PTOV1-AS1 desensitizes colorectal cancer cells to 5-FU through depressing miR-149-5p to activate the positive feedback loop with Wnt/ß-catenin pathway.

5-Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5-Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5-Fluorouracil resistance in colorectal cancer. RT-qPCR and Western blot were used to determine the RNA and protein expression in both cells and exosome. Assays in vitro and in vivo were performed to measure the role of miR-149-5p in colorectal cancer cells. RIP, luciferase activity report, and RNA pulldown assay were applied to detect the association of PTOV1-AS1, SUV39H1, miR-149-5p, and FOXM1. MiR-149-5p was down-expressed in 5-Fluorouracil-resistant cells. MiR-149-5p enhanced the effectiveness of 5-Fluorouracil both in vitro and in vivo. Sensitive colorectal cancer cells released exosomal miR-149-5p to sensitize resistant cells to chemotherapy. Mechanistically, miR-149-5p targeted the FOXM1 to inactivate Wnt/ß-catenin pathway, and PTOV1-AS1 recruited SUV39H1 to suppress miR-149-5p transcription, in turn activating Wnt/ß-catenin pathway, and forming a positive feedback loop with FOXM1. PTOV1-AS1 inhibits miR-149-5p by a positive feedback loop with FOXM1-mediated Wnt/ß-catenin pathway, which provides insights into a potential novel target for enhancing the effectiveness of chemotherapy in colorectal cancer patients.

Salivary Protein Cyclin-Dependent Kinase-like from Grain Aphid Sitobion avenae Suppresses Wheat Defense Response and Enhances Aphid Adaptation.

Aphids are insect pests that suck phloem sap and introduce salivary proteins into plant tissues through saliva secretion. The effector of salivary proteins plays a key role in the modulation of host plant defense responses and enhancing aphid host adaptation. Based on previous transcriptome sequencing results, a candidate effector cyclin-dependent kinase-like (CDK) was identified from the grain aphid Sitobion avenae. In this study, the function of SaCDK in wheat defense response and the adaptation of S. avenae was investigated. Our results showed that the transient overexpression of SaCDK in tobacco Nicotiana benthamiana suppressed cell death triggered by mouse pro-apoptotic protein-BAX or Phytophthora infestans PAMP-INF1. SaCDK, delivered into wheat cells through a Pseudomonas fluorescens-mediated bacterial type III secretion system, suppressed callose deposition in wheat seedlings, and the overexpression of SaCDK in wheat significantly decreased the expression levels of salicylic acid and jasmonic acid signaling pathway-related genes phenylalanine ammonia lyase (PAL), pathogenesis-related 1 protein (PR1), lipoxygenase (LOX) and Ω-3 fatty acid desaturase (FAD). In addition, aphid bioassay results showed that the survival and fecundity of S. avenae were significantly increased while feeding on the wheat plants carrying SaCDK. Taken together, our findings demonstrate that the salivary protein SaCDK is involved in inhibiting host defense response and improving its host adaptation, which lays the foundation to uncover the mechanism of the interaction of cereal aphids and host plants.

SmCSP4 from aphid saliva stimulates salicylic acid-mediated defence responses in wheat by interacting with transcription factor TaWKRY76.

Aphid salivary proteins are critical in modulating plant defence responses. Grain aphid Sitobion miscanthi is an important wheat pest worldwide. However, the molecular basis for the regulation of the plant resistance to cereal aphids remains largely unknown. Here, we show that SmCSP4, a chemosensory protein from S. miscanthi saliva, is secreted into wheat plants during aphid feeding. Delivery of SmCSP4 into wheat leaves activates salicylic acid (SA)-mediated plant defence responses and subsequently reduces aphid performance by deterring aphid feeding behaviour. In contrast, silencing SmCSP4 gene via nanocarrier-mediated RNAi significantly decreases the ability of aphids to activate SA defence pathway. Protein-protein interaction assays showed that SmCSP4 directly interacts with wheat transcriptional factor TaWRKY76 in plant nucleus. Furthermore, TaWRKY76 directly binds to the promoter of SA degradation gene Downy Mildew Resistant 6 (DMR6) and regulates its gene expression as transcriptional activator. SmCSP4 secreted by aphids reduces the transcriptional activation activity of TaWRKY76 on DMR6 gene expression, which is proposed to result in increases of SA accumulation and enhanced plant immunity. This study demonstrated that SmCSP4 acts as salivary elicitor that is involved in activating SA signalling defence pathway of wheat by interacting with TaWRKY76, which provide novel insights into aphid-cereal crops interactions and the molecular mechanism on induced plant immunity.

Association of neutrophil to lymphocyte ratio and D-dimer with functional outcome in patients with cerebral venous sinus thrombosis.

BACKGROUND: Investigations on the risk factors for the prognosis of cerebral venous sinus thrombosis (CVST) are limited. This study aimed to explore whether specific inflammatory factors and coagulation indictors are associated with functional outcome in patients treated for CVST. METHODS: This retrospective study included 137 patients admitted to our hospital between January 2010 and October 2021. The functional outcome was assessed with the modified Rankin Scale (mRS) score at discharge. Patients were divided into two groups, 102 patients with favorable outcomes (mRS 0-1) and 35 patients with poor outcomes (mRS 2-6). The clinical indexes were compared between two groups. Multivariable logistic regression was performed to identify the independent influencing factors for poor outcomes of CVST patients. The prognostic indicators were analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Compared with the favorable outcome group, the incidence of impaired consciousness and brain lesion, the levels of D-dimer, RDW, neutrophil count, neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width to platelet ratio (%) on admission were significantly higher in the poor outcome group, while the level of lymphocyte count was significantly lower. After multivariable logistic regression analysis, baseline D-dimer level (odds ratio (OR), 1.180; 95% confidence interval (CI), 1.019-1.366, P = 0.027) and NLR (OR, 1.903; 95%CI, 1.232-2.938, P = 0.004) were significantly associated with unfavorable outcome at discharge. The ROC curve analysis showed that the areas under the curve of D-dimer, NLR and their combined detection for predicting worse outcome were 0.719, 0.707 and 0.786, respectively. CONCLUSIONS: Elevated D-dimer level and NLR on admission were associated with an increased risk of poor functional outcome in patients with CVST.

The salivary effector protein Sg2204 in the greenbug Schizaphis graminum suppresses wheat defence and is essential for enabling aphid feeding on host plants.

Aphids secrete diverse repertoires of salivary effectors into host plant cells to promote infestation by modulating plant defence. The greenbug Schizaphis graminum is an important cereal aphid worldwide. However, the secreted effectors of S. graminum are still uncharacterized. Here, 76 salivary proteins were identified from the watery saliva of S. graminum using transcriptome and proteome analyses. Among them, a putative salivary effector Sg2204 was significantly up-regulated during aphid feeding stages, and transient overexpression of Sg2204 in Nicotiana benthamiana inhibited cell death induced by BAX or INF1. Delivering Sg2204 into wheat via the type III secretion system of Pseudomonas fluorescens EtAnH suppressed pattern-triggered immunity (PTI)-associated callose deposition. The transcript levels of jasmonic acid (JA)- and salicylic acid (SA)-associated defence genes of wheat were significantly down-regulated, and the contents of both JA and SA were also significantly decreased after delivery of Sg2204 into wheat leaves. Additionally, feeding on wheat expressing Sg2204 significantly increased the weight and fecundity of S. graminum and promoted aphid phloem feeding. Sg2204 was efficiently silenced via spray-based application of the nanocarrier-mediated transdermal dsRNA delivery system. Moreover, Sg2204-silenced aphids induced a stronger wheat defence response and resulted in negative impacts on aphid feeding behaviour, survival and fecundity. Silencing of Sg2204 homologues from four aphid species using nanocarrier-delivered dsRNA also significantly reduced aphid performance on host plants. Thus, our study characterized the salivary effector Sg2204 of S. graminum involved in promoting host susceptibility by suppressing wheat defence, which can also be regarded as a promising RNAi target for aphid control.

Salivary Effector Sm9723 of Grain Aphid Sitobion miscanthi Suppresses Plant Defense and Is Essential for Aphid Survival on Wheat.

Aphid salivary effectors play important roles in modulating plant defense responses. The grain aphid Sitobion miscanthi is one of the most economically important cereal aphids worldwide. However, little information is available on the identification and functional analysis of salivary effectors of S. miscanthi. In this study, a candidate salivary effector Sm9723 was identified, which was specifically expressed in aphid salivary glands and highly induced during the aphid feeding phase. Transient overexpression of Sm9723 in Nicotiana benthamiana suppressed BAX and INF1-induced cell death. Further, Sm9723 overexpression inhibited N. benthamiana defense responses by reducing pattern-triggered immunity associated callose deposition and expression levels of jasmonic and salicylic acid-associated defense genes. In addition, the salivary effector Sm9723 of S. miscanthi was effectively silenced through nanocarrier-mediated dsRNA delivery system. After silencing Sm9723, fecundity and survival of S. miscanthi decreased significantly, and the aphid feeding behavior was also negatively affected. These results suggest salivary effector Sm9723 is involved in suppressing plant immunity and is essential in enabling aphid virulence, which could be applied as potential target gene for RNAi-mediated pest control of S. miscanthi.

Anti-neuron antibody syndrome: clinical features, cytokines/chemokines and predictors.

BACKGROUND: Neuroimmunology is a rapidly expanding field, and there have been recent discoveries of new antibodies and neurological syndromes. Most of the current clinical studies have focused on disorders involving one specific antibody. We have summarized a class of antibodies that target common neuronal epitopes, and we have proposed the term "anti-neuron antibody syndrome" (ANAS). In this study, we aimed to clarify the clinical range and analyse the clinical features, cytokines/chemokines and predictors in ANAS. METHODS: This was a retrospective cohort study investigating patients with neurological manifestations that were positive for anti-neuron antibodies. RESULTS: A total of 110 patients were identified, of which 43 patients were classified as having autoimmune encephalitis (AE) and the other 67 were classified as having paraneoplastic neurological syndrome (PNS). With regards to anti-neuron antibodies, 42 patients tested positive for anti-N-methyl-D-aspartate receptor (NMDAR) antibody, 19 for anti-Hu, 14 for anti-Yo and 12 for anti-PNMA2 (Ma2). There were significant differences between the ANAS and control groups in serum B cell-activating factor (BAFF) levels and in cerebrospinal fluid (CSF) C-X-C motif chemokine10 (CXCL10), CXCL13, interleukin10 (IL10), BAFF and transforming growth factor ß1 (TGFß1) levels. Predictors of poor outcomes included having tumours (P = 0.0193) and having a chronic onset (P = 0.0306), and predictors of relapses included having lower levels of CSF BAFF (P = 0.0491) and having a larger ratio of serum TGFß1/serum CXCL13 (P = 0.0182). CONCLUSIONS: Most patients with ANAS had a relatively good prognosis. Having tumours and a chronic onset were both associated with poor outcomes. CSF BAFF and the ratio of serum TGFß1/serum CXCL13 were associated with relapses.

Human cytomegalovirus inhibits the proliferation and invasion of extravillous cytotrophoblasts via Hippo-YAP pathway.

BACKGROUND: Human cytomegalovirus (HCMV) infection in utero is very common during pregnancy, which can lead to adverse outcomes in both pregnancy and progeny, but its pathogenesis has not been fully clarified. The decrease of extravillous cytotrophoblasts (EVT) invasion is an essential pathophysiological process of some pregnancy complications. Hippo-YAP signaling pathway plays an important role in regulating cell proliferation and apoptosis. However, whether YAP is involved in HCMV uterine infection remains to be studied. METHODS: The primary EVT was cultured and infected by the HCMV strain AD169 virus in vitro. Immunofluorescence staining of HCMVpp65 antigen was conducted afterward to confirm the establishment of an infection model. The optimal virus infection dose was determined by the EVT proliferation status in vitro. Real-time PCR was performed to examine the mRNA level of major genes involved in the Hippo pathway in EVT after HCMV infection. The effect of HCMV on the expression of YAP protein in EVT was evaluated by Immunofluorescence staining and Western blot. An in vitro cell invasion assay was carried out to analyze the influence of HCMV on EVT invasion. The changes of EVT invasion was accessed by establishing YAP silencing and over-expression models using YAP1 specific siRNA and plasmid pcDH. RESULTS: The optimal HCMV infection dose was 282.5TCID50/ml. Compared to the control group, the infection of HCMV significantly reduced the mRNA expression of Mst1, Mst2, SAV, Lats1, Lats2, Mob1, YAP1, TAZ, TEAD1-4 genes and YAP protein expression in the Hippo-YAP pathway. HCMV infection also decreased the EVT invasion. In non-infected EVT, the number of transmembrane EVT cells was significantly reduced when YAP1 gene was silenced, while it was significantly increased when YAP1 gene was over-expressed. In the HCMV-infected EVT, the number of transmembrane EVT cells significantly increased when over-expressed and eventually recovered to the level of NC. CONCLUSIONS: HCMV may decrease EVT invasion by inhibiting the expression of mRNA and protein of YAP in the Hippo-YAP signaling pathway. HCMV eventually reduces the invasion ability of EVT by inhibiting multiple genes in the Hippo-YAP signaling pathway, especially inhibiting YAP which serves as the downstream effector.

Insight into watery saliva proteomes of the grain aphid, Sitobion avenae.

The grain aphid, Sitobion avenae, is an economically important cereal pest worldwide. Aphid saliva plays an essential role in the interaction between aphids and their host plants. However, limited information is available regarding the proteins found in the saliva of S. avenae. Here, the watery saliva proteins from S. avenae were collected in an artificial diet and identified using a liquid chromatography-mass spectrometry/mass spectrometry analysis. A total of 114 proteins were identified in S. avenae saliva, including several enzymes, binding proteins, and putative effectors, as well as other proteins with unknown functions. In comparison with salivary proteins from nine other aphid species, the most striking feature of the salivary protein from S. avenae was the different patterns of protein functions. Several orthologous proteins secreted by other aphid species such as glucose dehydrogenase, elongation factors, and effector C002 were also detected in S. avenae saliva and speculated to play a significant role in aphid-plant interactions. These results provide further insight into the molecular basis between aphids and cereal plant interactions.

Transcriptome analysis reveals rapid defence responses in wheat induced by phytotoxic aphid Schizaphis graminum feeding.

BACKGROUND: Schizaphis graminum is one of the most important and devastating cereal aphids worldwide, and its feeding can cause chlorosis and necrosis in wheat. However, little information is available on the wheat defence responses triggered by S. graminum feeding at the molecular level. RESULTS: Here, we collected and analysed transcriptome sequencing data from leaf tissues of wheat infested with S. graminum at 2, 6, 12, 24 and 48 hpi (hours post infestation). A total of 44,835 genes were either up- or downregulated and differed significantly in response to aphid feeding. The expression levels of a number of genes (9761 genes) were significantly altered within 2 hpi and continued to change during the entire 48 h experiment. Gene Ontology analysis showed that the downregulated DEGs were mainly enriched in photosynthesis and light harvesting, and the total chlorophyll content in wheat leaves was also significantly reduced after S. graminum infestation at 24 and 48 hpi. However, a number of related genes of the salicylic acid (SA)-mediated defence signalling pathway and MAPK-WRKY pathway were significantly upregulated at early feeding time points (2 and 6 hpi). In addition, the gene expression and activity of antioxidant enzymes, such as peroxidase and superoxide dismutase, were rapidly increased at 2, 6 and 12 hpi. DAB staining results showed that S. graminum feeding induced hydrogen peroxide (H2O2) accumulation at the feeding sites at 2 hpi, and increased H2O2 production was detected with the increases in aphid feeding time. Pretreatment with diphenylene iodonium, an NADPH oxidase inhibitor, repressed the H2O2 accumulation and expression levels of SA-associated defence genes in wheat. CONCLUSIONS: Our transcriptomic analysis revealed that defence-related pathways and oxidative stress in wheat were rapidly induced within hours after the initiation of aphid feeding. Additionally, NADPH oxidase plays an important role in aphid-induced defence responses and H2O2 accumulation in wheat. These results provide valuable insight into the dynamic transcriptomic responses of wheat leaves to phytotoxic aphid feeding and the molecular mechanisms of aphid-plant interactions.

MicroRNA-149 Increases the Sensitivity of Colorectal Cancer Cells to 5-Fluorouracil by Targeting Forkhead Box Transcription Factor FOXM1.

BACKGROUND/AIMS: Previously, we have shown that microRNA (miR)-149 suppresses the migration and invasion of colorectal cancer (CRC) cells by targeting forkhead box transcription factor (FOXM1). However, the roles of miR-149 in the chemoresistance of CRC cells to 5-Fluorouracil (5-FU) is unclear. The aim of this study is to investigate whether miR-149 targets FOXM1 to regulate the 5-FU resistance of CRC. METHODS: The qRT-PCR assay was performed to detect the expression of miR-149 in 5-FU-resistant CRC cells (HCT-8/5-FU and LoVo/5-FU) and their parental CRC cells (HCT-8 and LoVo). Also, the effects of miR-149 expression on the sensitivity of CRC cells to 5-FU were determined by gain- and loss-of-function assays. Finally, whether miR-149 regulates the 5-FU resistance of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1) was investigated. RESULTS: The expression of miR-149 was significantly downregulated in 5-FU-resistant CRC cells in comparison with their parental CRC cells. Re-expression of miR-149 could enhance the 5-FU sensitivity of 5-FU-resistant CRC cells by increasing 5-FU-inducing apoptosis, while downregulation of miR-149 could decrease the 5-FU sensitivity of parental CRC cells by decreasing 5-FU-inducing apoptosis. In addition, the luciferase assay indicated that miR-149 could bind to the 3'-UTR sequence of FOXM1 mRNA. The silencing of FOXM1 could mimic the effect of miR-149 upregulation on the 5-FU resistance of 5-FU-resistant CRC cells. Furthermore, the expression of miR-149 in the 5-FU-responding CRC tissues was significantly higher than that in the non-responding tissues and inversely correlated with FOXM1 mRNA level. CONCLUSIONS: MiR-149 reverses the resistance of CRC cells to 5-FU by directly targeting FOXM1. Thus, targeting miR-149/FOXM1 signaling will be a potential strategy in the treatment of 5-FU-chemoresistant CRC.

MicroRNA-149 suppresses colorectal cancer cell migration and invasion by directly targeting forkhead box transcription factor FOXM1.

BACKGROUND/AIMS: The aim of this study is to investigate the clinicopathological and prognostic values of miR-149 expression and its roles in colorectal cancer (CRC) progression. METHODS: qRT-PCR was performed to detect miR-149 expression in CRC cell lines or tissues. Also, the clinical significance of miR-149 expression was investigated. The study further explored whether miR-149 inhibits migration and invasion of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1). RESULTS: miR-149 was significantly downregulated in CRC tissues, and low miR-149 expression was observed to be significantly correlated with lymph node or distant metastasis and advanced TNM stage of CRC patients. Patients with low miR-149 expression showed poorer prognosis than those with high miR-149 expression, and multivariate analyses indicated that status of miR-149 expression might be an independent prognostic factor. Gain- and loss - of - function assays indicated that miR-149 significantly inhibited growth, migration and invasion of CRC cells by targeting FOXM1. Furthermore, FOXM1 was significantly uiregulated in CRC tissues and inversely correlated with miR-149 expression. CONCLUSIONS: mR-149 was an independent prognostic factor and could inhibit migration and invasion of CRC cells, at least partially by targeting FOXM1.

Sarcoidosis detected after COVID­19 with T­SPOT.TB positive: A case report.

Sarcoidosis is an idiopathic multisystem disorder with unknown etiology. Due to clinical similarities among sarcoidosis, tuberculosis (TB) infection and malignant diseases (such as lymphoma, lung carcinoma and pituitary tumor), the diagnosis of sarcoidosis is challenging. The present report describes a case of sarcoidosis in a 48-year-old male with complaint of chest pain 1 month after Coronavirus disease 2019. The patient underwent whole-body 18F-fluorodeoxyglucose (18F-FDG) PET-CT imaging, which revealed multiple lymphadenopathies throughout the body without lung parenchyma involvement. Biochemical examinations such as T-SPOT.TB test and pathological examination of right supraclavicular lymph node revealed positive T-SPOT.TB but negative Ziehl-Neelsen staining. However, non-caseating epithelioid granulomas were observed in the mediastinal biopsy, indicating the diagnosis of sarcoidosis. The patient was clinically stable, and the symptom of chest pain was gradually relieved without any specific treatment. Outpatient follow-up continued every 3 months. The present case suggested a possible link between coronavirus infection and sarcoidosis, which suggests the advantages of 18F-FDG PET-CT for the detection of sarcoidosis. However, T-SPOT.TB is insufficient for differentiating between sarcoidosis and TB.

Toxicity of Cry- and Vip3Aa-Class Proteins and Their Interactions against Spodoptera frugiperda (Lepidoptera: Noctuidae).

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is one of the most important insect pests affecting corn crops worldwide. Although planting transgenic corn expressing Bacillus thuringiensis (Bt) toxins has been approved as being effective against FAW, its populations' resistance to Bt crops has emerged in different locations around the world. Therefore, it is important to understand the interaction between different Bt proteins, thereby delaying the development of resistance. In this study, we performed diet-overlay bioassays to evaluate the toxicity of Cry1Ab, Cry1Ac, Cry1B, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, Vip3Aa11, Vip3Aa19, and Vip3Aa20, as well as the interaction between Cry1Ab-, Cry1F-, Cry2Ab-, and Vip3Aa-class proteins against FAW. According to our results, the LC50 values of Bt proteins varied from 12.62 ng/cm2 to >9000 ng/cm2 (protein/diet), among which the Vip3Aa class had the best insecticidal effect. The combination of Cry1Ab and Vip3Aa11 exhibited additive effects at a 5:1 ratio. Cry1F and Vip3Aa11 combinations exhibited additive effects at 1:1, 1:2, and 5:1 ratios. The combination of Cry1F and Vip3Aa19 showed an antagonistic effect when the ratio was 1:1 and an additive effect when the ratio was 1:2, 2:1, 1:5, and 5:1. Additionally, the combinations of Cry1F and Vip3Aa20 showed antagonistic effects at 1:2 and 5:1 ratios and additive effects at 1:1 and 2:1 ratios. In addition to the above combinations, which had additive or antagonistic effects, other combinations exhibited synergistic effects, with variations in synergistic factors (SFs). These results can be applied to the establishment of new pyramided transgenic crops with suitable candidates, providing a basis for FAW control and resistance management strategies.

miR-101-3p-mediated role of PDZK1 in hepatocellular carcinoma progression and the underlying PI3K/Akt signaling mechanism.

BACKGROUND: The molecular targets and associated mechanisms of hepatocellular carcinoma (HCC) have been widely studied, but the roles of PDZK1 in HCC are unclear. Therefore, the aim of this study is to explore the role and associated mechanisms of PDZK1 in HCC. RESULTS: It was found that the expression of PDZK1 in HCC tissues was higher than that in paired paracancerous tissues. High expression of PDZK1 was associated with lymph node metastasis, degree of differentiation, and clinical stage. Upregulation of PDZK1 in HCC cells affected their proliferation, migration, invasion, apoptosis, and cell cycle, and also induced PI3K/AKT activation. PDZK1 is a downstream target gene of miR-101-3p. Accordingly, increase in the expression of miR-101-3p reversed the promotive effect of PDZK1 in HCC. Moreover, PDZK1 was found to accelerate cell proliferation and promote the malignant progression of HCC via the PI3K/AKT pathway. CONCLUSION: Our study indicated that the miR-101-3p/PDZK1 axis plays a role in HCC progression and could be beneficial as a novel biomarker and new therapeutic target for HCC treatment.

Chemotherapy-induced high expression of IL23A enhances efficacy of anti-PD-1 therapy in TNBC by co-activating the PI3K-AKT signaling pathway of CTLs.

Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.

Psychological Impact of COVID-19 Lockdown and Its Evolution: A Case Study Based on Internet Searching Data during the Lockdown of Wuhan 2020 and Shanghai 2022.

It has been three years since the initial outbreak of COVID-19 in Wuhan, China, which incurred huge damage both physically and psychologically on human's normal life. As a prevention measure, the lockdown was first adopted by Wuhan, then by a long list of Chinese cities and many other major cities around the world. Lockdown is the most restrictive social distancing strategy, turning out effective in mitigating the spreading of COVID-19 on the community level, which, however, cuts off all social interactions and isolates healthy people from each other. The isolated nature of the lockdown could induce severe mental health issues, forming one major source of depression and domestic violence. Given the potential side effect, a comprehensive investigation based on reliable data sources is needed to evaluate the real psychological impact of COVID-19 lockdown and its evolution over time, particularly in the time when the Omicron variant, known for its low death risk, dominates the pandemic. Based on the Baidu Searching Index data collected for Wuhan and Shanghai, two major cities in China that suffered from long-lasting (over two months) lockdowns in 2020 and 2022, respectively, it is found that the major psychological issue during the lockdown period is not induced by the spreading of COVID-19, but by the execution of lockdown. With the deepening of knowledge about COVID-19 and the decrease in the death risk, the psychological impact of lockdown keeps increasing, while the impact of virus spreading becomes less important and even irrelevant to depression and domestic violence issues. The findings reveal that from the psychological perspective, the negative effect of lockdown already overweighs the positive one, which is especially true for the Omicron variant provided its almost ignorable death risk. Therefore, it is necessary to re-evaluate the yield and cost of lockdown for those countries where the COVID-19 pandemic has not yet come to an end.

Two salivary proteins Sm10 and SmC002 from grain aphid Sitobion miscanthi modulate wheat defense and enhance aphid performance.

The grain aphid Sitobion miscanthi is a serious pest of wheat that causes severe economic damage by sucking phloem sap and transmitting plant viruses. Here, two putative salivary effector homologs from S. miscanthi (Sm10 and SmC002) were selected based on sequence similarity to other characterized aphid candidate effectors. These effectors were then delivered into wheat cells separately via the type III secretion system of Pseudomonas fluorescens to elucidate their functions in the regulation of plant defenses and host fitness. The results showed that the delivery of either Sm10 or SmC002 into wheat plants significantly suppressed callose deposition and affected the transcript levels of callose synthase genes. The expression levels of salicylic acid (SA)-associated defense genes were upregulated significantly in wheat leaves carrying either Sm10 or SmC002. Moreover, LC-MS/MS analysis revealed that wheat SA levels significantly increased after the delivery of the two effectors. The results of aphid bioassays conducted on the wheat plants carrying Sm10 or SmC002 showed significant increases in the survival and fecundity of S. miscanthi. This study demonstrated that the Sm10 and SmC002 salivary effectors of S. miscanthi enhanced host plant susceptibility and benefited S. miscanthi performance by regulating wheat defense signaling pathways.

Secondary symbionts affect aphid fitness and the titer of primary symbiont.

Bacterial symbionts associated with aphids are important for their ecological fitness. The corn leaf aphid, Rhopalosiphum maidis (Fitch), is one of the most damaging aphid pests on maize and has been reported to harbor Hamiltonella defensa and Regiella insecticola while the effects of the secondary symbionts (S-symbionts) on host ecology and primary symbiont Buchnera aphidicola remain unclear. Here, four aphid strains were established, two of which were collected from Langfang - Hebei Province, China, with similar symbiont pattern except for the presence of H. defensa. Two other aphid strains were collected from Nanning - Guangxi Province, China, with the same symbiont infection except for the presence of R. insecticola. Phylogenetic analysis and aphid genotyping indicated that the S-symbiont-infected and free aphid strains from the same location had identical genetic backgrounds. Aphid fitness measurement showed that aphid strain infected with H. defensa performed shortened developmental duration for 1st instar and total nymph stages, reduced aphid survival rate, offspring, and longevity. While the developmental duration of H-infected strains was accelerated, and the adult weight was significantly higher compared to the H-free strain. Infection with R. insecticola did not affect the aphid's entire nymph stage duration and survival rate. As the H-strain does, aphids infected with R. insecticola also underwent a drop in offspring, along with marginally lower longevity. Unlike the H-infected strain, the R-infected strain performed delayed developmental duration and lower adult weight. The B. aphidicola titers of the H-infected strains showed a steep drop during the aphid 1st to 3rd instar stages, while the augmentation of B. aphidicola titers was found in the R-infected strain during the aphid 1st to 3rd instar. Our study investigated for the first time the effect of the S-symbionts on the ecology fitness and primary symbiont in R. maidis, indicating that infection with secondary symbionts leads to the modulation of aphid primary symbiont abundance, together inducing significant fitness costs on aphids with further impact on environmental adaptation and trophic interactions.

Sulfur enhancement effects for uranium bioleaching in column reactors from a refractory uranium ore.

The feasibility of sulfur enhancement for uranium bioleaching in column reactors was assessed with a designed mixed Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans and Leptospirillum ferriphilum from a refractory uranium ore. The uranium extraction reached 86.2% with the sulfur enhancement (1 g/kg) in 77 days leaching process, increased by 12.6% vs. the control without sulfur addition. The kinetic analysis showed that uranium bioleaching with sulfur enhancement in columns followed an internal diffusion through the product layer-controlled model. Ore residue characteristics indicated that sulfur enhancement could strengthen the porosity of passivation layer, improving the ore permeability. Notably, bacterial community analysis showed that sulfur enhancement at 1 g/kg could make the iron-oxidizing and sulfur-oxidizing bacteria on the ore surface maintain a good balance (approx. 1:1), and thus decomposing ore more effectively. Lastly, a possible mechanism model for uranium bioleaching with sulfur enhancement was proposed.