A Combination of CPI-0610 and SAHA Induces Apoptosis through STAT3 and p38 Signalling Pathways in Diffuse Large B-cell Lymphoma Cells.

BACKGROUND: Although immunotherapies have greatly improved diffuse large B-cell lymphoma (DLBCL) prognosis, a proportion of patients remain to be relapsed or refractory. Therefore, the identification of novel therapeutic targets and drugs is urgently required. Inhibition of the bromodomain and extra-terminal (BET) proteins has been a promising therapeutic strategy for various haematologic cancers. CPI-0610 is a potent and selective BET inhibitor. The effects of CPI-0610 in DLBCL cells have not been reported yet. AIMS: The aim of this study was to assess the effects of CPI-0610 in DLBCL and its underlying mechanisms. METHODS: DLBCL cells were treated with CPI-0610, followed by measuring cell viability, cell cycle, apoptosis, autophagy, and specific cell signaling pathways. Moreover, immunodeficient mice were engrafted with SUDHL2 cells and then treated with CPI-0610 for analysis of tumor burden. We also analyzed the synergistic effect of CPI-0610 with histone deacetylase inhibitor suberoylanilide hydroxamic acid. RESULTS: The present study demonstrated that CPI-0610 displayed cell cytotoxicity by arresting the G1 cell cycle and inducing endogenous and exogenous apoptotic pathways. Additionally, CPI-0610 decreased BRD4 and c-Myc expressions and affected MAPK, JAK/STAT, and AKT signalling pathways in human DLBCL cells. An in vivo experiment exhibited that CPI-0610 decreased the primary tumour growth of the DLBCL xenograft model. Furthermore, the use of CPI-0610 in combination with suberoylanilide hydroxamic acid exhibited a specific synergistic effect in inducing apoptosis through the regulation of STAT3 and p38. CONCLUSION: Targeting BET may be an effective therapeutic strategy and potentiated by a combination with histone deacetylase inhibition in DLBCL.

Chidamide Induces Epstein-Barr Virus (EBV) Lytic Infection and Acts Synergistically with Tenofovir to Eliminate EBV-Positive Burkitt Lymphoma.

Epstein-Barr virus (EBV) is a type of human γ-herpesvirus, and its reactivation plays an important role in the development of EBV-driven Burkitt lymphoma (BL). Despite intensive chemotherapy, the prognosis of relapsed/refractory BL patients remains unfavorable, and a definitive method to completely eliminate latent EBV infection is lacking. Previous studies have demonstrated that histone deacetylase (HDAC) inhibitors can induce the transition of EBV from latency to the lytic phase. The lytic activation of EBV can be inhibited by tenofovir, a potent inhibitor of DNA replication. Herein, we explored the antitumor effect and EBV clearance potential of a novel HDAC inhibitor called chidamide, combined with tenofovir, in the treatment of EBV-positive BL. In the study, chidamide exhibited inhibitory activity against HDAC. Moreover, chidamide inhibited BL cell proliferation, arrested cell cycle progression, and induced BL cell apoptosis primarily by regulating the MAPK pathways. Additionally, chidamide promoted the transcription of lytic genes, including BZLF1, BMRF1, and BMLF1 Compared with chidamide alone, the addition of tenofovir further induced growth arrest and apoptosis in EBV-positive BL cells and inhibited the transcriptions of EBV lytic genes induced by chidamide alone. Furthermore, our in vivo data demonstrated that the combination of chidamide and tenofovir had superior tumor-suppressive effects in a mouse model of BL cell tumors. The aforementioned findings confirm the synergistic effect of chidamide combined with tenofovir in inducing growth inhibition and apoptosis in EBV-positive BL cells and provide an effective strategy for eliminating EBV and EBV-associated malignancies. SIGNIFICANCE STATEMENT: High levels of Epstein-Barr virus (EBV)-DNA have consistently been associated with unfavorable progression-free survival and overall survival in EBV-associated lymphomas. Therefore, identifying novel strategies to effectively eradicate tumor cells and eliminate EBV is crucial for lymphoma patients. This study confirmed, for the first time, the synergistic effect of chidamide combined with tenofovir in the treatment of Burkitt lymphoma and the eradication of EBV virus.

Associations among risk perception, health efficacy, and health behaviors for cardiovascular disease: an application of risk perception attitude framework.

Background: There is currently a pervasive prevalence of cardiovascular disease (CVD) risk worldwide and an inadequate amount of action is being taken to promote healthy lifestyle habits. The risk perception attitude (RPA) framework, which classifies individuals based on their risk perception and efficacy belief, enables us to predict their preventive behaviors. We applied the RPA framework to analyze CVD prevention behaviors among Chinese adults and extended its application to CVD objective risk. Methods: A cross-sectional survey was performed in two sites in Zhejiang Province, from March to August 2022, which contained self-reported CVD risk perception, objective CVD risk, efficacy belief, physical activity, healthy diet, and covariates. We used the RPA framework to categorize participants into four groups, then analysis was conducted to estimate inter-group differences in healthy behaviors. We further conducted a hierarchical logistic regression analysis with individuals' health behaviors as the dependent variable, using three blocks of independent variables. Results: Among 739 participants, healthy physical activity and healthy diet had significant differences among four RPA groups, post hoc tests clarified that the proportion of respondents with healthy PA in the responsive group (61.6%) was significantly higher than that in the other three groups. Risk perception and efficacy belief significantly predicted health behavior against CVD; the relationship between absolute CVD risk and health behavior was moderated by efficacy belief. Conclusions: Early CVD risk screening is crucial, but tailored support and a proper understanding of personal risk are essential to promote healthy behaviors. Developing communication and behavioral counseling intervention strategies on the basis of the RPA framework has the potential to promote healthy behaviors for CVD prevention.

Thymosin ß4 Exerts a Cytoprotective Function and Attenuates Liver Injury in Murine Hepatic Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation.

Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening complication that may occur after hematopoietic stem cell transplantation (HSCT). Hepatic sinusoidal endothelial cell (HSEC) injury and liver fibrosis are key mechanisms of HSOS. Thymosin ß4 (Tß4) is an active polypeptide that functions in a variety of pathologic and physiologic states, including inflammation regulation, anti-apoptosis, and anti-fibrosis. In this study, we found that Tß4 can stimulate HSEC proliferation, migration, and tube formation in vitro via activation of pro-survival signaling AKT (protein kinase B). In addition, Tß4 resisted γ irradiation-induced HSEC growth arrest and apoptosis in parallel with upregulation of anti-apoptotic protein B cell lymphoma extra-large (Bcl-xL) and B cell lymphoma-2 (Bcl-2), which may be associated with activation of AKT. More importantly, Tß4 significantly inhibited irradiation-induced pro-inflammatory cytokines in parallel with negative regulation of TLR4/MyD88/NF-κB and MAPK p38. Meanwhile, Tß4 reduced intracellular reactive oxygen species production and upregulated antioxidants in HSECs. Additionally, Tß4 inhibited irradiation-induced activation of hepatic stellate cells by downregulating the expression of fibrogenic markers α-SMA, PAI-1, and TGF-ß. In a murine HSOS model, levels of circulating alanine aminotransferase, aspartate aminotransferase, total bilirubin, and pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α were significantly reduced after administration of Tß4 peptide; furthermore, Tß4 treatment successfully ameliorated HSEC injury, inflammatory damage, and fibrosis of the murine liver. Taken together, our findings indicate that Tß4 stimulates proliferation and angiogenesis of HSECs, exerts a cytoprotective effect, and attenuates liver injury in a murine HSOS model, suggesting that its use may be a potential strategy to prevent and treat HSOS after HSCT.

Engineering of Oxidized Line Defects on CVD-Grown MoS2 Flakes.

Defect engineering is a promising means to create patterns on two-dimensional (2D) materials to enable unconventional properties. However, defects usually exist abundantly and randomly on 2D materials, which makes it difficult to tune the properties in a controllable manner. Therefore, it is highly desirable to find out the formation mechanism and controllable fabrication method of defects on 2D materials. In this report, we systematically investigated the line defects on monolayer MoS2 formed by introducing oxygen during the CVD growth. The line defects were formed due to the overoxidation of the MoS2 flake along crystal boundaries, which bulged out of the surface and had the same surface potential as the basal plane. Therefore, the MoS2 flake with line defects maintained the optical and electrical integrity but exhibited distinct properties as compared to the pristine one. By controlling the oxygen concentration during CVD growth, the density of the line defects can be precisely controlled to implement controllable property tuning. Moreover, during the transfer process, the MoS2 flake was easily broken along the line defects, which increased the active sites to achieve enhanced hydrogen evolution reaction performance. This work is expected to inspire the development of patterned functional 2D materials by defect engineering.

Clinicopathologic Features and Genomic Signature of De Novo CD5 + Diffuse Large B-Cell Lymphoma : A Multicenter Collaborative Study.

De novo CD5 + diffuse large B-cell lymphoma (DLBCL) has poor survival in the era of immunochemotherapy. Accurate gene-based typing and prognostic stratification can enhance the development of effective individualized treatments. Therefore, we conducted a multicenter retrospective study to evaluate the clinicopathologic characteristics, genomic profiles, and prognostic parameters of 61 patients with CD5 + DLBCL and 60 patients with CD5 - DLBCL, with the goal of facilitating accurate prognostic stratification and potential individualized treatment strategies. Compared with patients with CD5 - DLBCL, older age, advanced stage, higher incidence of central nervous system involvement, and MYC/BCL-2 and p53 overexpression were more prevalent in CD5 + DLBCL. Most patients with CD5 + DLBCL had lymph nodes with non-germinal center B-cell-like or activated B-cell-like subtype according to immunohistochemistry or Lymph2Cx assay. Next-generation sequencing showed that the proportion of MCD subtype (based on the co-occurrence of MYD88 and CD79B mutations) in the CD5 + DLBCL cohort was higher than that in the CD5 - DLBCL cohort (54.2% vs. 13.0%, P =0.005). Compared with the CD5 - cohort, CD5 + DLBCL patients showed poor 5-year overall survival (70.9% vs. 39.0%, P <0.001). Kaplan-Meier survival analysis indicated that cell of origin, MYC/BCL-2, p53, and BCL-6 expression did not have a prognostic impact on patients with CD5 + DLBCL. Multivariate analysis showed that age above 76 years, advanced stage, higher incidence of central nervous system involvement, and hypoalbuminemia were independent factors for poor prognosis in CD5 + DLBCL patients. In summary, CD5 + DLBCL displays poor prognosis, distinctive clinicopathologic characteristics and predominant genetic features of activated B-cell-like and MCD subtypes with worse survival outcome.

l-Asparaginase synergizes with etoposide via the PI3K/Akt/mTOR pathway in Epstein-Barr virus-positive Burkitt lymphoma.

Burkitt lymphoma (BL) is an aggressive Epstein-Barr virus (EBV)-driven B-cell lymphoma characterized by the translocation and rearrangement of the c-Myc proto-oncogene. High-intensity multidrug chemotherapy regimens have a limited effect on the survival of refractory or relapsed BL patients, mainly owing to the high EBV load and drug resistance. l-asparaginase ( l-Asp) and etoposide (VP-16) play a beneficial role in EBV-related lymphoproliferative diseases; however, their roles and mechanisms in BL remain unclear. In this study, we found that VP-16 inhibited BL cell proliferation and arrested the cell cycle at the G2 /M phase. It also induced autophagy and activated the extrinsic and intrinsic apoptotic signaling pathways in BL cells. Mechanistically, VP-16 inhibited c-Myc expression and regulated the PI3K/Akt/mTOR signaling pathway. Notably, VP-16 also showed a specific synergistic effect with l-Asp to induce apoptosis in EBV-positive BL cells but not in EBV-negative BL cells. VP-16 combined with l-Asp further inhibited c-Myc expression and downregulated the PI3K/Akt/mTOR signaling pathway. Additionally, we found that VP-16 inhibited the expression of latent membrane protein 1 (LMP1), and in combination with l-Asp further decreased LMP1 expression in Raji cells. Our in vivo data also showed that the dual-drug combination significantly inhibited the growth of BL tumors and prolonged the survival of mice compared to VP-16 alone. In conclusion, this study provides new evidence that l-Asp may enhance the antitumor effect of VP-16 by inhibiting the PI3K/Akt/mTOR signaling pathway in EBV-positive BL cells.

Application of the NU-1000 coated SPME fiber on analysis of trace organochlorine pesticides in water.

Herein, a novel solid-phase microextraction (SPME) fiber based on the NU-1000 sorbent was developed for direct immersion extraction of organochlorine pesticides (OCPs) in water samples. As a kind of metal-organic framework, the NU-1000 possessed the mesoporous channels which were beneficial for the mass transfer of target analytes. Extraction equilibrium was achieved rapidly with the optimal extraction time of 30 min. The NU-1000 coated fiber with a high specific surface area showed better extraction efficiencies than commercial fibers (65 µm PDMS/DVB or 85 µm PA) towards OCPs, with the enrichment factors of the NU-1000 coated fiber 2-20 times higher than the latter. NU-1000 coated fiber showed higher extraction efficiencies toward polycyclic aromatic hydrocarbons (PAHs) than OCPs and nitrobenzenes. This indicated that π-π interaction and CH-π interaction between pollutants and aromatic groups of the NU-1000 contributed to the high extraction efficiencies. Under the optimal conditions (extraction at 40 °C for 30 min and desorption at 260 °C for 6 min), the NU-1000 coated fiber coupled with gas chromatography-mass spectrometry (GC-MS) exhibited satisfied analytical performance on analysis of OCPs, with a wide linear range (0.1-2000 ng L-1), low limits of detections (LODs, 0.011-0.058 ng L-1), and good reproducibility and repeatability. The established method has been successfully applied to the determination of OCPs in surface water with good sensitivity and recoveries, which proved the great promise of the NU-1000 on the extraction of organic pollutants with conjugated groups.

A Novel Prognostic Index Model for Adult Hemophagocytic Lymphohistiocytosis: A Multicenter Retrospective Analysis in China.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Dielectric engineering enable to lateral anti-ambipolar MoTe2heterojunction.

Atomically two-dimensional (2D) materials have generated widespread interest for novel electronics and optoelectronics. Specially, owing to atomically thin 2D structure, the electronic bandgap of 2D semiconductors can be engineered by manipulating the surrounding dielectric environment. In this work, we develop an effective and controllable approach to manipulate dielectric properties of h-BN through gallium ions (Ga+) implantation for the first time. And the maximum surface potential difference between the intrinsic h-BN (h-BN) and the Ga+implanted h-BN (Ga+-h-BN) is up to 1.3 V, which is characterized by Kelvin probe force microscopy. More importantly, the MoTe2transistor stacked on Ga+-h-BN exhibits p-type dominated transfer characteristic, while the MoTe2transistor stacked on the intrinsic h-BN behaves as n-type, which enable to construct MoTe2heterojunction through dielectric engineering of h-BN. The dielectric engineering also provides good spatial selectivity and allows to build MoTe2heterojunction based on a single MoTe2flake. The developed MoTe2heterojunction shows stable anti-ambipolar behaviour. Furthermore, we preliminarily implemented a ternary inverter based on anti-ambipolar MoTe2heterojunction. Ga+implantation assisted dielectric engineering provides an effective and generic approach to modulate electric bandgap for a wide variety of 2D materials. And the implementation of ternary inverter based on anti-ambipolar transistor could lead to new energy-efficient logical circuit and system designs in semiconductors.

The Acetyltransferase KAT5 Inhibitor NU 9056 Promotes Apoptosis and Inhibits JAK2/STAT3 Pathway in Extranodal NK/T Cell Lymphoma.

BACKGROUND: Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive malignant non- Hodgkin's lymphoma (NHL) with a poor prognosis. Therefore, novel therapeutic biomarkers and agents must be identified for the same. KAT5 inhibitor, NU 9056, is a small molecule that can inhibit cellular proliferation; however, its role in ENKTL has not been studied. OBJECTIVE: The present study investigated the effect of NU 9056 in ENKTL cells and explored the possible molecular mechanism for its antitumour effect. METHODS: The role of NU 9056 in ENKTL cells was investigated through the Cell Counting Kit-8 assay, flow cytometry, Western blot, and real-time quantitative polymerase chain reaction assay. RESULTS: NU 9056 inhibited ENKTL cell proliferation and induced G2/M phase arrest. NU 9056 also induced apoptosis by upregulating DR4, DR5, and caspase 8 expressions. Additionally, NU 9056 increased the expression of Bax, Bid, and cytochrome C and decreased the expression of Bcl-2, Mcl-1, and XIAP. Furthermore, NU 9056 activated endoplasmic reticulum (ER) stress and inhibited the JAK2/STAT3 signalling pathway. The p38 mitogen-activated protein kinase (MAPK) signalling pathway was also activated by NU 9056, and the ERK signalling pathway was suppressed in natural killer/T cell lymphoma cells. CONCLUSION: NU 9056 inhibited cell proliferation, arrested cell cycle in the G2/M phase, and induced apoptosis through the stimulation of ER stress, thus inhibiting the JAK2/STAT3 signalling pathway and regulating MAPK pathways in ENKTL cells.

CARMA1 is required for Notch1-induced NF-κB activation in SIL-TAL1-negative T cell acute lymphoblastic leukemia.

The NF-κB signaling pathway is an important downstream pathway of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL) cells. However, the molecular mechanisms underlying the cascade activation of Notch1 in T-ALL cells are poorly understood. Here, we evaluated the role of CARMA1 in Notch1-induced NF-κB activation in T-ALL cells. CARMA1 was highly and specifically expressed in T-ALL cells and correlated with the prognosis of T-ALL patients. Interestingly, CARMA1 knockdown only inhibited the growth and proliferation of SIL-TAL1 fusion gene-negative T-ALL cells. In addition, CARMA1 knockdown arrested T-ALL cells at the G1 phase. Furthermore, CARMA1 knockdown significantly inhibited the proliferation of T-ALL cells in vivo and prolonged the survival of mice. Mechanistically, CARMA1 deficiency abolished Notch1-induced NF-κB transcriptional activation and significantly reduced expression levels of the NF-κB target genes c-Myc, Bcl-2, and CCR7. Taken together, these results of our study identify CARMA1 as one of the crucial mediators of Notch1-induced transformation of T-All cells, suggesting that CARMA1 is a promising therapeutic target for T-ALL due to its specific expression in lymphocytes. KEY MESSAGES: CARMA1 contributes to cell survival only in SIL-TAL1 negative T-ALL cells. CARMA1 is a crucial mediator of Notch1-induced activation of NF-κB pathway. CARMA1 is a promising therapeutic target for T-ALL.

Modulation of MoTe2/MoS2 van der Waals heterojunctions for multifunctional devices using N2O plasma with an opposite doping effect.

van der Waals layered heterojunctions have a variety of band offsets that open up possibilities for a wide range of novel and multifunctional devices. However, due to their poor pristine carrier concentrations and limited band modulation methods, multifunctional p-n heterojunctions are very difficult to achieve. In this report, we developed a highly effective N2O plasma process to treat MoTe2/MoS2 heterojunctions. This allowed us to adjust the hole and electron concentrations in the two materials independently and simultaneously. More importantly, for the first time, we were able to create opposite doping on the two sides of the junction through a single-step treatment. With a very wide doping range from pristine to degenerate levels, a MoTe2/MoS2 heterojunction can be modulated to behave as a forward rectifying diode with enhanced rectifying ratio and as a tunneling transistor with negative differential resistance at room temperature. The new approach provides an effective and generic doping scheme for heterojunctions to construct versatile and multifunctional electronic devices.

Risk stratification model based on VEGF and International Prognostic Index accurately identifies low-risk diffuse large B-cell lymphoma patients in the rituximab era.

Vascular endothelial growth factor affects the invasiveness of solid tumors by regulating angiogenesis. However, it is not clear whether VEGF could be used to predict the prognosis of DLBCL in the era of rituximab-based immunotherapy. We conducted a retrospective study to explore response to therapy and the prognostic value of VEGF on DLBCL in the rituximab era. The subjects were 65 patients with a histological diagnosis of DLBCL from the Affiliated Hospital of Xuzhou Medical University. Kaplan-Meier analysis was performed to estimate the cumulative survival rate of patients with different VEGF and IPI levels, and comparisons between groups were made using the log-rank test. DLBCL patients with elevated VEGF were more likely to have extranodal involvement, advanced stage, Myc/Bcl-2 double expression, and a higher Ki-67 score. Elevated VEGF was associated with poor therapeutic response and survival. When patients were divided into low, low-intermediate, high-intermediate and high-risk groups using the V-IPI model based on VEGF and IPI, PFS rates were 94.4, 74.1, 40.6 and 14.8%, respectively. This model better identified low-risk patients than IPI (85.9, 88.9, 37 and 7.8%). Our results demonstrate that VEGF predicts therapeutic response in DLBCL and the V-IPI model accurately predicts PFS of low-risk DLBCL in the rituximab era.

Prognostic Analysis of Patients with Primary Extranodal Lymphoma: A Retrospective Study.

BACKGROUND: Originating from extranodal organs or tissues, primary extranodal lymphoma (PENL) acts in different primary sites with diverse clinical performances and PENL has remarkable geographical differences and lacks the relevant reports in each region. PATIENTS AND METHODS: Two hundred and twenty PENL patients were enrolled, and the relevant clinical and laboratory indicators were analyzed. In addition, statistical methods were applied to analyze the effects of different factors on overall survival (OS) and progression-free survival (PFS) of patients. RESULTS: The three most frequent primary sites of PENL are the digestive system, head and neck, and central nervous system. The patients were classified into groups based on their risk status, resulting in low-risk, medium-low-risk, medium-high-risk, and high-risk, and their respective 3-year OS values were calculated, which showed that 121 patients (55%) were in the low-risk group and 3-year OS was 85.2% (25.9% medium-low-risk, 3-year OS 66.6%; 15% medium-high-risk, 3-year OS 61.9%; 4.09% high risk, 3-year OS 45.7%). A multivariate analysis of the Cox regression demonstrated that serum beta 2-microglobulin (ß2-MG) and lactate dehydrogenase (LDH) were independent prognostic factors for OS and PFS, respectively. Both the performance status and pathological subtypes were independent prognostic factors for OS and PFS. CONCLUSION: The correlated independent risk factors such as ß2-MG, LDH, performance status, and pathological subtypes, were helpful for effectively determining the prognosis of PENL patients and guiding treatment.

Epidemiological and clinical features in patients with coronavirus disease 2019 outside of Wuhan, China: Special focus in asymptomatic patients.

OBJECTIVES: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19. METHODS: Data on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed. RESULTS: In this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0-20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough. CONCLUSION: The symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.

Controllable Cell Deformation Using Acoustic Streaming for Membrane Permeability Modulation.

Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real-time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real-time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro- and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development.

EHMT2 inhibitor BIX-01294 induces endoplasmic reticulum stress mediated apoptosis and autophagy in diffuse large B-cell lymphoma cells.

Despite advancement in the treatment of diffuse large B-cell lymphoma (DLBCL), many patients tend to relapse or become refractory after initial therapy. Therefore, it is essential to identify novel therapeutic targets and drugs, understand the molecular pathogenesis mechanism of DLBCL, and find ways to prevent and treat relapsed or refractory DLBCL. BIX-01294 is a small molecule compound that specifically inhibits EHMT2 activity. In this study, we demonstrate that BIX-01294 triggered the inhibition of human DLBCL cell proliferation, lead to G1 phase arrest via increasing P21 level and reducing cyclin E level. BIX-01294 also induced apoptosis via endogenous and exogenous apoptotic pathways. Moreover, BIX-01294 triggered autophagy and activated ER stress in human DLBCL cells. Furthermore, we showed that both key components of ER stress, ATF3, and ATF4, are required for BIX-01294-induced apoptosis and autophagy. Hence, this study provides new evidence that EHMT2 may be a new therapeutic target, and BIX-01294 may be a potential therapeutic drug for treating DLBCL.

Splenic Diffuse Red Pulp Small B-Cell Lymphoma with Gastrointestinal Hemorrhage: A Case Report and Literature Review.

BACKGROUND: Splenic diffuse red pulp small B-cell lymphoma (SDRPSBCL) is rare and accounts for less than 1% of non-Hodgkin's lymphoma. As the first or accompanying symptoms of SDRPSBCL, gastrointestinal hemorrhage (GIH) is rather unusual. PATIENTS AND METHODS: We reported on a patient with SDRPSBCL complicated with GIH. According to the enteroscopy, pathological sections of spleen and intestine, immunohistochemistry and other related laboratory examinations, the patient was diagnosed as SDRPSBCL (stage IVb) complicated with colon and rectal ulcers. The clinical manifestations were hematochezia, unformed stool, continuous anal pain and poor quality of life. Subsequently, the patient was treated by six cycles of CHOP (cyclophosphamide + doxorubicin + vincristine + hydroprednisone) regimens. The clinical features, diagnosis and treatment were analyzed retrospectively and the relevant literatures were reviewed. RESULTS: After the first course of chemotherapy, the patient did not have any more bloody stool and the stool was shaped. After six cycles of chemotherapy, the patient's anus was no longer painful and he has been in complete remission according to the result of positron emission tomography CT. CONCLUSION: Through analysis of this case, we could elucidate that after the primary disease was alleviated, the bleeding degree of digestive tract was relieved, which provided the basis for the clinical treatment of this rare disease.

Headspace solid-phase microextraction of semi-volatile ultraviolet filters based on a superhydrophobic metal-organic framework stable in high-temperature steam.

Headspace solid-phase microextraction (HS-SPME) of low volatile analytes from complex aqueous samples can be substantially facilitated by elevating the temperature of the samples. However, many SPME coatings prepared from novel sorptive materials may suffer from low stabilities in hot water steam. Herein, a superhydrophobic metal-organic framework (MOF) derived from decorating the metal-oxo nodes of the amino-functionalized UiO-66(Zr) with phenylsilane was prepared and successfully developed into a novel SPME fiber coating. The highest extraction efficiencies towards the semi-volatile ultraviolet (UV) filters were achieved when the aqueous samples were heated up to 100 °C. It was notable that the lab-made coating exhibited extraordinary stability towards hot water steam, probably because the hydrophobic groups capped on the MOF prevented water molecules from entering and deconstructing its lattice. Even after being treated with water steam under 100 °C for 21 h, the extraction performance of the coating remained unchanged, and the crystal structure of the MOF maintained. Furthermore, a negligible matrix effect was observed even in the samples containing humic acid. Under the optimal extraction and thermal desorption conditions, a method for determining UV filters in aqueous samples was established, which possessed low detection limits (0.6-2.1 ng L-1), wide linear ranges (10-50000 ng L-1), good inter-fiber reproducibility (2.3-6.0%, n = 6), and satisfying intra-fiber repeatability (1.8-5.8%, n = 3). The method was successfully applied in quantifying UV filters in environmental water samples. In addition, the lab-made NH2-UiO-66(Zr)-shp-coated fiber was also suitable for the analysis of polycyclic aromatic hydrocarbons (PAHs). This study provided an effective strategy for preparing MOF coatings that can maintain their crystalline structures and high extraction performances in high-temperature steam.