IL-33 regulates adipogenesis via Wnt/ß-catenin/PPAR-γ signaling pathway in preadipocytes.

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic-related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/ß-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/ß-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.

A real-world clinicopathological model for predicting pathological complete response to neoadjuvant chemotherapy in breast cancer.

Purpose: This study aimed to develop and validate a clinicopathological model to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and identify key prognostic factors. Methods: This retrospective study analyzed data from 279 breast cancer patients who received NAC at Zhejiang Provincial People's Hospital from 2011 to 2021. Additionally, an external validation dataset, comprising 50 patients from Lanxi People's Hospital and Second Affiliated Hospital, Zhejiang University School of Medicine from 2022 to 2023 was utilized for model verification. A multivariate logistic regression model was established incorporating clinical, ultrasound features, circulating tumor cells (CTCs), and pathology variables at baseline and post-NAC. Model performance for predicting pCR was evaluated. Prognostic factors were identified using survival analysis. Results: In the 279 patients enrolled, a pathologic complete response (pCR) rate of 27.96% (78 out of 279) was achieved. The predictive model incorporated independent predictors such as stromal tumor-infiltrating lymphocyte (sTIL) levels, Ki-67 expression, molecular subtype, and ultrasound echo features. The model demonstrated strong predictive accuracy for pCR (C-statistics/AUC 0.874), especially in human epidermal growth factor receptor 2 (HER2)-enriched (C-statistics/AUC 0.878) and triple-negative (C-statistics/AUC 0.870) subtypes, and the model performed well in external validation data set (C-statistics/AUC 0.836). Incorporating circulating tumor cell (CTC) changes post-NAC and tumor size changes further improved predictive performance (C-statistics/AUC 0.945) in the CTC detection subgroup. Key prognostic factors included tumor size >5cm, lymph node metastasis, sTIL levels, estrogen receptor (ER) status and pCR. Despite varied pCR rates, overall prognosis after standard systemic therapy was consistent across molecular subtypes. Conclusion: The developed predictive model showcases robust performance in forecasting pCR in NAC-treated breast cancer patients, marking a step toward more personalized therapeutic strategies in breast cancer.

Risk factors and renal outcomes of AKI in children with secondary steroid-resistant nephrotic syndrome.

BACKGROUND: Acute kidney injury (AKI) is increasingly prevalent in children with nephrotic syndrome (NS). It is associated with adverse outcomes in NS, especially steroid-resistant nephrotic syndrome (SRNS). The incidence, risk factors and outcomes of AKI in secondary SRNS remain undefined. The main objectives of this study were to determine the risk factors and prognosis of AKI in hospitalized children with secondary SRNS. MATERIAL AND METHODS: This retrospective study was conducted from January 2014 to December 2019, involving 172 hospitalizations with secondary SRNS admitted to the First Affiliated Hospital of Sun Yat-sen University. AKI was defined and classified in accordance with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines. RESULTS: AKI was found in 67 (39.0%) of 172 hospitalizations with secondary SRNS. Average age of onset in our group is 4.4 (3.1, 6.7) years with AKI and 3.7 (1.8, 5.6) years without AKI. Urea nitrogen level is 5.9 (4.1, 10.0) mmol/L with AKI and 5.1 (3.7, 7.0) mmol/L. Uric acid level is 446.0 (340.0, 567.0) umol/L with AKI and 401.0 (303.0, 496.0) umol/L. 24-h urinary protein level is 4.14 (2.9, 6.5) g with AKI and 2.5 (1.3, 5.3) without AKI. Multivariate logistic regression revealed that infection (OR = 5.287; 95% confidence interval, 2.349 to 11.899; p < 0.001), age at onset (OR = 1.180; 95% confidence interval, 1.032 to 1.349; p = 0.015) and uric acid level (OR = 1.003; 95% confidence interval, 1.000 to 1.006; p = 0.031) were significantly associated with the development of AKI in children with secondary SRNS. Among 72 children with secondary SRNS, six went to end-stage kidney disease (ESKD). Children in the AKI group were more likely to progress to ESKD compared with children in the non-AKI group (p = 0.017) with a median follow-up of 48.5months. CONCLUSION: AKI occurred in 39.0% of total hospitalizations associated with secondary SRNS. Risk factors including infection, age of onset, and uric acid level are associated with AKI in children with secondary SRNS. Furthermore, AKI was identified as a risk factor for the progression of secondary SRNS to ESKD.

Association between co-infection with Chlamydia trachomatis or Mycoplasma genitalium and cervical lesions in HPV-positive population in Hunan, China: a cross-sectional study.

OBJECTIVES: The aim of this study was to determine the prevalence of Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) among HPV-positive women undergoing colposcopy at the Second Xiangya Hospital of Central South University, Hunan, China. Additionally, we aimed to assess the impact of C. trachomatis or M. genitalium co-infection with HPV on the severity of cervical lesions. METHODS: We collected HPV data, cervical cytology results, and demographic information from 439 women attending colposcopy. Cervical swabs were obtained for simultaneous amplification testing (SAT) of C. trachomatis and M. genitalium. Multivariate logistic regression analyses were performed to examine the association between sexually transmitted pathogens and cervical lesions. RESULTS: Among the participants, C. trachomatis was detected in 17 (3.87%) individuals, and M. genitalium in 16 (3.64%) individuals. There was no co-infection of C. trachomatis and M. genitalium. The highest prevalence of M. genitalium was observed in women aged 19-30 years (10.20%; 95% CI, 1.41-18.99%), with a subsequent decline in prevalence with increasing age (Ptrend = 0.014). The most common HPV subtype in our study was HPV52 (30.79%), followed by HPV16 (18.62%), HPV58 (16.95%), and HPV53 (10.02%). Infection with HPV16 (OR = 3.43, 95% CI, 2.13-5.53), HPV31 (OR = 3.70, 95% CI, 1.44-9.50), and HPV33 (OR = 3.71, 95% CI, 1.43-9.67) was associated with an increased severity of cervical lesions, while HPV53 infection was not likely to lead to advanced cervical lesions (OR = 0.45, 95% CI, 0.23-0.89). The leukocyte level in vaginal secretions (P = 0.042) and cervical cytology results (P < 0.001) showed associations with the degree of cervical lesions. However, there was no significant association between C. trachomatis or M. genitalium infection and the severity of cervical lesions, nor with their co-infection with HPV16. CONCLUSIONS: There was no correlation between co-infection of Chlamydia trachomatis or Mycoplasma genitalium and the degree of cervical lesions in HPV-positive population in Hunan, China. Our findings emphasized the need to pay more attention to M. genitalium infection among young women. Increased levels of leukocytes in vaginal secretions may be linked to cervical lesions. HPV16, HPV31, and HPV33 in Hunan province, China, may exhibit higher cervical pathogenicity.

Attachment style and attention bias to emotional information: The moderating effect of stress, stimulus characteristics, and attention stage.

OBJECTIVE: We examined whether insecurely attached individuals exhibit an attention bias to emotional information, and further tested the potential moderating role of stress, information valence, information attachment relevance, and attention stage. BACKGROUND: Attachment style can predict people's attention to emotional information. However, the empirical findings are inconsistent, making it difficult to determine the associations between attachment style and attention bias to emotional information. METHOD: We included 68 studies (N = 5417) across 46 published and unpublished articles (the initial pool was 627 articles) in the meta-analysis. RESULTS: People high on attachment avoidance exhibited decreased attention toward emotional stimuli (d = -0.129, p = 0.020), which was not affected by stress, information valence, information attachment relevance, or attention stage. Conversely, people high on attachment anxiety exhibited increased attention toward emotional stimuli, especially under stress, if the information was attachment-related, and during late-stage attentional processing. They exhibited an early bias away from and a late bias toward emotional information, which was intensified under stress. CONCLUSION: Our findings support the proposition that people high on attachment avoidance use deactivating strategies in attentional processing; whereas people high on attachment anxiety use hyperactivating strategies, especially when resources are limited (under stress). When resources are available, and it is relatively early in the process, people high on attachment anxiety respond similarly to those high on attachment avoidance.

miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFBR2

Objective Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor β receptor 2 (TGFβR). Methods We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial–mesenchymal transition (EMT) were assessed, while its effects on TGFβR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. Results Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFβR2. Conclusion The miRNA miR-17-5p can negatively regulate the expression of TGFβR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC (AU)

Boosting attachment security promotes prosociality: The mediating effect of moral disengagement.

While attachment security is known to promote prosocial behaviour, a closer examination is needed to clarify the active mechanism in this relationship. We addressed this issue by examining the mediation effect of moral disengagement in two studies. Participants were assigned to the control priming group or the attachment security priming group. After the priming procedure, they completed the measurements of a sense of security, moral disengagement and prosocial behaviour. The results from both studies showed that compared with control priming, attachment security priming enhanced prosociality. Furthermore, mediation analysis showed that moral disengagement mediated the relationship between attachment security and prosociality. The present findings extend the understanding of the underlying mechanisms of attachment security and prosociality, and provide insights into the effectiveness of boosting attachment security in intervening in moral disengagement.

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.

Incidence of relapse and frequently relapsing/steroid-dependent nephrotic syndrome in Chinese children with steroid-sensitive nephrotic syndrome: A cohort study.

AIM: This study aimed to investigate the incidence of relapse and FR/SDNS in Chinese children with SSNS and to develop clinical prediction models for relapse and FR/SDNS. METHODS: This retrospective cohort study involved 339 newly onset SSNS patients between 2006 and 2016. The incidence of relapse and FR/SDNS were estimated using the Kaplan-Meier method. Prediction models were constructed based on Cox proportional-hazards regression. RESULTS: The median follow-up time was 8.7 years. The cumulative incidence of relapse at 1-, 2-, and 5-year was 51.0%, 62.5%, and 66.6%. The cumulative incidence of FR/SDNS at 1-, 2-, and 5-year was 18.4%, 29.0%, and 32.9%. The final prediction model for first relapse included four variables (serum albumin, triglycerides, IgM, and time to first remission). The model's discriminative ability was low (Harrell's C index = 0.62). The final prediction model for FR/SDNS included four variables (serum albumin, lipoprotein(a), time to first remission, and time to first relapse). The discrimination and calibration of the prediction model for FR/SDNS were acceptable (Harrell's C index = 0.73, Brier score at 1- and 2-year were 0.11 and 0.17). CONCLUSION: The first relapse and FR/SDNS mainly occurred in the first 2 years after initial SSNS onset. The prediction model for relapse developed using common clinical parameters performed poorly, while the prediction model for FR/SDNS might be useful.

GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages.

Pyroptosis, a type of programmed necrosis associated with inflammatory, is a host defense mechanism against microbial infections. Although Chlamydia has been shown to induce pyroptosis, whether pyroptosis directly impacts the growth of Chlamydia has not been demonstrated. In this study, we found that C. trachomatis L2 infection of the mouse macrophage RAW 264.7 cells induced pyroptosis by monitoring the ultrastructural changes under transmission electron microscopy and the release of LDH and IL-1ß. More importantly, this C. trachomatis-triggered pyroptosis with activation of caspase-1 and caspase-11 was also accompanied by gasdermin D (GSDMD) activation. Suppression of these two inflammatory caspases inhibited GSDMD activation. Interestingly, the C. trachomatis-triggered pyroptosis significantly inhibited the intracellular growth of C. trachomatis since inactivation of either GSDMD or caspase-1/11 significantly rescued infectious C. trachomatis yields, which suggests pyroptosis response can be utilized as an intrinsic mechanism to restrict C. trachomatis intracellular infection in addition to the well- documented extrinsic mechanisms by recruiting and enhancing inflammatory responses. This study may reveal novel targets for attenuating C. trachomatis infectivity and/or pathogenicity.

miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFßR2.

OBJECTIVE: Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor ß receptor 2 (TGFßR). METHODS: We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial-mesenchymal transition (EMT) were assessed, while its effects on TGFßR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. RESULTS: Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFßR2. CONCLUSION: The miRNA miR-17-5p can negatively regulate the expression of TGFßR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC.

Monolayer Graphene Terahertz Detector Integrated with Artificial Microstructure.

Graphene, known for its high carrier mobility and broad spectral response range, has proven to be a promising material in photodetection applications. However, its high dark current has limited its application as a high-sensitivity photodetector at room temperature, particularly for the detection of low-energy photons. Our research proposes a new approach for overcoming this challenge by designing lattice antennas with an asymmetric structure for use in combination with high-quality monolayers of graphene. This configuration is capable of sensitive detection of low-energy photons. The results show that the graphene terahertz detector-based microstructure antenna has a responsivity of 29 V·W-1 at 0.12 THz, a fast response time of 7 µs, and a noise equivalent power of less than 8.5 pW/Hz1/2. These results provide a new strategy for the development of graphene array-based room-temperature terahertz photodetectors.

Mitochondrial micropeptide MOXI promotes fibrotic gene transcription by translocation to the nucleus and bridging N-acetyltransferase 14 with transcription factor c-Jun.

Progressive fibrosis is a hallmark of chronic kidney disease, but we lack effective treatments to halt this destructive process. Micropeptides (peptides of no more than 100 amino acids) encoded by small open reading frames represent a new class of eukaryotic regulators. Here, we describe that the micropeptide regulator of ß-oxidation (MOXI) regulates kidney fibrosis. MOXI expression was found to be up-regulated in human fibrotic kidney disease, and this correlated with the degree of fibrosis and loss of kidney function. MOXI was expressed in the cytoplasm and mitochondria of cultured tubular epithelial cells and translocated to the nucleus upon Transforming Growth Factor-ß1 stimulation. Deletion of Moxi protected mice against fibrosis and inflammation in the folic acid and unilateral ureteral obstruction models. As a potential molecular therapy, treatment with an antisense MOXI oligonucleotide effectively knocked-down MOXI expression and protected against kidney fibrosis in both models. Bimolecular fluorescence complementation identified the enzyme N-acetyltransferase 14 (Nat14) and transcription factor c-Jun as MOXI binding partners. The MOXI/Nat14/c-Jun complex enhances basal and Transforming Growth Factor-ß1 induced collagen I gene promoter activity. Phosphorylation at T49 is required for MOXI nuclear localization and for complex formation with Nat14 and c-Jun. Furthermore, mice with a MoxiT49A point mutation were protected in the models of kidney fibrosis. Thus, our studies demonstrate a key role for the micropeptide MOXI in kidney fibrosis and identify a new function of MOXI in forming a transcriptional complex with Nat14 and c-Jun.

Surveillance of the Antimicrobial Susceptibility and Molecular Characteristics of Neisseria gonorrhoeae Isolates Collected in Changsha, China from 2016 to 2021.

Antibiotic treatment is critical for individuals infected with gonorrhea and preventing disease transmission. This study aimed to analyze the antimicrobial susceptibility and molecular epidemiological characteristics of Neisseria gonorrhoeae isolates in Changsha, China. A total of 271 N.gonorrhoeae isolates collected from the clinical laboratories of two hospitals between 2016 and 2021 were analyzed for antimicrobial susceptibility using the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was conducted for genotyping, and phylogenetic analysis was performed using the porB and tbpB sequences. The results showed that antimicrobial resistance against ciprofloxacin, tetracycline, and penicillin was high, and these drugs are no longer recommended for the treatment of gonorrhea. All isolates were susceptible to spectinomycin. However, in 2016-2021, a total of 15 (5.5%) ceftriaxone (CRO)-resistant strains and 31 (11.4%) isolates with decreased susceptibility to CRO were found, and the resistance rate to azithromycin had reached 7.1% in 2016-2017. Epidemiologically, the mosaic penA allele was identified in all CRO-resistant isolates. Based on NG-MAST, ST5061 was the most prevalent ST. Phylogenetic analysis suggested that the resistant isolates did not cluster independently. Despite focus on the local situation, this study raises the need for better gonorrhea medication and highlights that CRO may not be adequate as first-line treatment for gonorrhea in Changsha.

Ultrasensitive Self-Driven Terahertz Photodetectors Based on Low-Energy Type-II Dirac Fermions and Related Van der Waals Heterojunctions.

The exotic electronic properties of topological semimetals (TSs) have opened new pathways for innovative photonic and optoelectronic devices, especially in the highly pursuit terahertz (THz) band. However, in most cases Dirac fermions lay far above or below the Fermi level, thus hindering their successful exploitation for the low-energy photonics. Here, low-energy type-II Dirac fermions in kitkaite (NiTeSe) for ultrasensitive THz detection through metal-topological semimetal-metal heterostructures are exploited. Furthermore, a heterostructure combining two Dirac materials, namely, graphene and NiTeSe, is implemented for a novel photodetector exhibiting a responsivity as high as 1.22 A W-1 , with a response time of 0.6 µs, a noise-equivalent power of 18 pW Hz-0.5 , with outstanding stability in the ambient conditions. This work brings to fruition of Dirac fermiology in THz technology, enabling self-powered, low-power, room-temperature, and ultrafast THz detection.

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course.

Immune checkpoint inhibitors (ICIs) are a revolutionary breakthrough in the field of cancer by modulating patient's own immune system to exert anti-tumor effects. The clinical application of ICIs is still in its infancy, and their dosing regimens need to be continuously adjusted. Pharmacokinetic/pharmacodynamic studies showed a significant plateau in the exposure-response curve, with high receptor occupancy and plasma concentrations achieved at low dose levels. Coupled with concerns about drug toxicity and heavy economic costs, there has been an ongoing quest to reevaluate the current ICI dosing regimens while preserving maximum clinical efficacy. Many clinical data showed remarkable anticancer effects with ICIs at the doses far below the approved regimens, indicating the possibility of dose reduction. Our review attempts to summarize the clinical evidence for ICIs regimens with lower-dose, less-frequency, shorter-course, and provide clues for further ICIs regimen optimization.

Dyslipidemia may be a risk factor for progression in children with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is often chronically progressive and commonly accompanied by dyslipidemia. However, the intrinsic relationship between dyslipidemia and IgAN remains to be elucidated. This study aimed to investigate the impact of different types of dyslipidemia on clinical and pathological characteristics in children with IgAN. METHODS: In our retrospective cohort study from January 2006 to January 2021, 276 children with IgAN were ultimately included in the baseline analysis, and 169 were included in the follow-up analysis. The clinical and pathological features of different types of dyslipidemia and their effect on kidney prognosis were analyzed. RESULTS: Children in the dyslipidemia group had more severe clinical characteristics (higher blood urea nitrogen, serum uric acid, and 24-h proteinuria; higher proportion of hypertension; and lower serum albumin and estimated glomerular filtration rate) and pathological changes (higher proportion of Lee grades IV-V and E1, S1, and C2 in MEST-C). Furthermore, the clinical and pathological characteristics were worse in the mixed hyperlipidemia group. Multivariate logistic analysis showed that hypertension, steroid treatment, lower serum albumin, severe proteinuria, and segmental glomerulosclerosis were independent risk factors for dyslipidemia in children with IgAN. The Kaplan-Meier analysis revealed that the probability of kidney survival in children with dyslipidemia was lower than that in those without dyslipidemia, with a median follow-up of 5.9 years. CONCLUSIONS: Children with IgAN and dyslipidemia, especially mixed hyperlipidemia, are prone to more severe clinical and pathological changes. Our study provides further insight into dyslipidemia as a potential risk factor in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hybrid Dirac semimetal-based photodetector with efficient low-energy photon harvesting.

Despite the considerable effort, fast and highly sensitive photodetection is not widely available at the low-photon-energy range (~meV) of the electromagnetic spectrum, owing to the challenging light funneling into small active areas with efficient conversion into an electrical signal. Here, we provide an alternative strategy by efficiently integrating and manipulating at the nanoscale the optoelectronic properties of topological Dirac semimetal PtSe2 and its van der Waals heterostructures. Explicitly, we realize strong plasmonic antenna coupling to semimetal states near the skin-depth regime (λ/104), featuring colossal photoresponse by in-plane symmetry breaking. The observed spontaneous and polarization-sensitive photocurrent are correlated to strong coupling with the nonequilibrium states in PtSe2 Dirac semimetal, yielding efficient light absorption in the photon range below 1.24 meV with responsivity exceeding ∼0.2 A/W and noise-equivalent power (NEP) less than ~38 pW/Hz0.5, as well as superb ambient stability. Present results pave the way to efficient engineering of a topological semimetal for high-speed and low-energy photon harvesting in areas such as biomedical imaging, remote sensing or security applications.

Exosomal miR-552-5p promotes tumorigenesis and disease progression via the PTEN/TOB1 axis in gastric cancer.

Purpose Gastric cancer (GC) is associated with rapid disease progression and poor patient prognosis, highlighting the pressing need for new biomarkers to facilitate disease management. Exosomes are released by all cells and are ubiquitous in body fluids, thus giving them great potential as diagnostic biomarkers and therapeutic targets. MicroRNAs (miRNAs) can be transported by exosomes, and are a common target for regulation in cancer. Methods Our screen of miRNAs in the Gene Expression Omnibus and The Cancer Genome Atlas databases identified miR-552-5p as the most overexpressed miRNA in GC, and we investigated its function and mechanism of action. Results We detected high expression of miR-552-5p in GC tissues, plasma samples and cell lines. We found that miR-552-5p binds directly to the 3'-untranslated region of PTEN, and the resulting downregulation of PTEN in turn downregulates the tumor suppressor TOB1. Furthermore, experiments in cell culture and mice showed that miR-552-5p in exosomes is internalized by recipient cells, where it enhances proliferation, migration and the epithelial-mesenchymal transition, while suppressing the caspase-3 apoptotic pathway. These effects were reversed by inhibiting miR-552-5p. Conclusion GC-derived exosomal miR-552-5p facilitates tumorigenesis by interfering with the PTEN/TOB1 axis, providing new potential therapeutic targets.