When DNA damage responses meet tumor immunity: From mechanism to therapeutic opportunity.

DNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects. This review explores the mechanisms behind DNA damage-induced antitumor immune responses, the importance of DNA damage in antitumor immunity, and potential therapeutic approaches for cancer immunotherapy targeting DDR. Additionally, we discuss the challenges of combination therapy and strategies for integrating DNA damage-targeting therapies with current cancer immunotherapy. In summary, this review highlights the critical role of DNA damage in tumor immunology, underscoring the potential of DDR inhibitors as promising therapeutic modalities for cancer treatment.

Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice.

BACKGROUND: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively used to treat various human neoplasms. However, its clinical utility is hampered due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidative stress, DNA damage, and inflammatory responses. Nonetheless, the remedies for AIC are even not established. Therefore, we illustrate the role of NAD+/NADH modulation by NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action on AIC. METHODS AND RESULTS: AIC was established by intraperitoneal injection of ADR in C57BL/6 wild-type (WT) and NQO1 knockout (NQO1-/-) mice. All Mice were orally administered dunnione (named NQO1 substrate) before and after exposure to ADR. Cardiac biomarker levels in the plasma, cardiac dysfunction, oxidative biomarkers, and mRNA and protein levels of pro-inflammatory mediators were determined compared the cardiac toxicity of each experimental group. All biomarkers of Cardiac damage and oxidative stress, and mRNA levels of pro-inflammatory cytokines including cardiac dysfunction were increased in ADR-treated both WT and NQO1-/- mice. However, this increase was significantly reduced by dunnione in WT, but not in NQO1-/- mice. In addition, a decrease in SIRT1 activity due to a reduction in the NAD+/NADH ratio by PARP-1 hyperactivation was associated with AIC through increased nuclear factor (NF)-κB p65 and p53 acetylation in both WT and NQO1-/- mice. While an elevation in NAD+/NADH ratio via NQO1 enzymatic action using dunnione recovered SIRT1 activity and subsequently deacetylated NF-κB p65 and p53, however not in NQO1-/- mice, thereby attenuating AIC. CONCLUSION: Thus, modulation of NAD+/NADH by NQO1 may be a novel therapeutic approach to prevent chemotherapy-associated heart failure, including AIC.

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD(+) metabolism.

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD(+) in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD(+) levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage.

Pharmacological activation of NQO1 increases NAD⁺ levels and attenuates cisplatin-mediated acute kidney injury in mice.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD(+) is a cofactor for various enzymes associated with cellular homeostasis, we studied the effects of increased NAD(+) levels by means of NAD(P)H: quinone oxidoreductase 1 (NQO1) activation using a known pharmacological activator (ß-lapachone) in wild-type and NQO1(-/-) mice on cisplatin-induced renal dysfunction in vivo. The intracellular NAD(+)/NADH ratio in renal tissues was significantly increased in wild-type mice co-treated with cisplatin and ß-lapachone compared with the ratio in mice treated with cisplatin alone. Inflammatory cytokines and biochemical markers for renal damage were significantly attenuated by ß-lapachone co-treatment compared with those in the cisplatin alone group. Notably, the protective effects of ß-lapachone in wild-type mice were completely abrogated in NQO1(-/-) mice. Moreover, ß-lapachone enhanced the tumoricidal action of cisplatin in a xenograft tumor model. Thus, intracellular regulation of NAD(+) levels through NQO1 activation might be a promising therapeutic target for the protection of cisplatin-induced acute kidney injury.

Dissemination of clinical Escherichia coli strains harboring mcr-1, blaNDM-7 and siderophore-producing plasmids in a Chinese hospital.

BACKGROUND: Carbapenem-resistant E. coli (CREco) pose a significant public health threat due to their multidrug resistance. Colistin is often a last-resort treatment against CREco; however, the emergence of colistin resistance gene mcr-1 complicates treatment options. METHODS: Two E. coli strains (ECO20 and ECO21), recovered from hospitalized patients in distinct wards, exhibited resistance to carbapenems and colistin. Whole-genome sequencing and phenotypic characterization were employed to study resistance patterns, plasmid profiles, transferability of resistance and virulence genes, and siderophore production capabilities. Comparative genome analysis was used to investigate the genetic environment of mcr-1, blaNDM-7, and virulence clusters. RESULTS: Both E. coli strains exhibited thr presence of both mcr-1 and blaNDM-7 genes, showing high resistance to multiple antibiotics. Genomic analysis revealed the clonal transmission of these strains, possessing identical plasmid profiles (pMCR, pNDM, and pVir) associated with colistin resistance, carbapenem resistance, and virulence factors. Conjugation experiments confirmed the transferability of these plasmids, indicating their potential to disseminate resistance and virulence traits to other strains. Comparative genomic analyses unveiled the distribution of mcr-1 (IncX4-type) and blaNDM (IncX3-type) plasmids across diverse bacterial species, emphasizing their adaptability and threat. The novelty of pVir indicates its potential role in driving the evolution of highly adaptable and pathogenic strains. CONCLUSIONS: Our findings underscore the co-occurrence of mcr-1, blaNDM-7, and siderophore-producing plasmids in E. coli, which poses a significant concern for global health. This research is crucial to unravel the complex mechanisms governing plasmid transfer and recombination and to devise robust strategies to control their spread in healthcare settings.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Halopelagius longus sp. nov., a member of the family Halobacteriaceae isolated from a salt mine, and emended description of the genus Halopelagius.

A thermotolerant, extremely halophilic archaeon, BC12-B1(T), was isolated from a salt mine in Baicheng county, Xinjiang province, China. Colonies were off-white-grey. The cells stained Gram-negative, were motile and irregularly long-rod-shaped (variation in both width and length) with abundant gas vesicles. The strain was able to grow at 20-55 °C (optimum, 48 °C), at pH 6.0-8.0 (optimum, 7.0-7.3), with 1.8-6.0 M NaCl (optimum, 3.0-3.5 M) and with 0.02-2.2 M Mg(2+) (optimum, 0.1-0.2 M). Cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 8 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain BC12-B1(T) was most closely related to Halopelagius inordinatus RO5-2(T) (98.5 %) with less than 95 % sequence similarity to other described species. The genomic DNA G+C content of strain BC12-B1(T) was 64.0 mol%. The DNA-DNA hybridization value between strain BC12-B1(T) and Hpl. inordinatus RO5-2(T) was 43.6 %. The major polar lipids of strain BC12-B1(T) were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, four glycolipids and an unknown lipid. Based on phenotypic, chemotaxonomic and genotypic characteristics, strain BC12-B1(T) represents a novel species of the genus Halopelagius, for which the name Halopelagius longus sp. nov. is proposed. The type strain is BC12-B1(T) ( = CGMCC 1.12397(T) = JCM 18758(T)). An emended description of the genus Halopelagius is also provided.

Activation of lipopolysaccharide-TLR4 signaling accelerates the ototoxic potential of cisplatin in mice.

Dysfunction in immune surveillance during anticancer chemotherapy of patients often causes weakness of the host defense system and a subsequent increase in microbial infections. However, the deterioration of organ-specific function related to microbial challenges in cisplatin-treated patients has not yet been elucidated. In this study, we investigated cisplatin-induced TLR4 expression and its binding to LPS in mouse cochlear tissues and the effect of this interaction on hearing function. Cisplatin increased the transcriptional and translational expression of TLR4 in the cochlear tissues, organ of Corti explants, and HEI-OC1 cells. Furthermore, cisplatin increased the interaction between TLR4 and its microbial ligand LPS, thereby upregulating the production of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, via NF-κB activation. In C57BL/6 mice, the combined injection of cisplatin and LPS caused severe hearing impairment compared with that in the control, cisplatin-alone, or LPS-alone groups, whereas this hearing dysfunction was completely suppressed in both TLR4 mutant and knockout mice. These results suggest that hearing function can be easily damaged by increased TLR expression and microbial infections due to the weakened host defense systems of cancer patients receiving therapy comprising three to six cycles of cisplatin alone or cisplatin combined with other chemotherapeutic agents. Moreover, such damage can occur even though patients may not experience ototoxic levels of cumulative cisplatin concentration.

The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated. AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments. MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model. RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of ß-catenin, accelerating the cell cycle and promoting cell proliferation in vitro. CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/ß-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.

Identification of a Novel Gene Signature with DDR and EMT Difunctionalities for Predicting Prognosis, Immune Activity, and Drug Response in Breast Cancer.

Breast cancer, with an overall poor clinical prognosis, is one of the most heterogeneous cancers. DNA damage repair (DDR) and epithelial-mesenchymal transition (EMT) have been identified to be associated with cancer's progression. Our study aimed to explore whether genes with both functions play a more crucial role in the prognosis, immune, and therapy response of breast cancer patients. Based on the Cancer Genome Atlas (TCGA) cancer database, we used LASSO regression analysis to identify the six prognostic-related genes with both DDR and EMT functions, including TP63, YWHAZ, BRCA1, CCND2, YWHAG, and HIPK2. Based on the six genes, we defined the risk scores of the patients and reasonably analyzed the overall survival rate between the patients with the different risk scores. We found that overall survival in higher-risk-score patients was lower than in lower-risk-score patients. Subsequently, further GO and KEGG analyses for patients revealed that the levels of immune infiltration varied for patients with high and low risk scores, and the high-risk-score patients had lower immune infiltration's levels and were insensitive to treatment with chemotherapeutic agents. Furthermore, the Gene Expression Omnibus (GEO) database validated our findings. Our data suggest that TP63, YWHAZ, BRCA1, CCND2, YWHAG, and HIPK2 can be potential genetic markers of prognostic assessment, immune infiltration and chemotherapeutic drug sensitivity in breast cancer patients.

A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission.

BACKGROUND: Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. METHODS: We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). RESULTS: An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. CONCLUSIONS: Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.

miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis.

Radioresistance conferred by cancer stem cells (CSCs) is the principal cause of the failure of cancer radiotherapy. Eradication of CSCs is a prime therapeutic target and a requirement for effective radiotherapy. Three dimensional (3D) cell-cultured model could mimic the morphology of cells in vivo and induce CSC properties. Emerging evidence suggests that microRNAs (miRNAs) play crucial roles in the regulation of radiosensitivity in cancers. In this study, we aim to investigate the effects of miRNAs on the radiosensitivity of 3D cultured stem-like cells. Using miRNA microarray analysis in 2D and 3D cell culture models, we found that the expression of miR-29b-3p was downregulated in 3D cultured A549 and MCF7 cells compared with monolayer (2D) cells. Clinic data analysis from The Cancer Genome Atlas database exhibited that miR-29b-3p high expression showed significant advantages in lung adenocarcinoma and breast invasive carcinoma patients' prognosis. The subsequent experiments proved that miR-29b-3p overexpression decreased the radioresistance of cells in 3D culture and tumors in vivo through interfering kinetics process of DNA damage repair and inhibiting oncogenes RBL1, PIK3R1, AKT2, and Bcl-2. In addition, miR-29b-3p knockdown enhanced cancer cells invasion and migration capability. MiR-29b-3p overexpression decreased the stemness of 3D cultured cells. In conclusion, our results demonstrate that miR-29b-3p could be a sensitizer of radiation killing in CSC-like cells via inhibiting oncogenes expression. MiR-29b-3p could be a novel therapeutic candidate target for radiotherapy.

High-resolution cross-reactive array for alkaloids.

A high-resolution cross-reactive array capable of classifying alkaloids over a range of concentrations was generated by systematic introduction of a nitroindole analog into a hydrophobic pocket within a DNA three-way junction to match structural motifs presented by the analytes.

Triggered release of an active peptide conjugate from a DNA device by an orally administrable small molecule.

A real tonic: In a conceptually new approach to controlled release, the natural daily insulin profile in response to three meals is mimicked (see graph) with release of an insulin conjugate from a matrix, triggered by quinine, a component of tonic water.

Augmentation of cellular NAD+ by NQO1 enzymatic action improves age-related hearing impairment.

Age-related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD+ /NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP-1, and PGC-1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD+ levels on aging and age-related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of ß-lapachone (ß-lap), a known plant-derived metabolite that modulates cellular NAD+ by conversion of NADH to NAD+ via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD+ during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro-inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF-κB, p53, and IDH2. However, augmentation of NAD+ by ß-lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD+ levels by pharmacological agents may be a tangible therapeutic option for treating various age-related diseases, including ARHL.

Historical trends of perfluoroalkyl substances (PFASs) in dated sediments from semi-enclosed bays of Korea.

Information is scarce on historical trends of perfluoroalkyl substances (PFASs) in the coastal environment. In this study, four sediment cores were collected from semi-enclosed bays of Korea to investigate the pollution history, contamination profiles, and environmental burden of PFASs. The total PFAS concentrations in sediment cores ranged from 6.61 to 821 pg/g dry weight. The highest concentrations of PFASs were found in surface or sub-surface sediments, indicating on-going contamination by PFASs. Historical trends in PFASs showed a clear increase since the 1980s, which was consistent with the global PFAS consumption pattern. Concentrations of PFASs were dependent on the organic carbon content in sediment cores. PFOS and longer-chain PFASs were predominant in all of the sediment cores. In particular, a large proportion of longer-chain PFASs was observed in the upper layers of the sediment cores from industrialized coastal regions. Inventories and fluxes estimated for PFASs were similar to those for PCDD/Fs.

The contribution of the contingent negative variation (CNV) to goal maintenance.

The dot pattern expectancy (DPX) task has been strongly recommended as a measure of goal maintenance, which is impaired in schizophrenia patients. The current event-related potential (ERP) study was designed mainly to identify the ERP component that could represent the goal maintenance process of the DPX task as indexed by the error rate of the BX vs. AY (EBX-AY). We focused our analysis on the cue-phased contingent negative variation (CNV) and found a significant association between the EBX-AY and the amplitude of the difference wave of cue B vs. cue A (CNVB-A) (for CP3, ß=-0.262, P=0.001; for CPZ, ß=-0.184, P=0.025; for CP4, ß=-0.201, P=0.015). Lower EBX-AY (better goal maintenance) was correlated with larger CNVB-A. Further analysis found a significant association between the error rate of AY condition (EAY) and the amplitude of CNVA (for CP3, ß=-0.180, P=0.029; for CPZ, ß=-0.184, P=0.024; for CP4, ß=-0.208, P=0.011) and a significant association between the error rate of BX condition (EBX) and the amplitude of CNVB-A (for CP3, ß=-0.198, P=0.016; for CPZ, ß=-0.165, P=0.043; for CP4, ß=-0.151, P=0.066), but not the amplitude of the CNVB (all P>0.05). All these results together suggested that the cue-phased CNV could be used to represent the goal maintenance process. Future research needs to verify these results with schizophrenia patients.

Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice.

Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), reduces the ratio of cellular NADPH/NADP+ through the enzymatic action of NQO1. This study assessed whether a reduction in cellular NADPH/NADP+ ratio can be used to regulate caerulein-induced pancreatic damage associated with NOX-induced ROS production in animal models. Dunnione treatment significantly reduced the cellular NADPH/NADP+ ratio and NOX activity through the enzymatic action of NQO1 in the pancreas of the caerulein-injection group. Similar to these results, total ROS production and expressions of mRNA and protein for NOX subunits Nox1, p27phox, p47phox, and p67phox also decreased in the dunnione-treated group. In addition, caerulein-induced pancreatic inflammation and acinar cell injury were significantly reduced by dunnione treatment. This study is the first to demonstrate that modulation of the cellular NADPH:NADP+ ratio by enzymatic action of NQO1 protects acute pancreatitis through the regulation of NOX activity. Furthermore, these results suggest that modulation of the NADPH:NADP+ ratio in cells by NQO1 may be a novel therapeutic strategy for acute pancreatitis.

Patterns and determinants of plant biodiversity in non-commercial forests of eastern China.

Non-commercial forests represent important habitats for the maintenance of biodiversity and ecosystem function in China, yet no studies have explored the patterns and determinants of plant biodiversity in these human dominated landscapes. Here we test the influence of (1) forest type (pine, mixed, and broad-leaved), (2) disturbance history, and (3) environmental factors, on tree species richness and composition in 600 study plots in eastern China. In total, we found 143 species in 53 families of woody plants, with a number of species rare and endemic in the study region. Species richness in mixed forest and broad-leaved forest was higher than that in pine forest, and was higher in forests with less disturbance. Species composition was influenced by environment factors in different ways in different forest types, with important variables including elevation, soil depth and aspect. Surprisingly, we found little effect of forest age after disturbance on species composition. Most non-commercial forests in this region are dominated by species poor pine forests and mixed young forests. As such, our results highlight the importance of broad-leaved forests for regional plant biodiversity conservation. To increase the representation of broad-leaved non-commercial forests, specific management practices such as thinning of pine trees could be undertaken.

Increased Prevalence of Severe Fever with Thrombocytopenia Syndrome in Eastern China Clustered with Multiple Genotypes and Reasserted Virus during 2010-2015.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne viral disease with high mortality. Since January 2010, we have conducted an epidemiological surveillance and etiological study of SFTS in Jiangsu and Anhui provinces. From January 2010 through December 2015, a total of 286 SFTS cases were confirmed in Jiangsu and Anhui provinces with a case fatality rate of 16.1%. The majority of confirmed SFTS cases were distributed in the border area of Jiangsu and Anhui provinces. Our findings suggest that the SFTS prevalence rate rose since 2010 and reached its highest in 2015. Phylogenetic analysis demonstrated that the majority of the SFTSV strains (83.6%) from Jiangsu and Anhui provinces belonged to genotypes A and D. Notably, we identified three strains of SFTSV clustered into the genotype E. This is the first report of the genotype E SFTSV strains in mainland of China. A reassortment between genotype A and D was found in the central region of the endemic areas, where three SFTSV genotypes (A, C and D) were co-circulating.