Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3.

Porcine deltacoronavirus (PDCoV) has caused enormous economic losses to the global pig industry. However, the immune escape mechanism of PDCoV remains to be fully clarified. Transcriptomic analysis revealed a high abundance of interferon (IFN)-induced protein with tetratricopeptide repeats 3 (IFIT3) transcripts after PDCoV infection, which initially implied a correlation between IFIT3 and PDCoV. Further studies showed that PDCoV nsp5 could antagonize the host type I interferon signaling pathway by cleaving IFIT3. We demonstrated that PDCoV nsp5 cleaved porcine IFIT3 (pIFIT3) at Gln-406. Similar cleavage of endogenous IFIT3 has also been observed in PDCoV-infected cells. The pIFIT3-Q406A mutant was resistant to nsp5-mediated cleavage and exhibited a greater ability to inhibit PDCoV infection than wild-type pIFIT3. Furthermore, we found that cleavage of IFIT3 is a common characteristic of nsp5 proteins of human coronaviruses, albeit not alphacoronavirus. This finding suggests that the cleavage of IFIT3 is an important mechanism by which PDCoV nsp5 antagonizes IFN signaling. Our study provides new insights into the mechanisms by which PDCoV antagonizes the host innate immune response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence and pathogenesis of PDCoV are ongoing. The main protease (nsp5) of PDCoV provides an excellent target for antivirals due to its essential and conserved function in the viral replication cycle. Previous studies have revealed that nsp5 of PDCoV antagonizes type I interferon (IFN) production by targeting the interferon-stimulated genes. Here, we provide the first demonstration that nsp5 of PDCoV antagonizes IFN signaling by cleaving IFIT3, which affects the IFN response after PDCoV infection. Our findings reveal that PDCoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by deltacoronaviruses.

Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1ß, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines. CONCLUSION: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022. WHAT IS KNOWN: • Inflammation is an important secondary physiological response to TBI. WHAT IS NEW: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study.

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.

Effect of intravenous immunoglobulin on the outcome of children with septic shock in a PICU: a retrospective cohort study.

The therapeutic efficacy of intravenous immuneglobulin (IVIG) on children with septic shock remains uncertain. Therefore, we endeavored to investigate the impact of administering intravenous immunoglobulin (IVIG) in the pediatric intensive care unit (PICU) on patient with septic shock. We retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2017 to December 2021 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. Total 304 patients were enrolled. There were no significant differences in the PRISM-III score (11 vs. 12, P = 0.907), PIM-3 score (0.08 vs. 0.07, P = 0.544), pSOFA score (10 vs. 10, P = 0.852) between the No IVIG group and the IVIG group. Children who received IVIG required more continuous renal replacement therapy (CRRT) support (43% vs. 24%, P = 0.001) and longer duration of mechanical ventilation (MV) (6 vs. 3 days, P = 0.002), and longer length of stay (LOS) of PICU (7 vs. 4 days, P = 0.001) and LOS of hospital (18 vs. 11 days, P = 0.001) than children who did not receive. The 28-day survival analysis (P = 0.033) showed better survival rates in IVIG group, while the in-hospital mortality (43% vs. 52%, P = 0.136) was no significant difference. In the propensity score matched analysis, 71 pairs were established. The length of CRRT (2 vs. 3 days, P = 0.744), duration of mechanical ventilation (5 vs. 4 days, P = 0.402), LOS of PICU (7 vs. 5 days, P = 0.216), LOS of hospital (18 vs. 13 days, P = 0.290), in-hospital mortality (44% vs. 44%, P = 1.000) and 28-day survival analysis (P = 0.748) were not statistically different. After inverse probability weighted analysis, there was still no difference in mortality between the two groups (51% vs. 48%, P = 0.665). CONCLUSION: In children with septic shock, the use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality. WHAT IS KNOWN: • Guidelines suggest against the routine use of intravenous immuneglobulin in children with septic shock. Some small observational studies have reported conflicting result. WHAT IS NEW: • The use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality in children with septic shock.

Association of Epstein-Barr virus DNA and SAA with S1 maintenance therapy outcomes in patients with metastatic nasopharyngeal carcinoma.

Objectives: The relevant biomarkers in predicting maintenance therapy (MT) outcomes in metastatic nasopharyngeal carcinoma (NPC) are yet unclear. Patients & methods: Metastatic NPC patients were randomly divided into MT (S1-MT) and non-MT groups. The association of Epstein-Barr virus DNA (EBV-DNA) and SAA with survival was assessed. Results: A total of 183 patients were included. S1-MT significantly increased the progression-free survival (PFS) and overall survival (OS) of the metastatic NPC patients (both p < 0.001). For patients who were EBV-DNA positive or had decreased SAA, the PFS and OS increased significantly after S1-MT (both p < 0.001), while patients with stable SAA did not benefit from S1-MT. Conclusion: S1-MT improved the PFS and OS of metastatic NPC patients. EBV-DNA and SAA status were closely associated with the outcomes of S1-MT. Clinical trial registration number: ChiCTR-IOR-16007939.

Randomized and dose-escalation trials of recombinant human serum albumin /granulocyte colony-stimulating factor in patients with breast cancer receiving anthracycline-containing chemotherapy.

BACKGROUND: To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. METHODS: The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 µg, 2100 µg, and 2400 µg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 µg and rhG-CSF 5 µg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 µg, 1500 µg, and continuous rhG-CSF 5 µg/kg. RESULTS: Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 µg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 µg to 2400 µg, while the double delivery of HSA/G-CSF 2400 µg failed to meet the noninferiority in comparison with rhG-CSF. CONCLUSION: The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 µg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

First detection and complete genome analysis of the Lyon IARC polyomavirus in China from samples of diarrheic cats.

Lyon IARC polyomavirus (LIPyV), a newly discovered polyomavirus (PyV), was first identified in 2017 in human skin samples in the USA. Later, it was detected in several other countries in samples of human and feline origin. Our aim was to find out if the virus occurs in China. To this end, 100 fecal samples were collected from cats with diarrhea in Guangxi Province during 2016 and 2018 and tested with polymerase chain reaction (PCR). Only 2 samples that originated from two related individuals were found to be positive. Based on the sequence identity of the 240-bp PCR products, the two positive samples supposedly contained identical viruses. Therefore, only one of them, which was designated as LIPyV-GXNN01, was selected for full genome amplification, cloning, sequencing and analysis. LIPyV-GXNN01, which comprises 5,263 nucleotides, has an early region that consists of small T antigen (ST-Ag) and large T antigen (LT-Ag) and a late region coding for the VP1, VP2, and VP3 structural proteins. Moreover, the LIPyV-GXNN01 strain structural proteins share 95.9-99.4%, 97.6-99.2%, and 97.1-99.2% nucleic acid identity with the VP1, VP2, and VP3of other LIPyV reference strains, respectively. A phylogenetic analysis revealed that GXNN01 clustered together with previously reported LIPyV strain. This present study is the first report of LIPyV in China.

Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang.

BACKGROUND: There are obviously ethnic differences between the UGT1A1 gene polymorphisms. Due to the difference of genetic background and environment, the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. METHODS: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled. The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1*28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. RESULTS: UGT1A1*28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8, 30.2 and 0%, respectively. UGT1A1*6 wild type (G/G), heterozygous mutation type (G/A) and homozygous mutant (A/A) accounted for 76.7%, 20.9 and 2.3%, respectively. UGT1A1*28 TA6/7 type could increase the risk of grade 3~4 diarrhea (p = 0.027), which did not increase the risk of grade 3~4 neutropenia (p = 0.092). UGT1A1*6G/A and A/A type could increase the risk of grade 3~4 diarrhea and neutropenia (p = 0.001; p = 0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p = 0.729; p = 0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1*28 and UGT1A1*6 (7.0 m vs 7.4 m, p = 0.427; 6.9 m vs 7.0 m p = 0.408). CONCLUSIONS: The distribution of UGT1A1*28 and UGT1A1*6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study.

BACKGROUND: Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. METHODS: This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015-2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. RESULTS: A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033). CONCLUSION: For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. TRIAL REGISTRATION: The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Risk factors for mortality in pseudomonas aeruginosa bacteremia in children.

BACKGROUND: The incidence of Pseudomonas aeruginosa (P. aeruginosa) bacteremia in children ranks third to fourth among gram-negative bacilli bacteremia, which is one of the main conditional pathogens in hospitals. This study aimed to identify the clinical characteristics and risk factors of 60-day in-hospital mortality in children with P. aeruginosa bacteremia. METHODS: This retrospective study was conducted in a tertiary pediatric hospital between January 2015 and December 2021 including children with P. aeruginosa bacteremia. Kaplan-Meier survival analysis was used to investigate the time-to-event outcomes. Logistic regression was used to explore the independent risk factors for 60-day mortality. RESULTS: Overall, 75 patients with P. aeruginosa bacteremia episodes were identified. Immunosuppression (52%) was the most common underlying condition, followed by neutropenia (50.7%) and hematological malignancies (48%). Among 75 patients with P. aeruginosa bacteremia, 25 (33.3%) had septic shock, 30 (40%) had respiratory failure, and 20 (26.7%) had liver function impairment. The 60-day in-hospital mortality was 17.3%. In multivariate analysis, independent risk factors for 60-day mortality were respiratory failure [odds ratio (OR) 39.329; 95% CI:3.212-481.48, P = 0.004) and liver function impairment (OR 17.925; 95% CI:2.909-139.178, P = 0.002). CONCLUSION: Respiratory failure and liver function impairment seem to be related to poor prognosis in children with P. aeruginosa bacteremia.

Enhancing secure multi-group data sharing through integration of IPFS and hyperledger fabric.

Data sharing is increasingly important across various industries. However, issues such as data integrity verification during sharing, encryption key leakage, and difficulty sharing data between different user groups have been identified. To address these challenges, this study proposes a multi-group data sharing network model based on Consortium Blockchain and IPFS for P2P sharing. This model uses a dynamic key encryption algorithm to provide secure data sharing, avoiding the problems associated with existing data transmission techniques such as key cracking or data leakage due to low security and reliability. Additionally, the model establishes an IPFS network for users within the group, allowing for the generation of data probes to verify data integrity, and the use of the Fabric network to record log information and probe data related to data operations and encryption. Data owners retain full control over access to their data to ensure privacy and security. The experimental results show that the system proposed in this study has wide applicability.

Adaptive temporal compression for reduction of computational complexity in human behavior recognition.

The research on video analytics especially in the area of human behavior recognition has become increasingly popular recently. It is widely applied in virtual reality, video surveillance, and video retrieval. With the advancement of deep learning algorithms and computer hardware, the conventional two-dimensional convolution technique for training video models has been replaced by three-dimensional convolution, which enables the extraction of spatio-temporal features. Specifically, the use of 3D convolution in human behavior recognition has been the subject of growing interest. However, the increased dimensionality has led to challenges such as the dramatic increase in the number of parameters, increased time complexity, and a strong dependence on GPUs for effective spatio-temporal feature extraction. The training speed can be considerably slow without the support of powerful GPU hardware. To address these issues, this study proposes an Adaptive Time Compression (ATC) module. Functioning as an independent component, ATC can be seamlessly integrated into existing architectures and achieves data compression by eliminating redundant frames within video data. The ATC module effectively reduces GPU computing load and time complexity with negligible loss of accuracy, thereby facilitating real-time human behavior recognition.

Establishment of a chip digital PCR detection method for canine circovirus.

Canine circovirus (CanineCV), which is a new mammalian circovirus first reported in the United States in 2012, mainly causes diarrhea and vomiting in dogs. As CanineCV evolves and new subtypes emerge, there is an urgent need for new detection technologies to improve the sensitivity and detection rates of viruses in complex scenarios. A chip digital PCR(cdPCR) assay was established for the detection of CanineCV in this study. The results showed good reproducibility, specificity and a linear relationship; the minimum detection limit of CanineCV by cdPCR was 6.62 copies/µL, which is 10 times more sensitive than quantitative real-time PCR (qPCR). The qPCR-positive detection rate was 1 %, while CanineCV cdPCR (2.1 %) exhibited a greater positive detection rate. Fifteen complete genomes were sequenced and subdivided into CanineCV-1 and CanineCV-3. In conclusion, we developed a rapid, reliable, and specific cdPCR method for screening and monitoring canine CV.

[Clinical observation of sarcandra glabra combined chemoradiotherapy for treating patients with local advanced nasopharyngeal carcinoma].

OBJECTIVE: To observe the short-term efficacy and radiotherapy induced acute reactions of sarcandra glabra (SG) combined chemoradiotherapy for treating patients with local advanced nasopharyngeal carcinoma. METHODS: Totally 100 nasopharyngeal carcinoma phase III - IVa patients were randomly assigned to the control group and the observation group, 50 patients in each group. All patients received chemoradiotherapy. Patients in the observation group took SG decoction at the daily dose of 20 g. RESULTS: Totally 98 patients completed the treatment. There was no statistical difference in the complete remission rate, the partial remission rate, 1-year and 2-year total survival rates, or disease free progression rate between the two groups. The occurrence rate of II - III degree radioactive oral mucositis and dry mouth were obviously lower in the observation group than in the control group, showing statistical difference (P <0.05). CONCLUSION: SG combined chemoradiotherapy could attenuate radiotherapy induced acute adverse reactions in treating advanced nasopharyngeal carcinoma.

Genetic characterization of Sus scrofa papillomavirus type 1 from domestic pigs in Guangxi Province, China.

Sus scrofa papillomatosis (SsP) is a tumour caused by Sus scrofa papillomaviruses (SsPVs). To investigate the presence of SsPVs in China, 354 domestic pig skin samples collected from Guangxi Province were examined for SsPV DNA by PCR. Three SsPV1s (GX12, GX14, and GX18) were identified with a prevalence of 0.847% (3/354). Sequence analysis showed that L1 of SsPV1/GX12 and SsPV1/GX14 had 99.7% and 99.6% nucleotide identify with the reference SsPV1a, respectively. Phylogenetic and evolutionary analyses showed that SsPV1/GX12 and SsPV1/14 clustered into SsPV1a and that SsPV1/GX18 clustered into SsPV1b. Compared with other SsPV L1 and L2 proteins, we found that the SsPV1/GX18 and SsPV1b strains shared the same unique substitutions, and SsPV1/GX12, SsPV1/GX14, and SsPV1a shared almost identical amino acid sequences. This study reports the first detection of SsPV DNA in China based on whole genome information and provides a scientific basis for the development of SsPV pathogenic biology, epidemiology, and prevention, as well as control technology research.

Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study.

PURPOSE: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers. METHODS: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety. RESULTS: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373-0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227-0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350-0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230-0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1-2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions. CONCLUSION: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO.

Phenol-soluble modulins (PSMs) and Staphylococcal protein A (SpA) are key virulence determinants for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), an important human pathogen that causes a wide range of diseases. Here, using chemical and genetic approaches, we show that inhibition of TarO, the first enzyme in the wall teichoic acid (WTA) biosynthetic pathway, decreases the expression of genes encoding PSMs and SpA in the prototypical CA-MRSA strain USA300 LAC. Mechanistically, these effects are linked to the activation of VraRS two-component system that directly represses the expression of accessory gene regulator (agr) locus and spa. The activation of VraRS was due in part to the loss of the functional integrity of penicillin-binding protein 2 (PBP2) in a PBP2a-dependent manner. TarO inhibition can also activate VraRS in a manner independent of PBP2a. We provide multiple lines of evidence that accumulation of lipid-linked peptidoglycan precursors is a trigger for the activation of VraRS. In sum, our results reveal that WTA biosynthesis plays an important role in the regulation of virulence gene expression in CA-MRSA, underlining TarO as an attractive target for anti-virulence therapy. Our data also suggest that acquisition of PBP2a-encoding mecA gene can impart an additional regulatory layer for the modulation of key signaling pathways in S. aureus.

Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death.

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

Small object detection method with shallow feature fusion network for chip surface defect detection.

The development of intelligent manufacturing often focuses on production flexibility, customization and quality control, which are crucial for chip manufacturing. Specifically, defect detection and classification are important for manufacturing processes in the semiconductor and electronics industries. The intelligent detection methods of chip defects are still challenge and have always been a particular concern of chip processing manufactures in an automated industrial production line. YOLOv4 method has been widely used for object detection due to its accuracy and speed. However, there are still difficulties and challenges in the detection for small targets, especially defects on chip surface. This study proposed a small object detection method based on YOLOv4 for small object in order to improve the performance of detection. It includes expanding feature fusion of shallow features; using k-means++ clustering to optimize the number and size of anchor box; and removing redundant YOLO head network branches to increase detection efficiency. The results of experiments reflect that SO-YOLO is superior to the original YOLOv4, YOLOv5s, and YOLOv5l models in terms of the number of parameters, classification and detection accuracy.