PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.

Pyruvate dehydrogenase kinase 1 (PDK1) phosphorylates the pyruvate dehydrogenase complex, which inhibits its activity. Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis, which plays an important role in tumor progression. This study aims to elucidate how PDK1 promotes breast cancer progression. We found that PDK1 was highly expressed in breast cancer tissues, and PDK1 knockdown reduced the proliferation, migration, and tumorigenicity of breast cancer cells and inhibited the HIF-1α (hypoxia-inducible factor 1α) pathway. Further investigation showed that PDK1 promoted the protein stability of HIF-1α by reducing the level of ubiquitination of HIF-1α. The HIF-1α protein levels were dependent on PDK1 kinase activity. Furthermore, HIF-1α phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells. The phosphorylation of HIF-1α at Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1α with von Hippel-Lindau and prolyl hydroxylase domain. We also found that PDK1 enhanced HIF-1α transcriptional activity. In summary, PDK1 enhances HIF-1α protein stability by phosphorylating HIF-1α at Ser451 and promotes HIF-1α transcriptional activity by enhancing the binding of HIF-1α to P300. PDK1 and HIF-1α form a positive feedback loop to promote breast cancer progression.

Characteristics and scoring method of computed tomography in open-globe injuries.

BACKGROUND: Open-globe injuries (OGIs) remain the important cause of visual impairment and loss in all ages. Computed Tomography (CT) is a useful and common tool in the evaluation of the injuries of the eyeball. Prognostic value of CT scan in OGIs has been evaluated in many studies. However, there is no published consistent systematic scoring method for CT scan in OGIs. The purpose of this study was to evaluate the CT characteristics of OGIs and build a scoring method according to the CT scans which may aid the clinicians in management of OGIs. METHODS: Retrospective chart review of inpatients with clinical diagnosis of OGIs between 2017 and 2021 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital (Zhengzhou, China). RESULTS: There were 1120 eyes from 1117 patients included in our study. The mean age was 35.7 ± 21.9 years with the range from 1 to 91 years. Significant male predominance was noted (889, 79.6%). CT scans of the OGIs were evaluated. Abnormality of anterior segment, posterior segment, and globe contour and volume were graded respectively. The most serious abnormality of anterior segment, posterior segment, and globe contour and volume were grade 3, 4 and 3 respectively and score 3, 4 and 3 respectively. Score of the CT scans of an open-injured globe ranged from 0 to 10. The correlation coefficient between the score and wound length was 0.798. The correlation coefficient between the score and final visual acuity was 0.799. In 78 eyes with 0 score, 70 eyes (89.7%) gained final visual acuity of 0.3 or better. In 31 eyes with 10 score, 20 eyes (64.5%) underwent evisceration of the eye globe and 10 eyes got visual acuity of no light perception and 1 eye lost to follow-up. CONCLUSIONS: CT scans is a useful tool in evaluating the severity of an open-injured globe. Scoring of the CT scans of an open-injured globe is a meaningful attempt and it may provide useful prognostic information regarding the outcome of an open-injured globe.

AURKA inhibition induces Ewing's sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis.

Ewing's sarcoma (ES) is a rare and highly aggressive malignant tumor arising from bone and soft tissue. Suffering from intractable or recurrent diseases, the patients' therapy options are very limited. It is extremely urgent to identify novel potential therapeutic targets for ES and put them into use in clinical settings. In the present study, high-throughput screening of a small molecular pharmacy library was performed. The killing effect of the Aurora kinase A (AURKA) inhibitor TCS7010 in ES cells was identified, and AURKA was selected as the research object for further study. Disparate suppressants were adopted to study the cell death manner of TCS7010. TCS7010 and RNA silencing were used to evaluate the functions of AURKA in the apoptosis and ferroptosis of ES cells. Co-immunoprecipitation assay was used to investigate the correlation of AURKA and nucleophosmin1 (NPM1) in ES. Nude-mice transplanted tumor model was used for investigating the role of AURKA in ES in vivo. Investigations into the protein activities of AURKA were conducted using ES cell lines and xenograft models. AURKA was found to be prominently upregulated in ES. The AURKA expression level was remarkably connected to ES patients' shorter overall survival (OS) and event-free survival (EFS). Furthermore, AURKA inhibition markedly induced the apoptosis and ferroptosis of ES cells and attenuated tumorigenesis in vivo. On the part of potential mechanisms, it was found that AURKA inhibition triggered the apoptosis and ferroptosis of ES cells through the NPM1/Yes1 associated transcriptional regulator (YAP1) axis, which provides new insights into the tumorigenesis of ES. AURKA may be a prospective target for clinical intervention in ES patients.

Multibranched Molecule Defoamers Based on Methyl Gallate for Highly Effective Defoaming and Antifoaming.

Bubbles or foams appear in many industrial processes, bringing inconvenience; yet, efficient capture or removal of them is still challenging. In this study, we report the synthesis and properties of multibranched molecule defoamers based on methyl gallate derivatives (Mb-GDs), which adopt methyl gallate (M-G) as the parent structure, by incorporating alkyl groups from alkyl isocyanates (A-I) with different chain lengths (C12 and C18) to replace R-OH in the M-G structure and further by linking two Mb-GDs into one Gemini-type multibranched derivative (Gt-Mb-GD) by transesterification to construct a defoamer material with a larger spatial volume. The surface properties and interfacial activity of molecular defoamers in aqueous solutions were studied, and the structure-property relationships of the multibranched gallate molecule defoamers based on Mb-GDs and Gt-Mb-GDs were further investigated by comparing the defoaming and antifoaming performance in four typical surfactant foams and foaming solutions with two kinds of commercial defoamers. The foam experiments indicated that the defoamers with a longer branched chain length (C18) showed more effectiveness in defoaming and antifoaming for four surfactant foams or foaming solutions, even at very low dosages, which were far stronger than the commercial high-carbon alcohol defoamer with a linear structure and comparable to branched silicone-based emulsion-type defoamers. Compared with Mb-GD defoamers, Gt-Mb-GD defoamers with a larger branched structure showed a higher defoaming performance. The study found the great potential of materials with multibranched structures for practical applications as the core components of high-performance defoamers.

Construction of high-branched derivatives based on melamine for highly effective defoaming and antifoaming.

Foams can be seen everywhere in human production and life. An uncontrolled foam event usually leads to product losses, equipment damage, and clean-up costs. Defoamer is one of the most effective strategies to eliminate or inhibit foam activities, which has been proved by long-term practices. In this work, we report new molecular defoamers with high-branched structure, which adopts melamine molecule as the parent structure, by incorporating alkyl-isocyanates with different chain lengths into the high-branched melamine derivatives (Hb-MDs) formula to replace the R - NH2 (primary ammonia) on melamine structure. The substitution reaction processes can be readily tuned by varying the molar ratio or alkyl chain length of alkyl-isocyanate, enabling a facile control over the branched degree. The foam tests reveal that the high-branched melamine molecule defoamers exhibited excellent defoaming and anti-foaming properties for four typical foam systems, including an anionic SDBS, cationic DTAB, non-ionic AEO-9, and white cat (BM) detergent, with efficiency close to that of silicone-type LN1414 defoamer and far superior to that of high-carbon alcohol XS-02 defoamer, at the same addition level. Notably, the defoaming or anti-foaming performances of the high-branched melamine molecule defoamers were not always monotonically increased with the branched degree or hydrophobic chain length, but a suitable range needed to be maintained to support a good balance of defoamer structure with foam liquid films. Therefore, it is anticipated that this high-branched design principle could open a new avenue for the construction of molecular defoamers for complex industrial problems.

The role of cognitive function in the relationship between surrogate markers of visceral fat and depressive symptoms in general middle-aged and elderly population: A nationwide population-based study.

BACKGROUND: The relationship between obesity and depressive symptoms is well documented, but not visceral fat, especially among Chinese adults are scarce. We aimed to investigate the association between visceral fat and depressive symptoms and the mediation of cognitive function. METHODS: A total of 19,919 and 5555 participants from the China Health and Retirement Longitudinal Study were enrolled in the cross-sectional and follow-up analyses. Depressive symptoms were measured by the Center of Epidemiological studies depression scale (CES-D). Visceral fat measured by the waist circumference triglyceride (WT) index [calculated as waist circumference (cm)* triglyceride (mmol/L)]. The relationship between the WT index and depressive symptoms was analyzed by binary logistics and Poisson regression. The mediated role of cognitive ability was examined by intermediary analysis. RESULTS: In the cross-sectional study, higher visceral fat was associated with a lower risk of depressive symptoms. But in the follow-up study, individuals in quintile 2 to quintile 4 of the WT index have a reduced risk of depressive symptoms after four years. Compared with the lower index, quintile 2 of the WT index protected from difficulty concentrating (RR [95%CI]: 0.90 [0.82,0.98], p = 0.023), feeling scared (RR [95%CI]: 0.86 [0.73,0.98], p = 0.030) and feeling that life could not go on (RR [95%CI]: 0.85 [0.74,0.98], p = 0.023). Moreover, cognitive ability explained 11.52 % of the association between visceral fat and depressive symptoms. CONCLUSIONS: Our findings show that moderate visceral fat was associated with a lower risk of depressive symptoms in middle-aged and older Chinese, partly mediated by cognitive function.

GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer.

Background: Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated. Methods: In this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown. Results: GNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells. Conclusion: GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.

PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1 in the nucleus and significantly enhanced the stability of SRPY4-IT1. Furthermore, SPRY4-IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

The association between longitudinal changes in depressive symptoms and cognitive decline among middle-aged and older Chinese adults.

OBJECTIVE: Depression is associated with cognitive impairment and dementia, but few studies have been done on Chinese adults. This study evaluates the relationship between depressive symptoms status and cognitive function in middle-aged and elderly Chinese adults. METHODS: We included 7,968 participants from the Chinese Health and Retirement Longitudinal Survey (CHRALS) with a follow-up of 4 years. Using the Center for Epidemiological Studies Depression Scale to measure depressive symptoms, with a score of 12 or more indicating elevated depressive symptoms. Adjust covariance analysis and generalized linear analysis were used to investigate the relationship between depressive symptoms status (never, new-onset, remission and persistence) and cognitive decline. Restricted cubic spline regression was used to performed the potential nonlinear associations between depressive symptoms and the change scores of cognitive functions. RESULTS: During the 4-year follow-up, 1148 participants (14.41%) reported persistent depressive symptoms. The participants who have persistent depressive symptoms with more declines in total cognitive scores (least-square mean = -1.99, 95% CI: -3.70 to -0.27). Compared with never depressive symptoms, participants with persistent depressive symptoms experienced a faster decline in cognitive scores (ß = -0.68, 95%CI: -0.98 to -0.38), and small difference (d=0.29) at follow-up. But females with new-onset depression had more cognitive decline than those with persistent depression (least-square mean new-onset - least-square mean persistent=-0.10), its differences in males (least-square mean new-onset - least-square mean persistent=0.03). CONCLUSIONS: Participants with persistent depressive symptoms experienced a faster decline in cognitive function, but differently in men and women.

Lysosomal dysfunction in diabetic cardiomyopathy.

Diabetes is a major risk factor for a variety of cardiovascular complications, while diabetic cardiomyopathy, a disease specific to the myocardium independent of vascular lesions, is an important causative factor for increased risk of heart failure and mortality in diabetic populations. Lysosomes have long been recognized as intracellular trash bags and recycling facilities. However, recent studies have revealed that lysosomes are sophisticated signaling hubs that play remarkably diverse roles in adapting cell metabolism to an ever-changing environment. Despite advances in our understanding of the physiological roles of lysosomes, the events leading to lysosomal dysfunction and how they relate to the overall pathophysiology of the diabetic heart remain unclear and are under intense investigation. In this review, we summarize recent advances regarding lysosomal injury and its roles in diabetic cardiomyopathy.

Acute hyperglycemia compromises the responses of choroidal vessels using swept-source optical coherence tomography during dark and light adaptations.

Purpose: To clarify the effects of acute hyperglycemia on the responses of choroidal structural components and vascularity index during light modulation in healthy participants using techniques including image binarization and artificial intelligence (AI) segmentation based on swept-source optical coherence tomography (SS-OCT). Methods: Twenty-four eyes of 24 healthy participants were imaged at different stages after ambient light, 40 min of dark adaptation, and 5 min of light adaptation in two imaging sessions: control and after receiving 75 g of oral glucose solution. The choroidal structural parameters, including luminal volume (LV), stromal volume (SV), total choroidal volume (TCV), and choroidal vascularity index (CVI) within a 6 mm area were determined using a custom algorithm based on image binarization and AI segmentation of SS-OCT. These measurements were compared among the conditions after adjusting for axial length, age to identify the differences. Results: In the dark, CVI decreased (-0.36 ± 0.09%) significantly in acute hyperglycemia compared to the control condition. During the transition to ambient light, there was an increasing trend in the choroidal parameters compared with the control experiment. However, only TCV (0.38 ± 0.17 mm3) and LV (0.27 ± 0.10 mm3) showed a significant increase at the time point of 5 min after ambient light. Conclusion: Analysis of choroidal structural parameters and CVI based on SS-OCT images is a potentially powerful method to objectively reflect subtle changes in neurovascular coupling between the choroid and photoreceptor during dark adaptation.

A case series study of lacrimal canalicular laceration repair with the bi-canalicular stent.

Background: Lacrimal canalicular laceration can be caused by trauma on the ocular adnexa, such as penetrating or blunt injuries, accounting for approximately 16% of eyelid lacerations and 20% of eye traumas. Historically, canalicular anastomosis combined with bi-canalicular or mono-canalicular stent intubation has been used for canalicular laceration repair. In this study, we analyzed the epidemiological characteristics of lacrimal canalicular laceration and evaluate the clinical outcomes of repair using the bi-canalicular stent in central China. It aims to provide a reference for clinical work. Methods: This is a review of 338 patients (338 eyes) with eyelid lacrimal canaliculus laceration undergoing reparative bi-canalicular stent intubation from January 1st 2017 to December 30th 2020. The analyzed data included demographics, the place of occurrence of the trauma, the mechanism of injury, additional injury, and surgical outcomes at follow-up. The outcomes included anatomic success, functional success, and complications. Results: The average age was 39.6±20.0 years (1 to 88 years). Of all the 338 patients, 254 (75.15%) patients were men. Upper and lower canalicular lacerations were seen in 68 (20.12%) and 256 (75.74%) patients, respectively. Also, 14 patients (4.14%) presented with both upper and lower canalicular lacerations. Most injuries occurred on the streets (146, 43.20%), followed by the home in 111 (32.84%) patients. Traffic accidents were the leading cause of injury (127, 37.57%), including 72 (21.30%) cases of electric bike-associated accidents, followed by fall-related trauma in 65 (19.23%) cases. During the follow-up, there were 6 (1.78%) patients with eyelid ectropion and 9 (2.66%) patients with stent extrusion and loss due to eye rubbing and pulling the sutures out. At the end of follow-up, the anatomical success rate was 95.86% and the functional success rate was 89.64%. Conclusions: Electric bike-associated accidents occurring on the streets is the current leading cause of injury in central China. Lacrimal canalicular laceration repair with a bi-canalicular stent offers an effective surgical therapeutic strategy for traumatic canalicular lacerations. In addition, avoiding traffic accidents is also one way prevent lacrimal canalicular laceration.

Spectral broadening of a mixed Nd: CYGA crystal with tunable laser operation beyond 1100†nm.

A broader emission band of the novel Nd: CaY0.9Gd0.1AlO4 (Nd: CYGA) mixed crystal was proved by the introduction of Gd3+ ions in Nd: CaYAlO4 (Nd: CYA) crystal, and a diode-pump tunable Nd: CYGA laser operation was achieved successfully. Due to the broad emission spectrum with the full width at half maximum (FWHM) of 23 nm, a tuning range of 32 nm from 1075 nm to 1107 nm was achieved, and the results were considered to be the first time for Nd-doped crystals to be tuned to such a long wavelength at 1107 nm, which promotes the further development of near-infrared tunable lasers. The maximum output power was 1.05 W at the center wavelength of 1081.4 nm, corresponding to the slope efficiency of 26.6%. Furthermore, we also demonstrated a continuous-wave 1105 nm laser with the output power of 53 mW. Our work indicates that Nd: CYGA crystal is a potential Nd-doped gain medium for generating all-solid-state near-infrared lasers.

The Predominant Sources of Heavy Metals in Different Types of Fugitive Dust Determined by Principal Component Analysis (PCA) and Positive Matrix Factorization (PMF) Modeling in Southeast Hubei: A Typical Mining and Metallurgy Area in Central China.

To develop accurate air pollution control policies, it is necessary to determine the sources of different types of fugitive dust in mining and metallurgy areas. A method integrating principal component analysis and a positive matrix factorization model was used to identify the potential sources of heavy metals (HMs) in five different types of fugitive dust. The results showed accumulation of Mn, Fe, and Cu can be caused by natural geological processes, which contributed 38.55% of HMs. The Ni and Co can be released from multiple transport pathways and accumulated through local deposition, which contributed 29.27%. Mining-related activities contributed 20.11% of the HMs and showed a relatively high accumulation of As, Sn, Zn, and Cr, while traffic-related emissions contributed the rest of the HMs and were responsible for the enrichment in Pb and Cd. The co-applied source-identification models improved the precision of the identification of sources, which revealed that the local geological background and mining-related activities were mainly responsible for the accumulation of HMs in the area. The findings can help the government develop targeted control strategies for HM dispersion efficiency.

A comprehensive analysis of the components of common weed pollen and related allergens in patients with allergic diseases in southern China.

BACKGROUND: Pollen allergens are vital contributors to allergic diseases. The frequency and coreactivity pattern of allergens are closely related to geographical distribution. OBJECTIVE: In this study, we aimed to characterize the prevalence of the molecular components of the common weed pollen allergens, birch pollen, walnut, and cross-reactive carbohydrate determinant (CCD), as well as investigate the relationship between the allergens and CCD in Chinese pollen-sensitized patients with allergic diseases. METHODS: Based on previous vegetation surveys, serum samples from 165 pollen-sensitized patients with allergic diseases in Guangdong Province in southern China were used to test 19 crude allergen extracts, their components, and CCD using component-resolved diagnosis (CRD). Moreover, the potential associations among CCD, allergens, and their components were described. RESULTS: In the 165 samples, the most common sensitized allergens were goosefoot (43.0%), ragweed (40.6%), walnut (37.6%), walnut tree (37.6%), and mugwort (37.0%), followed by platane (35.2%), cocklebur (27.9%), and birch (24.2%). The positivity rate of CCD was 39.4%. Among the samples positive for mugwort, 11 (18.0%), 15 (24.6%), and 15 (24.6%) were positive for Art v 1, Art v 2, and Art v 3, respectively. Among the 67 patients sensitized to ragweed, only five (7.5%) were positive for Amb a 1. In the 40 patients sensitized to birch, Bet v 2 had the highest positivity rate (40.0%). There were 62 patients who were sensitized to walnut. Their components had a lower positivity rate (less than 15%). The hierarchical clustering and optimal scale analysis showed that Art v 4 and Bet v 2 were closely related, and 91.9% of CCD-positive samples were polysensitized. Meanwhile, Spearman's rank correlation method showed that CCD was closely correlated with the sensitization of crude allergen extracts, and there was a low correlation between CCD and allergen components. CCD was highly correlated with goosefoot, ragweed, and walnut trees (r＞0.8). Moreover, there was a strong relationship between the levels of Jug r 3 and Art v 3 (r = 0.78; P < 0.001). CONCLUSIONS: In southern China, the weed pollens (ragweed, cocklebur, and goosefoot) exhibited higher positivity rates in adults and had a stronger relationship with CCD but not with mugwort. The positivity rate of allergen components was not high. CCD-positive samples were always polysensitized.

Sulfonylurea receptor 1-expressing cancer cells induce cancer-associated fibroblasts to promote non-small cell lung cancer progression.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression; however, how CAFs are induced remains elusive. Sulfonylurea receptor 1 (SUR1) is a tumor-enhancer in non-small cell lung carcinoma (NSCLC). Here, we probed the influence of SUR1-expressing cancer cells on CAFs. Results showed that high SUR1 expression positively correlated with α-SMA positive staining of CAFs in tumor tissues and poor prognosis of NSCLC patients. SUR1 contributed to normal fibroblast (NF) transformation into CAFs and facilitated the growth and metastasis of NSCLC in vivo. Conditioned medium (CM) and exosomes from SUR1-expressing cancer cells induced CAFs and promoted fibroblast migration. In cancer cells, SUR1 promoted p70S6K-induced KH-type splicing regulatory protein (KHSRP) phosphorylation at S395 to inhibit the binding of KHSRP with let-7a precursor (pre-let-7a) and decreasing mature let-7a-5p expression in cancer cells and exosomes. Let-7a-5p delivered by exosomes blocked NF transformation into CAFs by targeting TGFBR1 to inactivate the TGF-ß signaling pathway. Glibenclamide, which targets SUR1, restrained CAFs and suppressed tumor growth in patient-derived xenograft models. Furthermore, we found that let-7a-5p was decreased in the tissues and plasma exosomes of NSCLC patients. In summary, SUR1-expressing cancer cells induce NF transformation into CAFs in the tumor microenvironment and promote NSCLC progression by transferring less exosomal let-7a-5p. Glibenclamide is a promising anti-cancer drug, and plasma exosomal let-7a-5p level is a potential diagnostic biomarker for NSCLC patients. These findings provide new therapeutic strategies by targeting SUR1 in NSCLC.

Longitudinal association between muscle strength and depression in middle-aged and older adults: A 7-year prospective cohort study in China.

BACKGROUND: Evidence regarding the associations between muscle strength in different parts of the body and depression is lacking. This study examined whether poor muscle strength is associated with a higher incidence of depression in a large cohort of middle-aged and older adults. METHODS: In total, 5,228 middle-aged and older adults from the China Health and Retirement Longitudinal Study without depression at baseline were followed for 7 years. Their demographic characteristics, chronic diseases and lifestyle behaviors were assessed. After adjusting for relevant variables, a Cox regression was used to determine the relationship between muscle strength and incident depression. RESULTS: Over 32,544 person-years of follow-up, 1,490 participants developed depression. Low muscle strength at baseline was associated with a higher 7-year incident of depression, even after excluding those who developed depression within 2 years. After adjusting for confounding factors, it was found that a higher baseline relative handgrip strength was a protective factor against depression (HR [95% CI]=0.575 [0.430-0.768] for the lowest quartile vs. the highest quartile; p<0.001). Longer times on the 5TSTS test were a risk factor for depression (HR [95% CI]=1.321 [1.077-1.621] for the lowest quartile vs. the highest quartile; p = 0.007). When the strengths of the upper and lower limbs were considered together, the hazard ratio for depression in people with relatively greater muscle strength was 0.463 (95% CI=0.307-0.699; p<0.001). CONCLUSIONS: Muscle strength could be predictive of depression, and the combined measurement of upper and lower limb muscle strength can improve the predictive ability.

The association between pulmonary function and depression in middle-aged and elderly people in China: The role of cognitive ability and sleep time.

BACKGROUND: Depression is a common mental disorder in middle-aged and elderly people, which seriously affects their physical health and life quality.So far, whether pulmonary function is a factor in depression has not been tested.The purpose of this study was to test whether pulmonary function was independently associated with depression and to assess the effects of cognitive ability and sleep time on this association. METHODS: In this analysis, 5,235 participants from the Chinese Longitudinal Study of Health and Retirement were included. Participants were registered in 2015 and followed up in 2018. The relationship between pulmonary function and depression was estimated by binary logistic regression model. The mediated role of cognitive ability was examined by intermediary analysis, and the interaction between pulmonary function and sleep time on depression was discussed. RESULTS: After adjusting for confounding factors, it was found that higher baseline pulmonary function was the protective factor of depression (OR [95%CI]=0.524 [0.394-0.697] for the lowest quantile vs the highest quantile). Cognitive ability explained 14.55% of the association between pulmonary function and depression, pulmonary function and sleep time on the effects of depression have a combined interaction, RERI (95%CI) = 0.545 (0.053-1.038). CONCLUSIONS: High baseline pulmonary function is independently associated with a lower risk of depression, which is partly mediated by cognitive ability. Pulmonary function and sleep time have synergy with the effects of depression. These findings show that pulmonary function, cognitive ability and sleep time are reliable predictors of depression.

The miR-345-3p/PPP2CA signaling axis promotes proliferation and invasion of breast cancer cells.

Breast cancer is the most common malignancy among women worldwide. Functional studies have demonstrated that miRNA dysregulation in many cases of cancer, in which miRNAs act as either oncogenes or tumor suppressor. Here we report that miR-345-3p is generally upregulated in breast cancer tissues and breast cancer cell lines. Overexpression and inhibition of miR-345-3p revealed its capacity in regulating proliferation and invasion of breast cancer cells. Further research identified protein phosphatase 2 catalytic subunit alpha (PPP2CA), a suppressor of AKT phosphorylation, as a candidate target of miR-345-3p. In vitro, miR-345-3p mimics promoted AKT phosphorylation by targeting its negative regulator, PPP2CA. Blocking miR-345-3p relieved its inhibition of PPP2CA, which attenuated PI3K-AKT signaling pathway. In vivo, inhibiting miR-345-3p by miR-345-3p-inhibition lentivirus suppressed tumor growth and invasiveness in mice. Together, the miR-345-3p/PPP2CA signaling axis exhibits tumor-promoting functions by regulating proliferation and invasion of breast cancer cells. These data provide a clue to novel therapeutic approaches for breast cancer.

Clinical Analysis of Adult Severe Open-Globe Injuries in Central China.

Purpose: To describe the characteristics, management, and outcomes of adult severe open-globe injured (OGI) eyes. Methods: Retrospective chart review of inpatients with initial visual acuity (VA) of light perception (LP) or no light perception (NLP) associated with OGI between 2017 and 2020 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital. Results: Six hundred twenty-five eyes of 622 adult patients with initial VA of LP or NLP associated with open-globe injuries (OGIs) were included. The mean age was 47.8 ± 14.1 years with the range from 18 to 91 years. Significant male predominance was noted (81.5%). The most common type of these severe OGIs was rupture (65.8%). Traffic accidents accounted for 13.5% followed by fall/tumble (10.9%) and nail/wire (10.9%) of all the severe OGIs. Almost half of the injuries happened at workplace (47.2%). Initially, 78.7% eyes just received primary debridement and wound closure, while 8.5% eyes with no possible of anatomical reconstruction received evisceration. After initial management, 350 eyes received subsequent operation, including 239 eyes underwent vitrectomy + silicone oil/(+cataract remove). Finally, over 6 months follow-up, 137 eyes (21.9%) were eviscerated, 150 eyes (24.0%) got atrophied, while 132 eyes (21.1%) retain some VA. Fifty-three eyes (8.5%) got VA of 0.3-1.5. Conclusion: Severe OGIs are most seen in the young, middle-aged, and male working population and remain a serious public health problem, resulting in significant vision loss or Evisceration of eyes. Effective preventive measures should be taken for the individuals in these groups.