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Abstract Objective To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). Methods Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. Results Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p

Abstract Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A ‘reader’ YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15’s actions in CRC cells.

Duodenal stump fistula (DSF) is a serious complication of radical gastrectomy for gastric cancer. Herein, we illustrated an innovative choice for treating duodenal stump fistulas by placing a modified sump drainage through trocar puncture into the DSF-related abscess (DSF-abscess) cavity. We retrospectively analyzed 974 consecutive patients who underwent gastrectomy for gastric cancer between 2011 and 2021. Of these patients, 34 who developed postoperative duodenal stump fistulas postoperatively were enrolled into our study, and their clinical data were retrospectively assessed. From January 2011 to December 2017, 15 patients received conventional treatments (percutaneous catheter drainage, PCD group) known as the traditional percutaneous method, and 19 patients from January 2018 to December 2021 received new treatments (Troca's SD group) consisting of conventional therapies and placement of a modified sump drainage through trocar puncture into DSF-abscess cavity. The demographics, clinical characteristics and treatment outcomes were compared between two groups. Compared with the PCD group, the rates of postoperative complications, duodenostomy creation, subsequent surgery, fistula healing rates of the DSF, and length of postoperative hospital stay were significantly decreased in the Troca SD group. However, there was no significant difference in the abscess recurrence rate and mortality rates. Trocar puncture with a modified sump drainage is an safe, effective, and technically feasible treatment for duodenal stump fistula after radical gastrectomy for gastric cancer. This novel technique should be further investigated using large-scale RCT research.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- and anti-angiogenic molecules, which plays a crucial role in tumor growth, invasion, and metastasis. With the advances in molecular and cellular biology, various biomolecules such as growth factors, chemokines, and adhesion factors involved in tumor angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules has driven anti-angiogenic treatment to become a promising strategy in anti-tumor therapy. The most widely used anti-angiogenic agents include monoclonal antibodies and tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) pathway. However, the clinical benefit of this modality has still been limited due to several defects such as adverse events, acquired drug resistance, tumor recurrence, and lack of validated biomarkers, which impel further research on mechanisms of tumor angiogenesis, the development of multiple drugs and the combination therapy to figure out how to improve the therapeutic efficacy. Here, we broadly summarize various signaling pathways in tumor angiogenesis and discuss the development and current challenges of anti-angiogenic therapy. We also propose several new promising approaches to improve anti-angiogenic efficacy and provide a perspective for the development and research of anti-angiogenic therapy.

BackgroundTo investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM).MethodsForty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs.ResultsCompared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%).ConclusionPatients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO.

Abstract An unprecedented warm sea surface temperature (SST) anomaly event, namely, the Blob, occurred in the northeast Pacific during the winter (October–January) of 2013/2014, causing substantial economic and ecological impacts. Here, we explore the driving forces of the Blob from both atmospheric and oceanic perspectives and show that the Blob primarily resulted from weak wintertime cooling due to the reduced air-sea heat flux transfer from the ocean to the atmosphere and the reduced horizontal advection of cold water in the upper ocean. Both mechanisms were attributed to an anomalous high-pressure system over the study region. Specifically, the anomalous air-sea heat flux, which was dominated by turbulent heat flux anomalies, was mainly induced by the increased air temperature (i.e., with a contribution of approximately 70%) and the weakened wind speed associated with the high-pressure system. The reduced horizontal heat advection was mainly due to the weakened winds acting on the ocean temperature meridional gradient. Using a regional ocean numerical model with different experimental runs, we evaluated the contributions of air temperature and wind drivers to the Blob at both the surface and subsurface of the ocean. The Blob was absent when the model was forced by climatology-air-temperature. Both the SST and integrated ocean heat content (OHC, 0–150 m) decreased, and the mixed layer depth (MLD) was deeper than that in the control run forced by real atmospheric conditions. In the climatology-winds experiment, obvious warm anomalies still existed, which were similar to but weaker than the control run. The SST (OHC) and MLD values in the climatology-winds run were between those of the climatology-air-temperature run and the control run. Compared to former studies that attribute the formation of the Blob to an anomalous air-sea heat flux and horizontal advection mainly induced by reduced winds, our study demonstrates that anomalous warm air temperatures played a more important role in its formation.

Citrus is mainly cultivated in acid soil with low boron (B) and high copper (Cu). In this study, Citrus sinensis seedlings were submitted to 0.5 (control) or 350 μM Cu (Cu excess or Cu exposure) and 2.5, 10, or 25 μM B for 24 weeks. Thereafter, H2O2 production rate (HPR), superoxide production rate (SAPR), malondialdehyde, methylglyoxal, and reactive oxygen species (ROS) and methylglyoxal detoxification systems were measured in leaves and roots in order to test the hypothesis that B addition mitigated Cu excess-induced oxidative damage in leaves and roots by reducing the Cu excess-induced formation and accumulation of ROS and MG and by counteracting the impairments of Cu excess on ROS and methylglyoxal detoxification systems. Cu and B treatments displayed an interactive influence on ROS and methylglyoxal formation and their detoxification systems. Cu excess increased the HPR, SAPR, methylglyoxal level, and malondialdehyde level by 10.9% (54.3%), 38.9% (31.4%), 50.3% (24.9%), and 312.4% (585.4%), respectively, in leaves (roots) of 2.5 μM B-treated seedlings, while it only increased the malondialdehyde level by 48.5% (97.8%) in leaves (roots) of 25 μM B-treated seedlings. Additionally, B addition counteracted the impairments of Cu excess on antioxidant enzymes, ascorbate-glutathione cycle, sulfur metabolism-related enzymes, sulfur-containing compounds, and methylglyoxal detoxification system, thereby protecting the leaves and roots of Cu-exposed seedlings against oxidative damage via the coordinated actions of ROS and methylglyoxal removal systems. Our findings corroborated the hypothesis that B addition alleviated Cu excess-induced oxidative damage in leaves and roots by decreasing the Cu excess-induced formation and accumulation of ROS and MG and by lessening the impairments of Cu excess on their detoxification systems. Further analysis indicated that the pathways involved in the B-induced amelioration of oxidative stress caused by Cu excess differed between leaves and roots.

BackgroundThe association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.MethodsFecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins.ResultsNon-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae, and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases.ConclusionWe revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.

Abstract Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

Litsea, a non-monophyletic group of the tribe Laureae (Lauraceae), plays important roles in the tropical and subtropical forests of Asia, Australia, Central and North America, and the islands of the Pacific. However, intergeneric relationships between Litsea and Laurus, Lindera, Parasassafras and Sinosassafras of the tribe Laureae remain unresolved. In this study, we present phylogenetic analyses of seven newly sequenced Litsea plastomes, together with 47 Laureae plastomes obtained from public databases, representing six genera of the Laureae. Our results highlight two highly supported monophyletic groups of Litsea taxa. One is composed of 16 Litsea taxa and two Lindera taxa. The 18 plastomes of these taxa were further compared for their gene structure, codon usage, contraction and expansion of inverted repeats, sequence repeats, divergence hotspots, and gene evolution. The complete plastome size of newly sequenced taxa varied between 152,377 bp (Litsea auriculata) and 154,117 bp (Litsea pierrei). Seven of the 16 Litsea plastomes have a pair of insertions in the IRa (trnL-trnH) and IRb (ycf2) regions. The 18 plastomes of Litsea and Lindera taxa exhibit similar gene features, codon usage, oligonucleotide repeats, and inverted repeat dynamics. The codons with the highest frequency among these taxa favored A/T endings and each of these plastomes had nine divergence hotspots, which are located in the same regions. We also identified six protein coding genes (accD, ndhJ, rbcL, rpoC2, ycf1 and ycf2) under positive selection in Litsea; these genes may play important roles in adaptation of Litsea species to various environments.

Abstract Background In China, nitrogen (N)-deficiency often occurs in Citrus orchards, which is one of the main causes of yield loss and fruit quality decline. Little information is known about the adaptive responses of Citrus carbon (C) and N metabolisms to N-deficiency. Seedlings of ‘Xuegan’ (Citrus sinensis (L.) Osbeck) were supplied with nutrient solution at an N concentration of 0 (N-deficiency), 5, 10, 15 or 20 mM for 10 weeks. Thereafter, we examined the effects of N supply on the levels of C and N in roots, stems and leaves, and the levels of organic acids, nonstructural carbohydrates, NH4 +-N, NO3 −-N, total soluble proteins, free amino acids (FAAs) and derivatives (FAADs), and the activities of key enzymes related to N assimilation and organic acid metabolism in roots and leaves. Results N-deficiency elevated sucrose export from leaves to roots, C and N distributions in roots and C/N ratio in roots, stems and leaves, thus enhancing root dry weight/shoot dry weight ratio and N use efficiency. N-deficient leaves displayed decreased accumulation of starch and total nonstructural carbohydrates (TNC) and increased sucrose/starch ratio as well as a partitioning trend of assimilated C toward to sucrose, but N-deficient roots displayed elevated accumulation of starch and TNC and reduced sucrose/starch ratio as well as a partitioning trend of assimilated C toward to starch. N-deficiency reduced the concentrations of most FAADs and the ratios of total FAADs (TFAADs)/N in leaves and roots. N-deficiency reduced the demand for C skeleton precursors for amino acid biosynthesis, thus lowering TFAADs/C ratio in leaves and roots. N-deficiency increased (decreased) the relative amounts of C-rich (N-rich) FAADs, thus increasing the molar ratio of C/N in TFAADs in leaves and roots. Conclusions Our findings corroborated our hypothesis that C and N metabolisms displayed adaptive responses to N-deficiency in C. sinensis seedlings, and that some differences existed between roots and leaves in N-deficiency-induced alterations of and C and N metabolisms.

Poor control of metabolic diseases induces kidney injury, resulting in microalbuminuria, renal insufficiency and, ultimately, chronic kidney disease. The potential pathogenetic mechanisms of renal injury caused by metabolic diseases remain unclear. Tubular cells and podocytes of the kidney show high expression of histone deacetylases known as sirtuins (SIRT1–7). Available evidence has shown that SIRTs participate in pathogenic processes of renal disorders caused by metabolic diseases. The present review addresses the regulatory roles of SIRTs and their implications for the initiation and development of kidney damage due to metabolic diseases. SIRTs are commonly dysregulated in renal disorders induced by metabolic diseases such as hypertensive nephropathy and diabetic nephropathy. This dysregulation is associated with disease progression. Previous literature has also suggested that abnormal expression of SIRTs affects cellular biology, such as oxidative stress, metabolism, inflammation, and apoptosis of renal cells, resulting in the promotion of invasive diseases. This literature reviews the research progress made in understanding the roles of dysregulated SIRTs in the pathogenesis of metabolic disease-related kidney disorders and describes the potential of SIRTs serve as biomarkers for early screening and diagnosis of these diseases and as therapeutic targets for their treatment.

Sarcomas, comprising approximately 1% of human malignancies, show a poor response to treatment and easy recurrence. Metabolic reprogramming play an important role in tumor development in sarcomas. Accumulating evidence shows that non-coding RNAs (ncRNAs) participate in regulating the cellular metabolism of sarcomas, which improves the understanding of the development of therapy-resistant tumors. This review addresses the regulatory roles of metabolism-related ncRNAs and their implications for sarcoma initiation and progression. Dysregulation of metabolism-related ncRNAs is common in sarcomas and is associated with poor survival. Emerging studies show that abnormal expression of metabolism-related ncRNAs affects cellular metabolism, including glucose, lipid, and mitochondrial metabolism, and leads to the development of aggressive sarcomas. This review summarizes recent advances in the roles of dysregulated metabolism-related ncRNAs in sarcoma development and stemness and describes their potential to serve as biological biomarkers for disease diagnosis and prognosis prediction, as well as therapeutic targets for treating refractory sarcomas.

Background: Sarcomas comprise approximately 1% of all human malignancies; treatment resistance is one of the major reasons for the poor prognosis of sarcomas. Accumulating evidence suggests that non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs, and circular RNAs, are important molecules involved in the crosstalk between resistance to chemotherapy, targeted therapy, and radiotherapy via various pathways. Methods: We searched the PubMed (MEDLINE) database for articles regarding sarcoma-associated ncRNAs from inception to August 17, 2022. Studies investigating the roles of host-derived miRNAs, long ncRNAs, and circular RNAs in sarcoma were included. Data relating to the roles of ncRNAs in therapeutic regulation and their applicability as biomarkers for predicting the therapeutic response of sarcomas were extracted. Two independent researchers assessed the quality of the studies using the Würzburg Methodological Quality Score (W-MeQS). Results: Observational studies revealed the ectopic expression of ncRNAs in sarcoma patients who had different responses to antitumor treatments. Experimental studies have confirmed crosstalk between cellular pathways pertinent to chemotherapy, targeted therapy, and radiotherapy resistance. Of the included studies, W-MeQS scores ranged from 3 to 10 (average score = 5.42). Of the 12 articles that investigated ncRNAs as biomarkers, none included a validation cohort. Selective reporting of the sensitivity, specificity, and receiver operating curves was common. Conclusions: Although ncRNAs appear to be good candidates as biomarkers for predicting treatment response and therapeutics for sarcoma, their differential expression across tissues complicates their application. Further research regarding their potential for inhibiting or activating these regulatory molecules to reverse treatment resistance may be useful. Funding: This study’s literature retrieval was supported financially by the 345 Talent Project of Shengjing Hospital of China Medical University (M0949 to Tao Zhang).

Abstract Background Dysfunction of lacrimal gland (LG) gains increasing attention in patients with thyroid-associated ophthalmopathy (TAO), while the underlying pathological change is still not fully established. This study aimed to evaluate the utility of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in non-invasively detecting microstructural alterations of LG in patients with TAO, as well as in discriminating disease activity. Methods Thirty TAO patients and 15 age- and sex- matched healthy controls, who underwent rs-EPI-based DTI, were retrospectively enrolled. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of LG, and clinical-endocrinological variables were collected and compared. The correlations between FA and ADC values of LG and serum thyroid biochemical markers were also assessed. Results TAO group showed significantly lower FA (P 0.05). The area under receiver operating characteristic curve of FA was significantly greater than that under curve of ADC for discriminating disease activity (0.832 vs. 0.570, P = 0.009). Conclusions rs-EPI-based DTI is a useful tool to characterize the microstructural change of LG in patients with TAO. The derived metrics, particularly FA, can help to reveal disease activity.

As a result of an ongoing survey of microfungi associated with garden and ornamental plants in Qijing, Yunnan, China, several saprobic fungal taxa were isolated from Magnolia grandiflora. Both morphological and combined SSU, LSU, ITS, tef1, and rpb2 locus phylogenetic analyses (maximum-likelihood and Bayesian analyses) were carried out to identify the fungal taxa. Three new species are introduced in Pleosporales, viz., Lonicericola qujingensis (Parabambusicolaceae), Phragmocamarosporium magnoliae, and Periacma qujingensis (Lentitheciaceae). Botryosphaeria dothidea, Diplodia mutila, and Diplodia seriata (in Botryosphaeriaceae) are reported from Magnolia grandiflora for the first time in China. Angustimassarina populi (Amorosiaceae) is reported for the first time on M. grandiflora from China, and this is the first report of a member of this genus outside Europe. Shearia formosa is also reported for the first time on M. grandiflora from China.

Fungi play many roles in different ecosystems. The precise identification of fungi is important in different aspects. Historically, they were identified based on morphological characteristics, but technological advancements such as polymerase chain reaction (PCR) and DNA sequencing now enable more accurate identification and taxonomy, and higher-level classifications. However, some species, referred to as “dark taxa”, lack distinct physical features that makes their identification challenging. High-throughput sequencing and metagenomics of environmental samples provide a solution to identifying new lineages of fungi. This paper discusses different approaches to taxonomy, including PCR amplification and sequencing of rDNA, multi-loci phylogenetic analyses, and the importance of various omics (large-scale molecular) techniques for understanding fungal applications. The use of proteomics, transcriptomics, metatranscriptomics, metabolomics, and interactomics provides a comprehensive understanding of fungi. These advanced technologies are critical for expanding the knowledge of the Kingdom of Fungi, including its impact on food safety and security, edible mushrooms foodomics, fungal secondary metabolites, mycotoxin-producing fungi, and biomedical and therapeutic applications, including antifungal drugs and drug resistance, and fungal omics data for novel drug development. The paper also highlights the importance of exploring fungi from extreme environments and understudied areas to identify novel lineages in the fungal dark taxa.

The effects of copper (Cu)–pH interactions on the levels of hormones and related metabolites (HRMs) in Citrus sinensis leaves and roots were investigated. Our findings indicated that increased pH mitigated Cu toxicity-induced alterations of HRMs, and Cu toxicity increased low-pH-induced alterations of HRMs. Increased pH-mediated decreases in ABA, jasmonates, gibberellins, and cytokinins, increases in (±)strigol and 1-aminocyclopropanecarboxylic acid, and efficient maintenance of salicylates and auxins homeostasis in 300 μM Cu-treated roots (RCu300); as well as efficient maintenance of hormone homeostasis in 300 μM Cu-treated leaves (LCu300) might contribute to improved leaf and root growth. The upregulation of auxins (IAA), cytokinins, gibberellins, ABA, and salicylates in pH 3.0 + 300 μM Cu-treated leaves (P3CL) vs. pH 3.0 + 0.5 μM Cu-treated leaves (P3L) and pH 3.0 + 300 μM Cu-treated roots (P3CR) vs. pH 3.0 + 0.5 μM Cu-treated roots (P3R) might be an adaptive response to Cu toxicity, so as to cope with the increased need for reactive oxygen species and Cu detoxification in LCu300 and RCu300. Increased accumulation of stress-related hormones (jasmonates and ABA) in P3CL vs. P3L and P3CR vs. P3R might reduce photosynthesis and accumulation of dry matter, and trigger leaf and root senescence, thereby inhibiting their growth.

Purpose: To evaluate the value of MRI-based texture analysis of extraoc ular muscle (EOM) and orbital fat (OF) in monitoring and predicting the res ponse to glucocorticoid (GC) therapy in patients with thyroid-associated ophthalmopathy (TAO). Methods: Thirty-seven active and moderate-to-severe TAO patients (respo nders, n = 23; unresponders, n = 14) were retrospectively enrolled. MRI-based texture parameters (entropy, uniformity, skewness and kurtosis) of EOM and OF were measured before and after GC therapy, and compared between groups. Correlations between the changes of clinical activity score (CAS) and imaging parameters before and after treatment were assessed. Receiver operating characteristic curves were used to evaluate the predictive value of identified variables. Results: Responsive TAOs showed significantly decreased entropy and incr eased uniformity at EOM and OF after GC therapy (P < 0.01), while unresponders showed no significance. Changes of entropy and uniformity at EOM and OF were significantly correlated with changes of CAS before and after treatment (P < 0.05). Responders showed significantly lower entropy and higher uniformity at EOM than unresponders before treatment (P < 0.01). Entropy and uniformity of EOM and disease duration we re identified as independent predictors for responsive TAOs. Combin ation of all three variables demonstrated optimal efficiency (area under curve, 0.80 2) and sensitivity (82.6%), and disease duration alone demonstrated optimal specifi city (100%) for predicting responsive TAOs. Conclusion: MRI-based texture analysis can reflect histopathological hetero geneity of orbital tissues. It could be useful for monitoring and predicti ng the response to GC in TAO patients.

Background and PurposeAlthough previous neuroimaging studies have demonstrated emotion- and psychology-associated brain abnormalities in patients with thyroid-associated ophthalmopathy (TAO), the changes of brain functional connectivity in TAO were seldom focused. We aimed to investigate interregional and intraregional functional interactions in patients with TAO by using resting-state functional MRI (rs-fMRI) with long- and short-range functional connectivity density (FCD) analysis.MethodsThirty patients with TAO and 30 well-matched healthy controls (HCs) were recruited in our study. Long- and short-range FCD values were calculated and compared between the two groups. Correlations between long- and short-range FCD values and clinical indicators were analyzed.ResultsCompared with HCs, patients with showed both increased long- and short-range FCDs in the left middle frontal gyrus (MFG), orbital part of superior frontal gyrus (ORBsup), and dorsolateral part of superior frontal gyrus (SFGdor); meanwhile, both decreased long- and short-range FCDs in bilateral postcentral gyrus (PoCG), left superior parietal gyrus (SPG), and inferior parietal (IPL). In addition, patients with TAO showed increased short-range FCD in the right SFGdor, bilateral medial part of superior frontal gyrus (SFGmed), left orbital part of middle frontal gyrus (ORBmid), and orbital part of inferior frontal gyrus (ORBinf), as well as decreased short-range FCD in the right supplementary motor area (SMA) and the left paracentral lobule (PCL) than HCs. Moreover, the short-range value in the left SFGdor showed a negative correlation with Montreal Cognitive Assessment (MoCA) score (r = −0.501, p = 0.005).ConclusionOur findings complemented the functional neural mechanism of TAO, and provided potential neuroimaging markers for assessing the psychiatric, visual, and emotional disturbances in patients with TAO.

‘Xuegan’ (Citrus sinensis) seedlings were fertilized 6 times weekly for 24 weeks with 0.5 or 350 μM CuCl2 and 2.5, 10 or 25 μM H3BO3. Cu-toxicity increased Cu uptake per plant (UPP) and Cu concentrations in leaves, stems and roots, decreased water uptake and phosphorus, nitrogen, calcium, magnesium, potassium, sulfur, boron and iron UPP, and increased the ratios of magnesium, potassium, calcium and sulfur UPP to phosphorus UPP and the ratios of leaf magnesium, potassium and calcium concentrations to leaf phosphorus concentration. Many decaying and dead fibrous roots occurred in Cu-toxic seedlings. Cu-toxicity-induced alterations of these parameters and root damage decreased with the increase of boron supply. These results demonstrated that B supplementation lowered Cu uptake and its concentrations in leaves, stems and roots and subsequently alleviated Cu-toxicity-induced damage to root growth and function, thus improving plant nutrient (decreased Cu uptake and efficient maintenance of the other nutrient homeostasis and balance) and water status. Further analysis indicated that the improved nutrition and water status contributed to the boron-mediated amelioration of Cu-toxicity-induced inhibition of seedlings, decline of leaf pigments, large reduction of leaf CO2 assimilation and impairment of leaf photosynthetic electron transport chain revealed by greatly altered chlorophyll a fluorescence (OJIP) transients, reduced maximum quantum yield of primary photochemistry (Fv/Fm), quantum yield for electron transport (ETo/ABS) and total performance index (PIabs,total), and elevated dissipated energy per reaction center (DIo/RC). To conclude, our findings corroborate the hypothesis that B-mediated amelioration of Cu-toxicity involved reduced damage to roots and improved nutrient and water status. Principal component analysis showed that Cu-toxicity-induced changes of above physiological parameters generally decreased with the increase of B supply and that B supply-induced alterations of above physiological parameters was greater in 350 μM Cu-treated than in 0.5 μM Cu-treated seedlings. B and Cu had a significant interactive influence on C. sinensis seedlings.

Purpose: Thyroid-associated ophthalmopathy (TAO) is a debilitating and sight-threatening autoimmune disease that severely impairs patients’ quality of life. Besides the most common ophthalmic manifestations, the emotional and psychiatric disturbances are also usually observed in clinical settings. This study was to investigate the interhemispheric functional connectivity alterations in TAO patients using resting-state functional magnetic resonance imaging (rs-fMRI).Methods: Twenty-eight TAO patients and 22 healthy controls (HCs) underwent rs-fMRI scans. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) values were calculated and compared between the two groups. A linear support vector machine (SVM) classifier was used to examine the performance of static and dynamic VMHC differences in distinguishing TAOs from HCs.Results: Compared with HCs, TAOs showed decreased static VMHC in lingual gyrus (LG)/calcarine (CAL), middle occipital gyrus, postcentral gyrus, superior parietal lobule, inferior parietal lobule, and precuneus. Meanwhile, TAOs demonstrated increased dynamic VMHC in orbitofrontal cortex (OFC). In TAOs, static VMHC in LG/CAL was positively correlated with visual acuity (r = 0.412, P = 0.036), whilst dynamic VMHC in OFC was positively correlated with Hamilton Anxiety Rating Scale (HARS) score (r = 0.397, P = 0.044) and Hamilton Depression Rating Scale (HDRS) score (r = 0.401, P = 0.042). The SVM model showed good performance in distinguishing TAOs from HCs (area under the curve, 0.971; average accuracy, 94%).Conclusion: TAO patients had altered static and dynamic VMHC in the occipital, parietal, and orbitofrontal areas, which could serve as neuroimaging prediction markers of TAO.

The contribution of reactive oxygen species (ROS) and methylglyoxal (MG) formation and removal in high-pH-mediated alleviation of plant copper (Cu)-toxicity remains to be elucidated. Seedlings of sweet orange (Citrus sinensis) were treated with 0.5 (non-Cu-toxicity) or 300 (Cu-toxicity) μM CuCl2 × pH 4.8, 4.0, or 3.0 for 17 weeks. Thereafter, superoxide anion production rate; H2O2 production rate; the concentrations of MG, malondialdehyde (MDA), and antioxidant metabolites (reduced glutathione, ascorbate, phytochelatins, metallothioneins, total non-protein thiols); and the activities of enzymes (antioxidant enzymes, glyoxalases, and sulfur metabolism-related enzymes) in leaves and roots were determined. High pH mitigated oxidative damage in Cu-toxic leaves and roots, thereby conferring sweet orange Cu tolerance. The alleviation of oxidative damage involved enhanced ability to maintain the balance between ROS and MG formation and removal through the downregulation of ROS and MG formation and the coordinated actions of ROS and MG detoxification systems. Low pH (pH 3.0) impaired the balance between ROS and MG formation and removal, thereby causing oxidative damage in Cu-toxic leaves and roots but not in non-Cu-toxic ones. Cu toxicity and low pH had obvious synergistic impacts on ROS and MG generation and removal in leaves and roots. Additionally, 21 (4) parameters in leaves were positively (negatively) related to the corresponding root parameters, implying that there were some similarities and differences in the responses of ROS and MG metabolisms to Cu–pH interactions between leaves and roots.

Globally, lung cancer is the most commonly diagnosed cancer and carries with it the greatest mortality rate, with 5-year survival rates varying from 4–17% depending on stage and geographical differences. For decades, researchers have studied disease mechanisms, occurrence rates and disease development, however, the mechanisms underlying disease progression are not yet fully elucidated, thus an increased understanding of disease pathogenesis is key to developing new strategies towards specific disease diagnoses and targeted treatments. Circular RNAs (circRNAs) are a class of non-coding RNA widely expressed in eukaryotic cells, and participate in various biological processes implicated in human disease. Recent studies have indicated that circRNAs both positively and negatively regulate lung cancer cell proliferation, migration, invasion and apoptosis. Additionally, circRNAs could be promising biomarkers and targets for lung cancer therapies. This review systematically highlights recent advances in circRNA regulatory roles in lung cancer, and sheds light on their use as potential biomarkers and treatment targets for this disease.

Climate change is a major factor influencing the species distribution and population diversity of living creatures. In this study, the ecological niche model (ENM) MaxEnt was used to evaluate habitat suitability and predict potential habitats of two sympatric fig species, i.e., Ficus squamosa and F. heterostyla, in the Xishuangbanna region of China. Results indicated that mean diurnal range, isothermality, cation exchange capacity (at pH 7), and temperature seasonality were key variables influencing habitat suitability for F. squamosa. However, temperature seasonality and precipitation of the driest quarter showed the greatest contributions to F. heterostyla distribution. During the current period, the habitat suitability distributions of both Ficus species were considerably higher than known occurrences. In the future, potentially suitable distribution areas for both species will reduce overall across the whole study area, although some expansion may occur by 2070. Niche overlap of suitable areas for both species was initially high and then declined in the current period and future epochs in the RCP 2.6 scenario, but increased in the RCP 8.5 scenario. In short, the responses of both Ficus species to climate change differed. Thus, specific actions such as ex situ conservation and assisted migration may be needed to conserve both species.

PurposeThe purpose of the study was to investigate the brain functional alteration in patients with thyroid-associated ophthalmopathy (TAO) by evaluating the spontaneous neural activity changes using resting-state functional magnetic resonance imaging (rs-fMRI) with the amplitude of low-frequency fluctuation (ALFF) method.Materials and MethodsThe rs-fMRI data of 30 TAO patients (15 active and 15 inactive) and 15 healthy controls (HCs) were included for analyses. The ALFF values were calculated and compared among groups. Correlations between ALFF values and clinical metrics were assessed.ResultsCompared with HCs, active TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, and cuneus. Compared with inactive TAOs, active TAOs showed significantly increased ALFF values in the bilateral precuneus. Additionally, inactive TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, cuneus, and bilateral precuneus than HCs. The ALFF value in the right precuneus of TAOs was positively correlated with clinical activity score (r = 0.583, P < 0.001) and Mini-Mental State Examination (MMSE) score (r = 0.377, P = 0.040), and negatively correlated with disease duration (r = −0.382, P = 0.037). Moreover, the ALFF value in the left middle occipital gyrus of TAOs was positively correlated with visual acuity (r = 0.441, P = 0.015).ConclusionTAO patients had altered spontaneous brain activities in the left occipital lobe and bilateral precuneus. The neuropsychological aspect of the disease should be noticed during clinical diagnosis and treatment.

Low pH-induced alterations in gene expression profiles and organic acids (OA) and free amino acid (FAA) abundances were investigated in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] leaves. We identified 503 downregulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OA biosynthesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen compounds, proteins, and FAAs in leaves, which might be conducive to maintaining energy homeostasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses to phosphate starvation, including phosphate recycling, lipid remodeling, and phosphate transport, thus enhancing leaf acid-tolerance. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid, and pyroglutamic acid), but it impaired the pentose phosphate pathway and VE and secondary metabolite biosynthesis and downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase, and 2-alkenal reductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.

During the ongoing investigation of bambusicolous ascomycetous fungi in Yunnan, China, 24 specimens belonging to the family Roussoellaceae were collected and identified based on morphological features and phylogenetic support. Maximum-likelihood (ML) analyses and Bayesian analyses were generated based on the combined data set of ITS, LSU, tef1, and rpb2 loci. The phylogenetic analyses revealed four novel lineages in Roussoella s. str.; thus, we introduced four new species viz., Roussoella multiloculate sp. nov., R. papillate sp. nov., R. sinensis sp. nov., and R. uniloculata sp. nov. Their morphological characters were compared with the known Roussoella taxa, which lack sequence data in the GenBank. Asexual morphs of R. kunmingensis and R. padinae were recorded from dead bamboo culms in China (from the natural substrates) for the first time. Neoroussoella bambusae, Roussoella japanensis, R. nitidula, R. padinae, R. scabrispora, and R. tuberculate were also reported as the first records from China. All new taxa are described and illustrated in detail. Plates are provided for new reports.

Background. Accurate staging of patients with thyroid-associated ophthalmopathy (TAO) is crucial for clinical decision. Full cognition of pathologic changes and staging TAO using conventional T2-weighted imaging is still limited. Purpose. To investigate the feasibility of using T1 mapping to evaluate changes of extraocular muscles (EOMs) in TAO patients, as well as to compare T1 mapping and conventional T2-weighted imaging in staging TAO. Materials and Methods. Forty TAO patients were retrospectively enrolled. “Hot spot” and “cold spot” T1 relaxation times (T1RTHS and T1RTCS) of EOMs, as well as conventionally applied highest signal intensity ratio (SIR) of EOMs, were measured and compared between active and inactive groups. Results. T1RTCS and SIR were significantly higher in active TAOs than in the inactive ones (P

Since the essentiality of boron (B) to plant growth was reported nearly one century ago, the implication of B in physiological performance, productivity and quality of agricultural products, and the morphogenesis of apical meristem in plants has widely been studied. B stresses (B deficiency and toxicity), which lead to atrophy of canopy and deterioration of Citrus fruits, have long been discovered in citrus orchards. This paper reviews the research progress of B stresses on Citrus growth, photosynthesis, light use efficiency, nutrient absorption, organic acid metabolism, sugar metabolism and relocation, and antioxidant system. Moreover, the beneficial effects of B on plant stress tolerance and further research in this area were also discussed.

Limited data are available on the physiological responses of Citrus to nitrogen (N) deficiency. ‘Xuegan’ (Citrus sinensis (L.) Osbeck) and ‘Shantian pummelo’ (Citrus grandis (L.) Osbeck) seedlings were fertilized with nutrient solution at a N concentration of 0, 5, 10, 15 or 20 mM for 10 weeks. N deficiency decreased N uptake and N concentration in leaves, stems and roots and disturbed nutrient balance and homeostasis in plants, thus inhibiting plant growth, as well as reducing photosynthetic pigment levels and impairing thylakoid structure and photosynthetic electron transport chain (PETC) in leaves, hence lowering CO2 assimilation. The imbalance of nutrients intensified N deficiency’s adverse impacts on biomass, PETC, CO2 assimilation and biosynthesis of photosynthetic pigments. Citrus displayed adaptive responses to N deficiency, including (a) elevating the distributions of N and other elements in roots, as well as root dry weight (DW)/shoot DW ratio and root-surface-per-unit volume and (b) improving photosynthetic N use efficiency (PNUE). In general, N deficiency had less impact on biomass and photosynthetic pigment levels in C. grandis than in C. sinensis seedlings, demonstrating that the tolerance of C. grandis seedlings to N deficiency was slightly higher than that of C. sinensis seedlings, which might be related to the higher PNUE of the former.

Abstract Bisphenol A (BPA), one of 23 most important endocrine disrupting chemicals, was efficiently removed and sequentially photodegraded by a zirconium-porphyrin metal–organic framework (MOF) catalyst under visible light for water treatment. Well control of photodegradation allows the kinetic separation of adsorption step and photodegradation step. Ultrahigh adsorption uptake of 487.69 ± 8.37 mg g−1 is observed, while efficient photodegradation could be observed within 20 min at the rate of 0.004 mg min−1. The synergetic effect boosts the photocatalytic efficiency and confirms that the catalysis happens inside the MOF pores other than in the solution phase. Furthermore, the mechanism was elucidated by diverse control experiments, such as in the conditions of 1O2 scavenger, in darkness and with the changes of light sensitizing ligands. It confirmed that BPA was oxidized by the 1O2 which was generated from porphyrin ligand within MOFs under visible-light. The excellent reusability and wide range of suitable pH range make the Zr-porphyrin MOFs practical for the photocatalytic water treatment processes.

Limited data are available on the sulfur (S)-mediated-alleviation of aluminum (Al)-toxicity in higher plants. Citrus grandis seedlings were irrigated for 18 weeks with 0.5 mM MgSO4 or 0.5 mM MgSO4 + 0.5 mM Na2SO4, and 0 (−Al) or 1 mM AlCl3·6H2O (+Al, Al-toxicity). Under Al-toxicity, S decreased the level of Al in leaves; increased the relative water content (RWC) of roots and leaves, the contents of phosphorus (P), calcium (Ca) and magnesium (Mg) per plant, the dry weights (DW) of roots and shoots, the ratios of root DW/shoot DW, and the Al-induced secretion of citrate from root; and alleviated the Al-induced inhibition of photosynthesis via mitigating the Al-induced decrease of electron transport capacity resulting from the impaired photosynthetic electron transport chain. In addition to decreasing the Al-stimulated H2O2 production, the S-induced upregulation of both S metabolism-related enzymes and antioxidant enzymes also contributed to the S-mediated-alleviation of oxidative damage in Al-treated roots and leaves. Decreased transport of Al from roots to shoots and relatively little accumulation of Al in leaves, and increased leaf and root RWC and P, Ca, and Mg contents per plant might also play a role in the S-mediated-alleviation of Al-toxicity.

Objective: To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Methods: Between 2019 and 2022, 32 patients with TAO and 23 healthy controls underwent pre-therapy MRI in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. At 3 months after end of therapy, 26 patients were available for rescanned MRI. VBM, ALFF, and ReHo were used to evaluate the brain structural and functional differences. Results: Before therapy, TAO patients showed significantly decreased gray matter volume (GMV) in the left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex and lower values in bilateral cuneus. Patients also showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased GMV in the left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, and increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased GMV in left ORBsup was observed in post-therapy TAO patients. Conclusion: Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to deeper understanding of the pathophysiological mechanism behind TAO. [ABSTRACT FROM AUTHOR]