A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning.

Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.

Transcriptomic and metabolomic analyses reveal that lemon extract prolongs Drosophila lifespan by affecting metabolism.

Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.

Multiple Treatment of Triple-Negative Breast Cancer Through Gambogic Acid-Loaded Mesoporous Polydopamine.

Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.

Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

The Causal Relationship between Plasma Myeloperoxidase Levels and Respiratory Tract Infections: A Bidirectional Mendelian Randomization Study.

Background: Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Materials and Methods: Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results: We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions: Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

Extreme Reconfiguration of Plastid Genomes in Papaveraceae: Rearrangements, Gene Loss, Pseudogenization, IR Expansion, and Repeats.

The plastid genomes (plastomes) of angiosperms are typically highly conserved, with extreme reconfiguration being uncommon, although reports of such events have emerged in some lineages. In this study, we conducted a comprehensive comparison of the complete plastomes from twenty-two species, covering seventeen genera from three subfamilies (Fumarioideae, Hypecooideae, and Papaveroideae) of Papaveraceae. Our results revealed a high level of variability in the plastid genome size of Papaveraceae, ranging from 151,864 bp to 219,144 bp in length, which might be triggered by the expansion of the IR region and a large number of repeat sequences. Moreover, we detected numerous large-scale rearrangements, primarily occurring in the plastomes of Fumarioideae and Hypecooideae. Frequent gene loss or pseudogenization were also observed for ndhs, accD, clpP, infA, rpl2, rpl20, rpl32, rps16, and several tRNA genes, particularly in Fumarioideae and Hypecooideae, which might be associated with the structural variation in their plastomes. Furthermore, we found that the plastomes of Fumarioideae exhibited a higher GC content and more repeat sequences than those of Papaveroideae. Our results showed that Papaveroideae generally displayed a relatively conserved plastome, with the exception of Eomecon chionantha, while Fumarioideae and Hypecooideae typically harbored highly reconfigurable plastomes, showing high variability in the genome size, gene content, and gene order. This study provides insights into the plastome evolution of Papaveraceae and may contribute to the development of effective molecular markers.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

[Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months]. / æ—©äº§å°äºŽèƒŽé¾„å„¿æ ¡æ­£0~24æœˆé¾„è¿½èµ¶ç”Ÿé•¿çš„çºµå‘ç ”ç©¶.

OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

In Situ Tumor Vaccine for Lymph Nodes Delivery and Cancer Therapy Based on Small Size Nanoadjuvant.

Tumor vaccine is a promising cancer treatment modality, however, the convenient antigens loading in vivo and efficient delivery of vaccines to lymph nodes (LNs) still remain a formidable challenge. Herein, an in situ nanovaccine strategy targeting LNs to induce powerful antitumor immune responses by converting the primary tumor into whole-cell antigens and then delivering these antigens and nanoadjuvants simultaneously to LNs is proposed. The in situ nanovaccine is based on a hydrogel system, which loaded with doxorubicin (DOX) and nanoadjuvant CpG-P-ss-M. The gel system exhibits ROS-responsive release of DOX and CpG-P-ss-M, generating abundant in situ storage of whole-cell tumor antigens. CpG-P-ss-M adsorbs tumor antigens through the positive surface charge and achieves charge reversal, forming small-sized and negatively charged tumor vaccines in situ, which are then primed to LNs. Eventually, the tumor vaccine promotes antigens uptake by dendritic cells (DCs), maturation of DCs, and proliferation of T cells. Moreover, the vaccine combined with anti-CTLA4 antibody and losartan inhibits tumor growth by 50%, significantly increasing the percentage of splenic cytotoxic T cells (CTLs), and generating tumor-specific immune responses. Overall, the treatment effectively inhibits primary tumor growth and induces tumor-specific immune response. This study provides a scalable strategy for in situ tumor vaccination.

Mucinous tubular and spindle cell carcinoma of the kidney: a report of seven cases.

OBJECTIVE: To further analyse the imaging features and tumour outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. MATERIALS AND METHODS: The current study retrospectively reviewed the clinical information of seven patients diagnosed with MTSCC at our institution from January 2011 to March 2023. RESULTS: The median age at diagnosis was 52 years (range, 32-66 years) and the majority of patients were female (71.4%). On conventional abdominal ultrasound, the majority of the tumours (5/7) were heterogeneous hypoechoic or slightly hypoechoic. Colour Doppler flow imaging showed blood flow within the tumour in 2 cases and peripheral blood flow signal in 1 case. On non-enhanced CT, all tumours had a spherical or ovoid shape, with an expansile growth mode, and had clear or unclear boundaries with the surrounding renal parenchyma. The tumours were either partially exophytic (n = 4) or parenchymal (n = 3), while no cases of completely exophytic tumour was observed (n = 0). On contrast-enhanced CT, the majority of tumours (5/7) showed a heterogenous pattern of enhancement and the mean tumour diameter was 6.7 ± 4.4 cm (range, 2.1-16.8 cm). All patients underwent partial or radical nephrectomy for pT1a (42.9%), pT1b (28.5%), pT2 (14.3%) or pT3b (14.3%) stage. Among these, 1 patient (14.3%) had a level I tumour thrombus at diagnosis and died of disease 24.5 months later. The remaining patients had no recurrence or metastasis. CONCLUSION: MTSCC is not universally indolent, which tends to occur in female patients of a broad range of ages. MTSCC is a hypovascular renal tumour, which is different from clear cell renal cell carcinoma (RCC); however, it is difficult to distinguish MTSCC from other hypovascular RCC subtypes because of the overlap of their imaging characteristics.

Influencing factors analysis of adaptability of cancer patients to return-to-work.

OBJECTIVES: To clarify the adaptability of cancer patients to return to work and explore its influencing factors. DESIGN: A cross-sectional study. SETTINGS/PARTICIPANTS: From March to October 2021, 283 cancer patients in the follow-up period were recruited from the oncology departments of four secondary and above hospitals and cancer friendship associations in Nantong city using self-developed scale of adaptability to return to work for cancer patients by convenience sampling method. METHODS: The contents included general sociodemographic data, disease-related data, cancer patients' readability to work Scale, Medical Coping Style Questionnaire, Social Support Rating Scale, Family Closeness and Readability Scale, General self-efficacy Scale and Social impact Scale. Paper questionnaires were used for face-to-face data collection, and SPSS17.0 was used for statistical analysis. Univariable analyses and multiple linear regression analysis were conducted. RESULTS: The overall score of cancer patients' adaptability to return to work was (87.05±20.255), (22.54±4.234) for the dimension of focused rehabilitation, (32.02±9.013) for the dimension of reconstruction effectiveness, and (32.49±9.023) for the dimension of adjustment planning. Multiple linear regression analysis showed that the current return to full-time work (ß =0.226, P 0.05), the current return to non-full-time work (ß =0.184, P 0.05), yield response (ß = -0.132, P 0.05), and general self-efficacy (ß =0.226, P 0.05) could affect their return to work adaptation. CONCLUSION: The results of status quo and influencing factors showed that the adaptability of cancer patients to return to work was generally higher in this study. Cancer patients who had participated in work, had lower yield coping scores and stigma scores, and higher self-efficacy scores and family adjustment and intimacy scores had better adaptability to return to work again. ETHICAL APPROVAL: It has been approved by the Human Research Ethics Committee of the Affiliated Hospital of Nantong University (Project No.202065).

The mechanisms related to fibroblasts in burn surface.

PURPOSE: Mesenchymal stem cells (MSCs) can promote burn wound healing, skin appearance, and function recovery by promoting the differentiation and migration of fibroblasts of a wound. The burn environment can activate the autophagy of MSCs. However, it is not clear whether this autophagy can affect the proliferation and migration of fibroblasts. METHODS: In this study, pretreated MSCs with rapamycin and 3-methyladenine modulated autophagy and co-cultured with fibroblasts of burn. Cell migration was detected by immunofluorescence chemical staining. Western blot analysis and enzyme-linked immunosorbent assay were performed to detect 2,3-Dioxygenase (IDO), cytokine synthesis inhibitory factor 10 (IL-10), cytokine synthesis inhibitory factor 6 (IL-6), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-ß1) proteins levels, and the autophagy proteins p62 and microtubule-associated protein LC3-II/I. RESULTS: We demonstrated that autophagy regulates MSCs survival and proliferation in burn wound transplants and found that autophagy inhibition with 3-methyladenine reduced MSCs-mediated, fibroblast proliferation and migration in burn environment. However, rapamycin-induced autophagy had the opposite effect and increased the TGF-ß1 expression. Therefore, we speculate that MSCs may promote fibroblast proliferation and migration by secreting TGF-ß1 via the AKT/mTOR (RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin) pathway. CONCLUSION: Autophagy of MSCs regulates burn wound fibroblast proliferation and migration by affecting TGF-ß1 and prostaglandin E2 production adjacent to MSCs transplanted on the burn wound. The results of this study provide a potential strategy for promoting MSCs treatment of burns.

Mental Distress and Professional Commitment among Chinese Medical Postgraduate Students: A Moderated Mediation of Psychological Capital and the Supervisor-Postgraduate Relationship.

This study determined the relationship between mental distress and professional commitment among medical postgraduate students, and the roles of psychological capital as a mediator and the supervisor-postgraduate relationship as a moderator. This cross-sectional study recruited 836 medical postgraduate students from eight medical universities and the medical college of comprehensive universities in Guangdong Province, China. Participants were assessed through questionnaires, which covered demographic items, the supervisor-postgraduate relationship scale, the psychological capital questionnaire, the symptom checklist - 90 (SCL -90), and the professional commitment scale. We used descriptive statistics to describe demographics and mental distress and professional commitment scores. Pearson's analysis was used to identify correlations between the variables and the SPSS PROCESS macro was performed to confirm mediating and moderating effects of psychological capital and the supervisor-postgraduate relationship. Mental distress was negatively related with professional commitment (r = -0.262, p < 0.01) and psychological capital (r = -0.442, p < 0.01). Psychological capital was positively associated with professional commitment (r = 0.486, p < 0.01). The confidence interval (CI) suggested that psychological capital mediated the relationship between mental distress and professional commitment (95% CI, -0.198 to - 0.143), and the supervisor-postgraduate relationship had a moderate role between psychological capital and professional commitment (95% CI, 0.069 to -0.212). Hence, educators may refer to these findings to improve professional commitment level among medical postgraduate students.

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis.

tRNA-derived small RNAs (tsRNAs) are derived from tRNA and include tRNA halves (tiRNAs) and tRNA fragments (tRFs). tsRNAs have been implicated in a variety of important biological functions, such as cell growth, transcriptional regulation, and apoptosis. Emerging evidence has shown that Ago1-guided and Ago2-guided tsRNAs are expressed at 3 and 30 days in Drosophila and that tRF biogenesis in fruit flies affects tRNA processing and tRNA methylation. However, a wide analysis of tsRNA patterns in different ages of Drosophila have not been reported via the small RNA sequencing method. In the present study, tsRNAs of young (7 days) and old (42 days) Drosophila were sequenced and their expression characteristics were analysed. Then, a specific tRF (named tRF-Trp-CCA-014) was determined and was found to be conserved in fruit flies, mice, and humans. The expression patterns of tRF-Trp-CCA-014 in different tissues and stages of fruit flies and mice, and mouse NIH/3T3 cells were detected. Furthermore, mouse embryonic fibroblast NIH/3T3 cells were used as a model to analyse the function and targets of tRF-Trp-CCA-014. The RNA-seq data of six groups (Mimics, Mimic NC, Inhibitors, Inhibitor NC, Aging (adriamycin), and Control (Normal)) in mouse NIH3T3 cells were analysed. The results showed that the number of tsRNAs at 42 days (417) was more than at 7 days (288); thus, it was enriched with age. tRFs-1 were the most enriched, followed by 5'-tRFs and 3'-tRFs. Twenty-one differentially expressed tsRNAs were identified between 7 days and 42 days. Then, the conserved tRF tRF-Trp-CCA-014 was identified and found to accumulate in aged fruit flies and aged mouse NIH3T3 cells. RNA-seq data showed that most differentially expressed genes were involved in the immune system, cancer: overview, and signal translation. Furthermore, tRF-Trp-CCA-014 was found to bind to the 3'UTR of H3C4 in a dual-luciferase reporter gene assay. tRF-Trp-CCA-014 and H3C4 were detected in the cytoplasm of aged NIH3T3 cells by RNA in situ hybridization. These results suggest that the H3C4 gene is the target of tRF-Trp-CCA-014. This study will advance the current understanding of tRF roles and their implication in Drosophila and mouse studies.

Cancer patients' return-to-work adaptation experience and coping resources: a grounded theory study.

OBJECTIVE: To explore the return-to-work adaptation experience and coping resources used by cancer patients. METHODS: With the help of the Nantong Cancer Friends Association, from June 2019 to January 2020, this study recruited 30 cancer patients who had returned to work using purpose sampling, snowball sampling and theoretical sampling. The researchers analyzed the data using initial-, focusing-, and theoretical coding. RESULTS: The adaptation of cancer patients to return-to-work is a rebuilding process by taking advantage of the available personal and external coping resources. The adaptation experience includes: focusing on rehabilitation, rebuilding self-efficacy, and adjusting plans. CONCLUSION: Medical staff should help patients mobilize coping resources to adapt to return to work.

Cadmium interference with iron sensing reveals transcriptional programs sensitive and insensitive to reactive oxygen species.

Iron (Fe) is an essential micronutrient whose uptake is tightly regulated to prevent either deficiency or toxicity. Cadmium (Cd) is a non-essential element that induces both Fe deficiency and toxicity; however, the mechanisms behind these Fe/Cd-induced responses are still elusive. Here we explored Cd- and Fe-associated responses in wild-type Arabidopsis and in a mutant that overaccumulates Fe (opt3-2). Gene expression profiling revealed a large overlap between transcripts induced by Fe deficiency and Cd exposure. Interestingly, the use of opt3-2 allowed us to identify additional gene clusters originally induced by Cd in the wild type but repressed in the opt3-2 background. Based on the high levels of H2O2 found in opt3-2, we propose a model where reactive oxygen species prevent the induction of genes that are induced in the wild type by either Fe deficiency or Cd. Interestingly, a defined cluster of Fe-responsive genes was found to be insensitive to this negative feedback, suggesting that their induction by Cd is more likely to be the result of an impaired Fe sensing. Overall, our data suggest that Fe deficiency responses are governed by multiple inputs and that a hierarchical regulation of Fe homeostasis prevents the induction of specific networks when Fe and H2O2 levels are elevated.

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus.

Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microglia-related inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment.

Global burden of gallbladder and biliary diseases: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND AND AIM: Gallbladder and biliary diseases (GBDs) are one of the most prevalent medical issues in the digestive system. This study was designed to describe the characteristics of prevalence, death, and disability-adjusted life years (DALYs) of GBDs during 1990-2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. METHODS: Prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. Countries and territories were categorized according to socio-demographic index (SDI) quintiles. RESULTS: The prevalence cases (127 345 732 to 193 493 378), death cases (82 430 to 124 941), and DALYs (4 604 821 to 6 352 738) of GBDs increased from 1990 to 2019. However, the age-standardized rates of indicators decreased over the 30-year period (prevalence, 2851.84 to 2350.78 per 100 000 population; death, 2.40 to 1.65 per 100 000 population; DALYs, 106.76 to 78.25 per 100 000 population). In 2019, the high and middle-high SDI regions had higher age-standardized prevalence rates, the low SDI region had the highest age-standardized death rate, and the middle SDI region had the highest DALYs and age-standardized DALYs rate of GBDs. Being female, older age, and high body mass index were important risk factors for the burden of GBDs. CONCLUSIONS: Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of GBDs should be promoted in middle, middle-high, and high SDI regions, while more medical resources should be provided to improve treatment levels in low SDI region.

A case of membranous nephropathy with Kimura's disease.

BACKGROUND: The association between membranous nephropathy (MN) and Kimura's disease (KD) has been reported in recent years. The treatment, effect, and prognosis of KD are still unclear. CASE REPORT: A 47-year-old KD patient developed a left axillary mass for 3 years and received surgical resection because of the lager mass in August 2016. Then he developed nephrotic syndrome 3 months later. Laboratory index revealed increased eosinophil count, decreased albumin and heavy proteinuria. Lymph node biopsy suggested KD, and renal biopsy suggested MN. He relapsed after a treatment with methylprednisolone (52 mg/d) alone and then tacrolimus (1.5 mg/12h) was added. The patient had no symptoms of relapse in the next 2 years. CONCLUSION: The combination therapy of surgery, methylprednisolone, and immunosuppressive agents may be effective in KD with MN.