The progress and prospect of sentinel lymph node mapping in endometrial carcinoma.

Sentinel lymph node (SLN) refers to the initial site of the lymphatic drainage from a primary tumor area. Identifying the SLN and analyzing tumor involvement can predict the status of the remaining lymph nodes. Accordingly, sentinel lymph node mapping (SLN mapping) has been brought up and widely applied to cancer therapy for its illuminating role in clinical lymph node resection. Sufficient information to guide surgical pathological staging and adjuvant treatment in endometrial cancer can be rendered by SLN mapping, hence minimizing surgery injury and reducing the incidence of complications. Evidence suggests that using SLN mapping does not affect progression-free survival (PFS) and overall survival (OS) of endometrial cancer patients. Furthermore, there is increasing evidence that using SLN mapping has a high detection rate (DR), sensitivity, and negative predictive value (NPV) for patients with early-stage lower-risk endometrial cancer. This review aims to systematically summarize the advances and application prospects of SLN mapping in endometrial cancer, with an expectation of furnishing reference for the clinical application.

Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases: Expanding the Therapeutic Approaches by Plant-Derived Natural Products.

Mitochondria are the primary source of energy production in neurons, supporting the high energy consumption of the nervous system. Inefficient and dysfunctional mitochondria in the central nervous system have been implicated in neurodegenerative diseases. Therefore, targeting mitochondria offers a new therapeutic opportunity for neurodegenerative diseases. Many recent studies have proposed that plant-derived natural products, as pleiotropic, safe, and readily obtainable sources of new drugs, potentially treat neurodegenerative diseases by targeting mitochondria. In this review, we summarize recent advances in targeting mitochondria in neurotherapeutics by employing plant-derived natural products. We discuss the mechanism of plant-derived natural products according to their mechanism of action on mitochondria in terms of regulating biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability, as well as repairing damaged mitochondria. In addition, we discuss the potential perspectives and challenges in developing plant-derived natural products to target mitochondria, highlighting the clinical value of phytochemicals as feasible candidates for future neurotherapeutics.

First Report of Bayberry Leaf Blight Caused by Pestalotiopsis kenyana in Zhejiang Province, China.

Weizhi Xun and Changwang Wu contributed equally to this work In October 2020, bayberry (Myrica rubra (Lour.) S. et Zucc.) leaves that beginning to wither were collected in Wencheng County (N27°50', E120°03'). In the county, 4,120 ha of bayberry were planted, of which 58% were affected by the disease, and the severity of leaf disease per plant was 5 to25%. Bayberry leaves leaves were intensely green at first, then gradually turned yellow and brown,and completely withered. The leaves did not fall off at the beginning of the symptoms, but did fall after 1 to 2 months. To identify the pathogen, 50 diseased leaves with typical symptoms were collected from 10 diseased trees. Leaves with necrotic-tissue were firstly washed with sterilized water, and then tissue at the disease-/ healthy-tissuejunction removed with sterile surgical scissors. The tissues were soaked in 75% ethanol for 30 s, followed by 5% sodium hypochlorite solution for 3 to 4 min, rinsed with sterilized water 4 times, and placed on sterilized filter paper. The tissue was placed on PDA medium and cultured in an incubator at 25℃ (Nouri et al. 2019). After the colonies grew around the tissue, mycelia with the same morphology was selected and placed on fresh PDA. A pure culture of the pathogen was obtained after repeating the last process several times. The isolatedcolonies were white, with a round edge and a light-yellow back. Conidia were straight or slightly curved, with 3 to 4 septations. The internal transcribed spacer (ITS) regin translation elongation factor 1-α gene (TEF1-α), and beta-tubulin gene (ß-TUB)(Chaiwan et al. 2020; Li et al. 2021; Chen et al. 2020; Chen et al. 2018) of the two strains were amplified and sequenced, and the sequences were uploaded to Gen bank (GenBank accession number.ACCC 35162: ITS OP891011, TEF1-α OP903533, ß-TUB OP903531; ACCC 35163: ITS OP891012, ß-TUB OP903534, TEF1-α OP903532). BLAST alignment indicated that the ITS sequence of strain ACCC 35162 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.87% identity with KX895323.1; the ITS sequence of strain ACCC 35163 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.86% identity with KX895323.1. A Phylogenetic tree using maximum likelihood/rapid bootstrapping run on XSEDE based on the above three sequences inferred that the two strains were identical to P. kenyana (Miller et al. 2010). The strain was preserved in the Agricultural Culture Collection of China (Preservation numbers: ACCC 35162, ACCC 35163). Following Koch's rule, six healthy plants leaves were inoculated with conidial suspensions (106 conidia mL-1) and mycelial plugs (5 mm)，and then placed in an artificial climate chamber (25℃, 90% humidity, 16-h light), sterile PDA and sterile water were used as blank controls. The same treatment was applied to fresh bayberry leaves under laboratory conditions, and brown spots were observed after three days. There were no symptoms in the control group. The experimental symptoms were similar to those in the field. Using the previous method, the same fungus was reisolated from the diseased leaves and again identified as P. kenyana. As far as we know, this is the first report causing disease on P. kenyana infecting bayberry in China, this disease seriously affected the yield and quality of bayberry and caused economic losses to farmers.

Prelithiation of Lithium Peroxide for Silicon Anode: Achieving a High Activation Rate.

The use of lithium peroxide (Li2O2) as a cost-effective low-weight prelithiation cathode additive was successfully demonstrated. Through a series of studies on the chemical stability of Li2O2 and the activation process of Li2O2 on the cathode, we revealed that Li2O2 is more compatible with conventional electrolyte and cathode laminate slurry than lithium oxide. Due to the significantly smaller size of commercial Li2O2, it can be used directly as a cathode additive. Moreover, the activation of Li2O2 on the cathode leads to the impedance growth of the cathode possibly resulting from the release of dioxygen and evacuation of Li2O2 inside the cathode. With the introduction of a new Li2O2 spread-coating technique on the cathode, the capacity loss was suppressed. Si||NMC full cells using Li2O2 spread-coated cathode demonstrated a highly promising activation rate of Li2O2 and significantly enhanced specific capacity and cycling stability compared to the uncoated full cells.

First Report of Alternaria alternata Causing White Leaf Spot on Allium tuberosum in China.

Puding County is the major Allium tuberosum growing area in Guizhou Province of China. In 2019, white leaf spots were observed on Allium tuberosum in Puding County (26.31°N, 105.64°E). The white spots, ranging from elliptic to irregular in shape, first appeared on leaf tips. With disease aggravation, spots gradually coalesced, forming necrotic patches with yellow margins causing leaf necrosis; sometimes there was gray mold on dead leaves. The incidence of the diseased leaf rate was estimated to be 27-48%. To identify the pathogenic agent, 150 leaf tissues (5 mm × 5 mm) were obtained from disease-healthy junctions of 50 diseased leaves. Leaf tissues were disinfected in 75% ethanol for 30 s, soaked in 0.5% sodium hypochlorite for 5 min, and flushed three times with sterile water, before being placed on potato dextrose agar (PDA) in the dark at 25 °C. When colonies appeared, the mycelial tips were picked and placed on new PDA. Purified fungus was obtained after repeating this last step several times. The colonies were grayish-green with white round margins. Conidiophores (2.7-4.5 µm × 27-81 µm) were brown, straight, or flexuous with branches and septa. Conidia (8-34 µm × 5-16 µm) were brown, with 0-5 transverse septa and 0-4 longitudinal septa. The 18S nuclear ribosomal DNA (nrDNA; SSU), 28S nrDNA (LSU), RNA polymerase II second largest subunit (RPB2), internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and translation elongation factor 1-alpha (TEF-α) (Woudenberg et al. 2013) were amplified and sequenced. The sequences were deposited in GenBank (ITS: OP703616, LSU: OP860684, SSU: OP860685, GAPDH: OP902372, RPB2: OP902373, TEF1-α: OP902374). According to BLAST analysis, the ITS, LSU, GAPDH, RPB2, SSU, and TEF1-α of the straishowed 100% (689 of 731 base pairs; bp), 100% (916 of 938 bp), 100% (579 of 600 bp), 100% (946 of 985 bp), 100% (1093 of 1134 bp), and 100% (240 of 240 bp) sequence identity to those of Alternaria alternata (ITS: LC440581.1, LSU: KX609781.1, GAPDH: MT109295.1, RPB2: MK605900.1, SSU: ON055699.1 and TEF1-α: OM220081.1). A phylogenetic tree was constructed using PAUP4 and the maximum parsimony method with 1000 replicas of bootstrapping for all datasets. According to morphological characteristics and phylogenetic analysis, FJ-1 was identified as Alternaria alternata (Simmons 2007, Woudenberg et al. 2015). The strain was preserved in the Agricultural Culture Collection of China (preservation number: ACC39969). To determine the pathogenicity of Alternaria alternata against Allium tuberosum, wounded healthy leaves were inoculated with a conidial suspension (106 conidial/mL) and round mycelial plugs (4mm). Sterile agar PDA plugs with no mycelium or sterile water were inoculated as negative controls. Three days later, white spots appeared on the wounded leaves inoculated with mycelial plugs or conidial suspension. However, the symptoms caused by conidial suspensions were weaker than those caused by mycelial plugs. No symptoms were observed in the control group. The experimental symptoms were consistent with the phenomena observed in the field. The same fungus was reisolated from necrotic lesions and identified as Alternaria alternata using the method described above. To our knowledge, this is the first report of Alternaria alternata causing white leaf spots on Allium tuberosum in China, a disease seriously affected the yield and quality of Allium tuberosum and caused economic losses to farmers. Reference: Simmons EG (2007) Alternaria: an identification manual. CBS Fungal Biodiversity Centre, Utrecht, the Netherlands. Woudenberg JHC, Groenewald JZ, Binder M, Crous PW ( 2013) Alternaria redefined. Stud Mycol, 75: 171-212. https://doi.org/10.3114/sim0015. Woudenberg JHC, Seidl MF, Groenewald JZ, Vries M de, Stielow JB, Thomma BPHJ, Crous PW (2015) Alternaria section Alternaria: Species, formae speciales or pathotypes? Stud Mycol, 82:1-21. https://doi.org/10.1016/j.simyco.2015.07.001.

The multifaceted roles of natural products in mitochondrial dysfunction.

Mitochondria are the primary source of energy production in cells, supporting the metabolic demand of tissue. The dysfunctional mitochondria are implicated in various diseases ranging from neurodegeneration to cancer. Therefore, regulating dysfunctional mitochondria offers a new therapeutic opportunity for diseases with mitochondrial dysfunction. Natural products are pleiotropic and readily obtainable sources of therapeutic agents, which have broad prospects in new drug discovery. Recently, many mitochondria-targeting natural products have been extensively studied and have shown promising pharmacological activity in regulating mitochondrial dysfunction. Hence, we summarize recent advances in natural products in targeting mitochondria and regulating mitochondrial dysfunction in this review. We discuss natural products in terms of their mechanisms on mitochondrial dysfunction, including modulating mitochondrial quality control system and regulating mitochondrial functions. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products, emphasizing the potential value of natural products in mitochondrial dysfunction.

Nano-Econazole Enhanced PD-L1 Checkpoint Blockade for Synergistic Antitumor Immunotherapy against Pancreatic Ductal Adenocarcinoma.

Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). Although econazole has shown promise in inhibiting PDAC growth, its poor bioavailability and water solubility limit its potential as a clinical therapy for PDAC. Furthermore, the synergistic role of econazole and biliverdin in immune checkpoint blockade therapy in PDAC remains elusive and challenging. Herein, a chemo-phototherapy nanoplatform is designed by which econazole and biliverdin can be co-assembled (defined as FBE NPs), which significantly improve the poor water solubility of econazole and enhance the efficacy of PD-L1 checkpoint blockade therapy against PDAC. Mechanistically, econazole and biliverdin are directly released into the acidic cancer microenvironment, to activate immunogenic cell death via biliverdin-induced PTT/PDT and boost the immunotherapeutic response of PD-L1 blockade. In addition, econazole simultaneously enhances PD-L1 expression to sensitize anti-PD-L1 therapy, leading to suppression of distant tumors, long-term immune memory effects, improved dendritic cell maturation, and tumor infiltration of CD8+ T lymphocytes. The combined FBE NPs and α-PDL1 show synergistic antitumor efficacy. Collectively, FBE NPs show excellent biosafety and antitumor efficacy by combining chemo-phototherapy with PD-L1 blockade, which has promising potential in a precision medicine approach as a PDAC treatment strategy.

Synergistic Transition-Metal Selenide Heterostructure as a High-Performance Cathode for Rechargeable Aluminum Batteries.

We synthesize and characterize a rechargeable aluminum battery cathode material composed of heterostructured Co3Se4/ZnSe embedded in a hollow carbon matrix. This heterostructure is synthesized from a metal-organic framework composite, in which ZIF-8 is grown on the surface of ZIF-67 cube. Both experimental and theoretical studies indicate that the internal electric field across the heterostructure interface between Co3Se4 and ZnSe promotes the fast transport of electron and Al-ion diffusion. As a result, the heterostructured Co3Se4/ZnSe demonstrates superior specific capacity and cycle stability compared to the single-phase Co3Se4 and ZnSe cathode materials.

The diagnostic and therapeutic prospects of exosomes in ovarian cancer.

Exosomes are nano-sized vesicles derived from the endosomal system and are involved in many biological and pathological processes. Emerging evidence has demonstrated that exosomes with cell-specific constituents are associated with the tumorigenesis and progression of ovarian cancer. Therefore, exosomes derived from ovarian cancers can be potential diagnostic biomarkers and therapeutic targets. In this review, we briefly present the biological characteristics of exosomes and the recent advances in isolating and detecting exosomes. Furthermore, we summarise the many functions of exosomes in ovarian cancer, hoping to provide a theoretical basis for clinical applications of exosomes in the diagnosis and treatment of ovarian cancer.

A nanoplatform reshaping intracellular osmolarity and redox homeostasis against colorectal cancer.

Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemoresistance remaining a major obstacle in CRC treatment. Sodium persulfate (Na2S2O8) is a novel agent capable of producing •SO4- and Na+ for chemodynamic therapy (CDT). This can induce pyroptosis and ferroptosis instead of conventional apoptosis in tumor cells. Meanwhile, IR780-iodide (IR780), as an excellent phototherapy agent, can generate hyperthermia and generate a large amount of reactive oxygen species (ROS) to synergize with the CDT of Na2S2O8, with potential to overcome chemoresistance in CRC. However, the low stability of Na2S2O8 and the poor solubility of IR780 limit their applications in the medical field. Accordingly, for the first time, D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), Na2S2O8 and IR780 were rationally designed in a cascade-amplifying nanoplatform (Na2S2O8-IR780 NPs) via a co-assembly strategy. Combining Na2S2O8 and IR780 in a nanoplatform improves the stability of Na2S2O8 and the solubility of IR780. As a result, the Na2S2O8-IR780 NPs exhibited excellent antitumor efficacy in CRC cell lines and five chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. This photo-chemodynamic nanoplatform provides a brand-new paradigm by manipulating osmolarity and redox homeostasis to overcome chemo-resistance and holds great potential for the treatment of CRC.

Altered dynamic spontaneous neural activity in minimal hepatic encephalopathy.

Background and aims: Abnormal regional neural activity has been identified by the analysis of the static amplitude of low-frequency fluctuation (ALFF) in the setting of minimal hepatic encephalopathy (MHE). Brain activity is highly dynamic. This work sought to evaluate the temporal variability of ALFF to reveal MHE-related alterations in the dynamics of spontaneous neural activity. Methods: A total of 29 healthy controls and 49 patients with cirrhosis [including 20 patients with MHE and 29 patients without MHE (NHE)] who underwent resting-state functional magnetic resonance imaging and Psychometric Hepatic Encephalopathy Score (PHES) examination were enrolled in this investigation. Utilizing a sliding-window approach, we calculated the dynamic ALFF (dALFF) variability to reflect the temporal dynamics of regional neural activity. An analysis of the correlation between dALFF variability and PHES was performed, and receiver operating characteristic (ROC) curve analysis to determine the potential of the dALFF variability index in identifying MHE was completed. Results: The dALFF variability in the bilateral precuneus/posterior cingulate gyrus and left middle frontal gyrus progressively decreased from NHE to MHE group. In cirrhotic patients, the value of dALFF variability in the bilateral precuneus/posterior cingulate gyrus was positively correlated with their neurocognitive performance (r = 0.383 and P = 0.007). The index of dALFF variability in the bilateral precuneus/posterior cingulate gyrus could be used to distinguish NHE and MHE patients, with moderate power (area under the ROC curve = 0.712 and P = 0.012). Conclusion: Our findings highlight the existence of aberrant dynamic brain function in MHE, which could underlie the neural basis of cognitive impairments and could be associated with the development of the disease. Analyzing dALFF could facilitate new biomarker identification for MHE.

Drug repurposing in cancer neuroscience: From the viewpoint of the autophagy-mediated innervated niche.

Based on the bidirectional interactions between neurology and cancer science, the burgeoning field "cancer neuroscience" has been proposed. An important node in the communications between nerves and cancer is the innervated niche, which has physical contact with the cancer parenchyma or nerve located in the proximity of the tumor. In the innervated niche, autophagy has recently been reported to be a double-edged sword that plays a significant role in maintaining homeostasis. Therefore, regulating the innervated niche by targeting the autophagy pathway may represent a novel therapeutic strategy for cancer treatment. Drug repurposing has received considerable attention for its advantages in cost-effectiveness and safety. The utilization of existing drugs that potentially regulate the innervated niche via the autophagy pathway is therefore a promising pharmacological approach for clinical practice and treatment selection in cancer neuroscience. Herein, we present the cancer neuroscience landscape with an emphasis on the crosstalk between the innervated niche and autophagy, while also summarizing the underlying mechanisms of candidate drugs in modulating the autophagy pathway. This review provides a strong rationale for drug repurposing in cancer treatment from the viewpoint of the autophagy-mediated innervated niche.

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies.

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.

Performance Leap of Lithium Metal Batteries in LiPF6 Carbonate Electrolyte by a Phosphorus Pentoxide Acid Scavenger.

Phosphorus pentoxide (P2O5) is investigated as an acid scavenger to remove the acidic impurities in a commercial lithium hexafluorophosphate (LiPF6) carbonate electrolyte to improve the electrochemical properties of Li metal batteries. Nuclear magnetic resonance (NMR) measurements reveal the detailed reaction mechanisms of P2O5 with the LiPF6 electrolyte and its impurities, which removes hydrogen fluoride (HF) and difluorophosphoric acid (HPO2F2) and produces phosphorus oxyfluoride (POF3), OF2P-O-PF5- anions, and ethyl difluorophosphate (C2H5OPOF2) as new electrolyte species. The P2O5-modified LiPF6 electrolyte is chemically compatible with a Li metal anode and LiNi0.6Mn0.2Co0.2O2 (NMC622) cathode, generating a POxFy-rich solid electrolyte interphase (SEI) that leads to highly reversible Li electrodeposition, while eliminating transition metal dissolution and cathode particle cracking. The excellent electrochemical properties of the P2O5-modified LiPF6 electrolytes are demonstrated on Li||NMC622 pouch cells with 0.4 Ah capacity, 50 µm Li anode, 3 mAh cm-2 NMC622 cathode, and 3 g Ah-1 electrolyte/capacity ratio. The pouch cells can be galvanostatically cycled at C/3 for 230 cycles with 87.7% retention.

Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy.

To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = -0.458 and P = 0.001; and r = -0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.

Dynamic Alterations in Functional Connectivity Density in Amyotrophic Lateral Sclerosis: A Resting-State Functional Magnetic Resonance Imaging Study.

Background and Aims: Current knowledge on the temporal dynamics of the brain functional organization in amyotrophic lateral sclerosis (ALS) is limited. This is the first study on alterations in the patterns of dynamic functional connection density (dFCD) involving ALS. Methods: We obtained resting-state functional magnetic resonance imaging (fMRI) data from 50 individuals diagnosed with ALS and 55 healthy controls (HCs). We calculated the functional connectivity (FC) between a given voxel and all other voxels within the entire brain and yield the functional connection density (FCD) value per voxel. dFCD was assessed by sliding window correlation method. In addition, the standard deviation (SD) of dFCD across the windows was computed voxel-wisely to measure dFCD variability. The difference in dFCD variability between the two groups was compared using a two-sample t-test following a voxel-wise manner. The receiver operating characteristic (ROC) curve was used to assess the between-group recognition performance of the dFCD variability index. Results: The dFCD variability was significantly reduced in the bilateral precentral and postcentral gyrus compared with the HC group, whereas a marked increase was observed in the left middle frontal gyrus of ALS patients. dFCD variability exhibited moderate potential (areas under ROC curve = 0.753-0.837, all P < 0.001) in distinguishing two groups. Conclusion: ALS patients exhibit aberrant dynamic property in brain functional architecture. The dFCD evaluation improves our understanding of the pathological mechanisms underlying ALS and may assist in its diagnosis.

Functional Annotation of circRNAs in Tea Leaves After Infection by the Tea Leaf Spot Pathogen, Lasiodiplodia theobromae.

Tea leaf spot, caused by Lasiodiplodia theobromae, is an important disease that can seriously decrease the production and quality of tea (Camellia sinensis (L.) O. Kuntze) leaves. The analysis of circular RNA (circRNA) in tea leaves after infection by the pathogen could improve understanding about the mechanism of host-pathogen interactions. In this study, high-performance sequencing of circRNA from C. sinensis Fuding-dabaicha leaves that had been infected with L. theobromae was conducted using the Illumina HiSeq 4000 platform. In total, 192 and 153 differentially expressed circRNAs from tea leaves were significantly up- and downregulated, respectively, after infection with L. theobromae. A gene ontology analysis indicated that the differentially expressed circRNA-hosting genes for DNA binding were significantly enriched. The genes with significantly differential expressions that were annotated in the specified database (S genes) were σ factor E isoform 1, triacylglycerol lipase SDP1, DNA-directed RNA polymerase III subunit 2, WRKY transcription factor WRKY24, and regulator of nonsense transcripts 1 homolog. A Kyoto Encyclopedia of Genes and Genomes analysis indicated that the significantly enriched circRNA-hosting genes involved in the plant-pathogen interaction pathway were Calmodulin-domain protein kinase 5 isoform 1, probable WRKY transcription factor 33, U-box domain-containing protein 35, probable inactive receptor-like protein kinase At3g56050, WRKY transcription factor WRKY24, mitogen-activated protein kinase kinase kinase YODA, SGT1, and protein DGS1. Functional annotation of circRNAs in tea leaves infected by L. theobromae will provide a valuable resource for future research on host-pathogen interactions.

The Sequence and Integrated Analysis of Competing Endogenous RNAs Originating from Tea Leaves Infected by the Pathogen of Tea Leaf Spot, Didymella segeticola.

Tea leaf spot, caused by Didymella segeticola, is an important disease which negatively affects the productivity and the quality of tea leaves. During infection by the pathogen, competing endogenous RNAs (ceRNAs) from tea leaves could contribute to achieving pathogenicity. In this study, circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs), constituting ceRNAs, which share binding sites on microRNAs (miRNAs), and messenger RNAs (mRNAs) from infected and uninfected leaves of tea (Camellia sinensis 'Fuding-dabaicha') were sequenced and analyzed, and the identity and expression levels of the target genes of miRNA-mRNA and miRNA-lncRNA/circRNA were predicted. Analysis indicated that 10 mRNAs were bound by 20 miRNAs, 66 lncRNAs were bound by 40 miRNAs, and 17 circRNAs were bound by 29 miRNAs, respectively. For the regulation modes of ceRNAs, five ceRNA pairs were identified by the correlation analysis of lncRNA-miRNA-mRNA. For instance, expression of the xyloglucan endotransglycosylase gene in infected leaves was downregulated at the level of mRNA through miRNA PC-5p-3511474_3 binding with lncRNA TEA024202.1:MSTRG.37074.1. Gene annotation indicated that expression of this gene was significantly enriched in cell wall biogenesis and in the pathway of plant hormone signal transduction. The functional analysis of ceRNAs isolated from infected tea leaves will provide a valuable resource for future research on D. segeticola pathogenicity.

Redox-sensitive cyclophilin A elicits chemoresistance through realigning cellular oxidative status in colorectal cancer.

Cancer cells utilize rapidly elevated cellular antioxidant programs to accommodate chemotherapy-induced oxidative stress; however, the underlying mechanism remains largely unexplored. Here we screen redox-sensitive effectors as potential therapeutic targets for colorectal cancer (CRC) treatment and find that cyclophilin A (CypA) is a compelling candidate. Our results show that CypA forms an intramolecular disulfide bond between Cys115 and Cys161 upon oxidative stress and the oxidized cysteines in CypA are recycled to a reduced state by peroxiredoxin-2 (PRDX2). Furthermore, CypA reduces cellular reactive oxygen species levels and increases CRC cell survival under insults of H2O2 and chemotherapeutics through a CypA-PRDX2-mediated antioxidant apparatus. Notably, CypA is upregulated in chemoresistant CRC samples, which predicts poor prognosis. Moreover, targeting CypA by cyclosporine A exhibits promising efficacy against chemoresistant CRC when combined with chemotherapeutics. Collectively, our findings highlight CypA as a component of cellular noncanonical antioxidant defense and as a potential druggable therapeutic target to ameliorate CRC chemoresistance.

Abnormal Stability of Dynamic Functional Architecture in Amyotrophic Lateral Sclerosis: A Preliminary Resting-State fMRI Study.

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity. Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis. Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = -0.452 and P = 0.046) in the ALS patients. Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.