patients. Increased ARL8B levels promoted the malignant phenotype of HCC in vitro and in vivo. Notably, ARL8B also induced epithelial-to-mesenchymal transition (EMT) in HCC cells. Mechanistically, the results of bioinformatics analysis combined with mass spectrometry revealed the potential downstream target molecule RAB2A of ARL8B. ARL8B directly interacted with RAB2A and increased the levels of GTP-bound RAB2A, thereby contributing to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Interestingly, knockout of ARL8B in Hep3B cells enhanced the antitumor activity of lenvatinib in vitro and in vivo. Furthermore, AAV-shARL8B enhanced the inhibition of HCC growth through lenvatinib, providing new insights into its mechanism of action in lenvatinib-insensitive patients. In conclusion, ARL8B promotes the malignant phenotype of HCC and EMT via RAB2A mediated activation of the MAPK/ERK signaling pathway and is expected to be a valuable prognostic indicator and therapeutic target for HCC patients.

DNA hypermethylation of COL4A1 in ultraviolet-B-induced age-related cataract models in vitro and in vivo.

AIM: To explore the DNA methylation of COL4A1 in ultraviolet-B (UVB)-induced age-related cataract (ARC) models in vitro and in vivo. METHODS: Human lens epithelium B3 (HLEB3) cells and Sprague Dawley rats were exposure to UVB respectively. The MTT assay was utilized to evaluate cell proliferation. Flow cytometry was employed for analysis of cell apoptosis and cell cycle. COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence. The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR (BSP). DNMTs and TETs mRNA levels was examined by RT-PCR. RESULTS: UVB exposure decreased HLEB3 cells proliferation, while increased the apoptosis rate and cells were arrested in G0/G1 phase. COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls. Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure. Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls, while expressions of TETs including TET1/2/3 showed the opposite trend. Results from the UVB treated rat model further confirmed the decreased expression of COL4A1, hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group. CONCLUSION: DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

Accuracy and validation of a point-of-care blood glucose monitoring system for use in horses.

Abnormal blood glucose (BG) levels often seen in critically ill horses are significantly associated with adverse patient outcomes and increased mortality. Rapid and accurate BG monitoring is now considered an essential component of evidence-based equine practice and can provide critical information quickly for treatment. Although several point-of-care (POC) BG monitoring hand-held devices are commercially available for veterinary use, none contains a unique algorithm validated for use in horses. The AlphaTrak 3 (AT3) BG monitoring system is a first-of-its-kind device with an equine-specific algorithm that allows stall-side clinical decision making, and frequent monitoring at minimal cost. As such, AT3 is potentially a preferred alternative to more costly and time-consuming standard diagnostic reference laboratory methods. The objective of this study was to determine the accuracy of the AT3 device in measuring BG levels in equine whole blood samples in comparison to results obtained by the Beckman Coulter AU480 reference analyzer per ISO15197:2013 specifications. Accuracy of the AT3 equine algorithm were initially verified by testing equine blood samples with artificially adjusted blood glucose levels followed by its validation in a field study. Testing with artificially adjusted equine samples (n = 129) showed that 98.9% of glucose measurements ranging from 29 to 479 mg/dL fell within ISO accuracy threshold of ±15 mg/dL or ±15% of the average reference value. In addition, 100% of the AT3 measurements fell in consensus error grid (CEG) zone A, which indicates that test outcomes have a minimal likelihood of adverse clinical impact. In a follow-up field study involving 96 horses, 98.4% of AT3 measurements met the ISO accuracy threshold and 99.2% of AT3 measurements fell in CEG zone A. These results demonstrate that the AT3 glucometer has a high degree of accuracy in horses and is a dependable, convenient, and cost-effective device for accurately monitoring equine BG levels in farm or clinical settings.

Association between weekend catch-up outdoor duration and prevalence of myopia: evidence from a cross-sectional, multi-center study in China.

BACKGROUND: This study aimed at investigating the relationship between the weekend catch-up outdoor duration (WCOD) and prevalence of myopia among students in China. METHODS: This cross-sectional study recruited participants in 107 schools (six cities, 30 districts) from China from May to June 2021. Demographic characteristics (age, grade, sex, ethnicity, BMI, resident, and parents' myopia), optically habits (bad writing habits, working/studying time per day, continuous working/studying time per day, and screen time per day) and outdoor duration (weekday and weekend) were obtained from questionnaire. WCOD was defined as outdoor time 1 h longer on weekends than on weekdays. Spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Adjusted multivariate logistic regression analysis was performed to evaluate the relationship between WCOD and prevalence of myopia. RESULTS: Students with myopia had shorter WCOD compared with those without myopia (P < 0.001). Adjusted multivariate logistic regression analyses showed negative associations between WCOD and prevalence of myopia in Chinese students, especially in students with WCOD of 2-3 h (OR = 0.577, P < 0.001) and 3-4 h (OR = 0.571, P = 0.004) when the weekday outdoor duration was 0.5-1 h, as well as students with WCOD of 2-3 h (OR = 0.614, P = 0.003) when the weekday outdoor duration was 1-2 h. Similar results were observed in students with high myopia. Students with high myopia had shorter WCOD compared with those without high myopia (P = 0.001). Negative associations between WCOD and prevalence of high myopia were significant in students with WCOD of 1-2 h when the weekday outdoor duration was < 0.5 h (OR = 0.585, P = 0.007) and 0.5-1 h (OR = 0.537, P = 0.018). CONCLUSION: Our study, for the first time, reported that a WCOD have a potential to reduce the prevalence of myopia and high myopia in Chinese students.

Cardiovascular toxicity of anaplastic lymphoma kinase inhibitors for patients with non-small cell lung cancer: a network meta-analysis.

Aim: We conducted network meta-analysis to assess cardiovascular toxicity of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs).Materials & methods: Eleven articles involving 2855 patients and six interventions including crizotinib, alectinib, ceritinib, lorlatinib, brigatinib and chemotherapy were analyzed.Results: No significant difference was observed in overall cardiovascular risk among ALK-TKIs. Subgroup analysis showed that for cardiac toxicity, crizotinib and alectinib were more likely to cause myocardial rhythm abnormalities. Crizotinib and ceritinib had a higher risk of Q-T prolongation than chemotherapy. For vascular toxicity, crizotinib and ceritinib had a higher risk of thrombotic events than brigatinib. Crizotinib and lorlatinib were more likely to cause blood pressure abnormalities.Conclusion: Clinicians should carefully monitoring cardiovascular events when ALK-TKIs used in NSCLCs patients with baseline cardiovascular diseases.

A network meta-analysis revealed the cardiovascular toxicity caused by ALK-TKIs in non-small cell lung cancer patients.

Effects of straws on greenhouse gas emissions in the ectopic fermentation system.

Straws are commonly used padding materials in the ectopic fermentation system, but their effects on greenhouse gas emissions are not well understood. This study compared the effects of rape, rice and corn straws on the fermentation performance of the ectopic fermentation system. Compared with corn straw, the treatment groups with rape straw and rice straw significantly increased the alpha diversity of the fermentation system, and simultaneously mitigated the cumulative emissions of CO2 and N2O by up to 32.4% and 93.9%, respectively. The CO2 and N2O peak emission in the treatment group with corn straw reached 1.4 × 106 and 36.2 mg/m2/d, respectively. CH4 peak emission was one order of magnitude lower than that of N2O in the ectopic fermentation system. Redundancy analysis showed that Pseudoxanthomonas sp000510725 was the key specie that positively affect the fermentation temperature, CO2 and N2O emissions in the fermentation system. Nitrogen metabolism genes, such as nosZ, nirK, and nirS were more abundant in the surface layer of the fermentation system, indicating more active nitrogen metabolism in this region, and the core zone could be the primary source of N2O emissions. Those findings indicated that rape and rice straw can be potential padding materials for mitigating greenhouse gas emissions in large-scale ectopic fermentation system.

Astrocytic lactoferrin deficiency augments MPTP-induced dopaminergic neuron loss by disturbing glutamate/calcium and ER-mitochondria signaling.

Increased levels of lactoferrin (Lf) are present in the aged brain and in the lesions of various neurodegenerative diseases, including Parkinson's disease (PD), and may contribute to the cascade of events involved in neurodevelopment and neuroprotection. However, whether Lf originates from astrocytes and functions within either the normal or pathological brain are unknown. Here, we employed mice with specific knockout of the astrocyte lactoferrin gene (named Lf-cKO) to explore its specific roles in the pathological process of PD. We observed a decrease in tyrosine hydroxylase-positive cells, mitochondrial dysfunction of residual dopaminergic neurons, and motor deficits in Lf-cKO mice, which were significantly aggravated after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. To further explore how astrocytic lactoferrin deficiency exacerbated PD-like manifestation in MPTP-treated mice, the critical molecules involved in endoplasmic reticulum (ER)-mitochondria contacts and signaling pathways were investigated. In vitro and in vivo models, we found an aberrant level of effects implicated in glutamate and calcium homeostasis, mitochondrial morphology and functions, mitochondrial dynamics, and mitochondria-associated ER membranes, accompanied by signs of oxidative stress and ER stress, which increase the fragility of dopaminergic neurons. These findings confirm the existence of astrocytic Lf and its influence on the fate of dopaminergic neurons by regulating glutamate/calcium metabolism and ER-mitochondria signaling. Our findings may be a promising target for the treatment of PD.

Relationship between left atrial isolated surface area and early-term recurrence in patients with persistent atrial fibrillation after cryoballoon ablation.

OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.