Nucleotide-binding leucine-rich repeat receptor homologs Pib and PibH8 interact and contribute to immunity in rice.

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) sense pathogen effectors and activate effector-triggered immunity (ETI). Many plant NLRs form pairs with other NLRs to recognize effectors and initiate ETI. PIRICULARIA ORYZAE RESISTANCE IN BL1 (Pib), an NLR protein in rice (Oryza sativa), activates resistance by recognizing the rice blast effector AvrPib. The activation of Pib is suppressed by SH3 DOMAIN-CONTAINING PROTEIN 2 (OsSH3P2) in the absence of AvrPib. However, how Pib triggers defense responses and whether Pib pairs with another NLR are not clear. In this study, we identified Pib by map-based cloning and showed that a homolog of Pib, PIB HOMOLOGUE 8 (PibH8), interacts with Pib. Pib and PibH8 mediate resistance to the Magnaporthe oryzae isolate Guy11, a rice blast strain carrying AvrPib. Interestingly, the pib/pibh8 double mutant exhibited enhanced susceptibility to Guy11 compared to the single mutant. Furthermore, PibH8 can oligomerize through its coiled-coil (CC) domain, which also contributes to the Pib-PibH8 interaction, suggesting that Pib and PibH8 may form a complex to recognize AvrPib. OsSH3P2 inhibited the interaction of Pib and PibH8 through association with the CC domain of PibH8. Taken together, these results indicate that both Pib and PibH8 are required for rice blast resistance to M. oryzae carrying AvrPib, which is negatively regulated by OsSH3P2. This study not only identifies an NLR that functions in rice blast resistance but also reveals a possible complex immune strategy in which homologous NLR proteins may regulate the complete activation of plant immunity.

Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration.

BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.

Triglyceride-glucose index and glycemic dynamics in pancreatic ductal adenocarcinoma: implications for disease progression and prognosis.

BACKGROUND: To elucidate the relationship between the triglyceride-glycemic index (TyG) and clinical characteristics of pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 1,594 individuals diagnosed with pancreatic and periampullary neoplasms were categorized into four groups: PDAC-early (n = 403), locally advanced PDAC (LAPC, n = 315), PDAC-late with distant metastasis (n = 371), and other tumor types (n = 505). TyG-high was defined as a TyG index greater than 8.81 in males and 8.73 in females. RESULTS: The prevalence of TyG-high status was highest in PDAC-early (68.48%), followed by LAPC (53.33%), and lowest in PDAC-late (44.47%). TyG-high status significantly predicted worse PDAC prognosis (P = 0.0166), particularly in PDAC-late (P = 0.0420). Despite similar blood glucose levels across PDAC groups (P = 0.897), PDAC-early patients showed significantly higher rates of glycemic disturbances (56.33% vs. 32.28%) and TyG-high status (68.48% vs. 47.13%) compared to those with other tumors. Progressive increases in glycemic disturbances and TyG-high status were observed from benign to pre-malignant lesions and PDAC-early. PDAC-early patients at the pancreatic head exhibited higher rates of glycemic disturbances (58.12% vs. 33.33%, P < 0.0001), larger pancreatic duct diameters (0.4056 cm vs. 0.3398 cm, P = 0.0043), and poorer prognosis compared to periampullary cancers, although the TyG-high rate and body mass index were similar. CONCLUSION: The TyG index exhibits a complex association with PDAC stages, profoundly shaping glycemic profiles. At the initial stages of PDAC, a notable elevation in TyG-high status and glycemic disturbances is observed. However, in advanced PDAC, while the TyG-high rate diminishes, abnormal glucose levels persist.

OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated transcriptional regulation of immune-related genes.

Mitogen-activated protein kinase (MAPK) signalling cascades are functionally important signalling modules in eukaryotes. Transcriptome reprogramming of immune-related genes is a key process in plant immunity. Emerging evidence shows that plant MAPK cascade is associated with processing (P)-body components and contributes to transcriptome reprogramming of immune-related genes. However, it remains largely unknown how this process is regulated. Here, we show that OsMPK12, which is induced by Magnaporthe oryzae infection, positively regulates rice blast resistance. Further analysis revealed that OsMPK12 directly interacts with enhancer of mRNA decapping protein 4 (OsEDC4), a P-body-located protein, and recruits OsEDC4 to where OsMPK12 is enriched. Importantly, OsEDC4 directly interacts with two decapping complex members OsDCP1 and OsDCP2, indicating that OsEDC4 is a subunit of the mRNA decapping complex. Additionally, we found that OsEDC4 positively regulates rice blast resistance by regulating expression of immune-related genes and maintaining proper mRNA levels of some negatively-regulated genes. And OsMPK12 and OsEDC4 are also involved in rice growth and development regulation. Taken together, our data demonstrate that OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated mRNA decay of immune-related genes, providing new insight into not only the new role of the MAPK signalling cascade, but also posttranscriptional regulation of immune-related genes.

Receptor-like kinases OsRLK902-1 and OsRLK902-2 form immune complexes with OsRLCK185 to regulate rice blast resistance.

Receptor-like kinases (RLKs) are major regulators of the plant immune response and play important roles in the perception and transmission of immune signals. RECEPTOR LIKE KINASE 902 (RLK902) is at the key node in leucine-rich repeat receptor-like kinase interaction networks and positively regulates resistance to the bacterial pathogen Pseudomonas syringae in Arabidopsis. However, the function of RLK902 in fungal disease resistance remains obscure. In this study, we found that the expression levels of OsRLK902-1 and OsRLK902-2, encoding two orthologues of RLK902 in rice, were induced by Magnaporthe oryzae, chitin, and flg22 treatment. osrlk902-1 and osrlk902-2 knockout mutants displayed enhanced susceptibility to M. oryzae. Interestingly, the osrlk902-1 rlk902-2 double mutant exhibited similar disease susceptibility, hydrogen peroxide production, and callose deposition to the two single mutants. Further investigation showed that OsRLK902-1 interacts with and stabilizes OsRLK902-2. The two OsRLKs form a complex with OsRLCK185, a key regulator in chitin-triggered immunity, and stabilize it. Taken together, our data demonstrate that OsRLK902-1 and OsRLK902-2, as well as OsRLCK185 function together in regulating disease resistance to M. oryzae in rice.

Phase II study of SOXIRI (S-1/oxaliplatin/irinotecan) chemotherapy in patients with unresectable pancreatic ductal adenocarcinoma.

BACKGROUND: To provide data on the safety and efficacy of a combination chemotherapy regimen consisting of S-1, oxaliplatin, and irinotecan (SOXIRI) as a first-line therapy in unresectable pancreatic ductal adenocarcinoma (UPDA) patients. METHODS: Patients with UPDA and no prior treatment chemotherapy in the UPDA setting were enrolled. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. Patients received 80 mg/m2 S-1 twice a day for 2 weeks in an alternate-day administration cycle, 85 mg/m2 oxaliplatin on Day 1, and 150 mg/m2 irinotecan on Day 1 of a 2-week cycle. RESULTS: In these 62 enrolled patients, the ORR was 27.4 %, median OS was 12.1 months, and median PFS was 6.5 months. Major grade 3 or 4 toxicity included neutropenia (22.3 %), leucopenia (16.1 %), nausea (9.7 %), vomiting (9.7 %), thrombocytopenia (6.5 %), anorexia (8.5 %), anemia (4.8 %), and diarrhea (1.6 %). No treatment-related deaths occurred. In addition, the analysis of 32 patients suffering pain revealed that the rate of pain relief was 34.4 %. CONCLUSION: SOXIRI might be a standard regimen with an acceptable toxicity profile and favorable efficacy for use as chemotherapy in patients with UPDA.

Predicting the therapeutic response to valproic acid in childhood absence epilepsy through electroencephalogram analysis using machine learning.

Childhood absence epilepsy (CAE) is a common type of idiopathic generalized epilepsy, manifesting as daily multiple absence seizures. Although seizures in most patients can be adequately controlled with first-line antiseizure medication (ASM), approximately 25 % of patients respond poorly to first-line ASM. In addition, an accurate method for predicting first-line medication responsiveness is lacking. We used the quantitative electroencephalogram (QEEG) features of patients with CAE along with machine learning to predict the therapeutic effects of valproic acid in this population. We enrolled 25 patients with CAE from multiple medical centers. Twelve patients who required additional medication for seizure control or who were shifted to another ASM and 13 patients who achieved seizure freedom with valproic acid within 6 months served as the nonresponder and responder groups. Using machine learning, we analyzed the interictal background EEG data without epileptiform discharge before ASM. The following features were analyzed: EEG frequency bands, Hjorth parameters, detrended fluctuation analysis, Higuchi fractal dimension, Lempel-Ziv complexity (LZC), Petrosian fractal dimension, and sample entropy (SE). We applied leave-one-out cross-validation with support vector machine, K-nearest neighbor (KNN), random forest, decision tree, Ada boost, and extreme gradient boosting, and we tested the performance of these models. The responders had significantly higher alpha band power and lower delta band power than the nonresponders. The Hjorth mobility, LZC, and SE values in the temporal, parietal, and occipital lobes were higher in the responders than in the nonresponders. Hjorth complexity was higher in the nonresponders than in the responders in almost all the brain regions, except for the leads FP1 and FP2. Using KNN classification with theta band power in the temporal lobe yielded optimal performance, with sensitivity of 92.31 %, specificity of 76.92 %, accuracy of 84.62 %, and area under the curve of 88.46 %.We used various EEG features along with machine learning to accurately predict whether patients with CAE would respond to valproic acid. Our method could provide valuable assistance for pediatric neurologists in selecting suitable ASM.

Effect of dietary selenium intake on CVD: a retrospective cohort study based on China Health and Nutrition Survey (CHNS) data.

OBJECTIVE: We aimed to examine the association between dietary Se intake and CVD risk in Chinese adults. DESIGN: This prospective cohort study included adults above 20 years old in the China Health and Nutrition Survey (CHNS), and they were followed up from 1997 to 2015 (n 16 030). Dietary data were retrieved from CHNS, and a 3-d, 24-h recall of food intake was used to assess the cumulative average intake of dietary Se, which was divided into quartiles. The Cox proportional hazards model was adopted to analyse the association between dietary Se intake and incident CVD risk. SETTING: CHNS (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011 and 2015). RESULTS: A total of 663 respondents developed CVD after being followed up for a mean of 9·9 years (median 9 years). The incidence of CVD was 4·3, 3·7, 4·6 and 4·0 per 1000 person-years across the quartiles of cumulative Se intake. After adjusting all potential factors, no significant associations were found between cumulative Se intake and CVD risk. No interactions were found between Se intake and income, urbanisation, sex, region, weight, hypertension and CVD risk. CONCLUSION: We found no association between dietary Se and CVD.

Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy versus Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Disorders: A Meta-Analysis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. METHODS: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. RESULTS: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p < 0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). CONCLUSION: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

Food safety-related practices among residents aged 18-75 years during the COVID-19 pandemic: a cross-sectional study in Southwest China.

BACKGROUND: Good food safety practices are essential to minimizing foodborne diseases. The present study explored the food safety-related practices of residents during the COVID-19 pandemic in Southwest China and identified the impacting factors. METHODS: Residents aged 18-75 years from Guizhou, Yunnan, Sichuan, and Chongqing, China, were included in our study. The convenience sampling method was used to select participants, and face-to-face surveys were conducted in households and communities to collect data. Descriptive statistics including sociodemographic characteristics of respondents and weighted percentages were obtained and the log-binomial regression was used to evaluate the influencing factors associated with food safety-related practices. RESULTS: Overall, 7,848 respondents were involved, with 97.5% efficacy. Disparities in food safety-related practices were observed between males and females, with the former performing poorer practices than the latter (70.5% vs. 68.0%, respectively). Notably, paying attention to nutrition labels when shopping for prepackaged foods was the worst practice. Age, ethnicity, region, occupation, education level, and income were identified as significant determinants of food safety-related practices. Moreover, in comparison to males, females were more likely to acquire pertinent knowledge from diverse sources, including social media, family members/ friends, books/ newspapers/ magazines, experts, and food sales staff (p < 0.05). CONCLUSIONS: Males performed inferior food safety-related practices than females during the COVID-19 pandemic in Southwest China. It is suggested that future food safety education programs should incorporate diverse targeted approaches, with emphasis on males. The role of mainstream media in promoting food safety practices should be expanded and prioritized in the forthcoming initiatives.

Eddy Current Array for Defect Detection in Finely Grooved Structure Using MSTSA Network.

In this paper, we focus on eddy current array (ECA) technology for defect detection in finely grooved structures of spinning cylinders, which are significantly affected by surface texture interference, lift-off distance, and mechanical dither. Unlike a single eddy current coil, an ECA, which arranges multiple eddy current coils in a specific configuration, offers not only higher accuracy and efficiency for defect detection but also the inherent properties of space and time for signal acquisition. To efficiently detect defects in finely grooved structures, we introduce a spatiotemporal self-attention mechanism to ECA testing, enabling the detection of defects of various sizes. We propose a Multi-scale SpatioTemporal Self-Attention Network for defect detection, called MSTSA-Net. In our framework, Temporal Attention (TA) and Spatial Attention (SA) blocks are incorporated to capture the spatiotemporal features of defects. Depth-wise and point-wise convolutions are utilized to compute channel weights and spatial weights for self-attention, respectively. Multi-scale features of space and time are extracted separately in a pyramid manner and then fused to regress the bounding boxes and confidence levels of defects. Experimental results show that the proposed method significantly outperforms not only traditional image processing methods but also state-of-the-art models, such as YOLOv3-SPP and Faster R-CNN, with fewer parameters and lower FLOPs in terms of Recall and F1 score.

OsCAMTA3 Negatively Regulates Disease Resistance to Magnaporthe oryzae by Associating with OsCAMTAPL in Rice.

Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the response to biotic stresses. In this study, we showed that OsCAMTA3 and CAMTA PROTEIN LIKE (OsCAMTAPL), an OsCAMTA3 homolog that lacks the DNA-binding domain, functioned together in negatively regulating disease resistance in rice. OsCAMTA3 associated with OsCAMTAPL. The oscamta3 and oscamtapl mutants showed enhanced resistance compared to wild-type plants, and oscamta3/pl double mutants showed more robust resistance to M. oryzae than oscamta3 or oscamtapl. An RNA-Seq analysis revealed that 59 and 73 genes, respectively, were differentially expressed in wild-type plants and oscamta3 before and after inoculation with M. oryzae, including OsALDH2B1, an acetaldehyde dehydrogenase that negatively regulates plant immunity. OsCAMTA3 could directly bind to the promoter of OsALDH2B1, and OsALDH2B1 expression was decreased in oscamta3, oscamtapl, and oscamta3/pl mutants. In conclusion, OsCAMTA3 associates with OsCAMTAPL to regulate disease resistance by binding and activating the expression of OsALDH2B1 in rice, which reveals a strategy by which rice controls rice blast disease and provides important genes for resistance breeding holding a certain positive impact on ensuring food security.

The receptor-like cytoplasmic kinase OsBSK1-2 regulates immunity via an HLH/bHLH complex.

Plants need to fine-tune defense responses to maintain a robust but flexible host barrier to various pathogens. Helix-loop-helix/basic helix-loop-helix (HLH/bHLH) complexes play important roles in fine-tuning plant development. However, the function of these genes in plant immunity and how they are regulated remain obscure. Here, we identified an atypical bHLH transcription factor, Oryza sativa (Os)HLH46, that interacts with rice receptor-like cytoplasmic kinase (RLCK) Os BRASSINOSTEROID-SIGNALING KINASE1-2 (OsBSK1-2), which plays a key role in rice blast resistance. OsBSK1-2 stabilized OsHLH46 both in vivo and in vitro. In addition, OsHLH46 positively regulates rice blast resistance, which depends on OsBSK1-2. OsHLH46 has no transcriptional activation activity and interacts with a typical bHLH protein, OsbHLH6, which negatively regulates rice blast resistance. OsbHLH6 binds to the promoter of OsWRKY45 and inhibits its expression, while OsHLH46 suppresses the function of OsbHLH6 by blocking its DNA binding and transcriptional inhibition of OsWRKY45. Consistent with these findings, OsWRKY45 was up-regulated in OsHLH46-overexpressing plants. In addition, the oshlh46 mutant overexpressing OsbHLH6 is more susceptible to Magnaporthe oryzae than is the wild type, suggesting that OsHLH46 suppresses OsbHLH6-mediated rice blast resistance. Our results not only demonstrated that OsBSK1-2 regulates rice blast resistance via the OsHLH46/OsbHLH6 complex, but also uncovered a new mechanism for plants to fine-tune plant immunity by regulating the HLH/bHLH complex via RLCKs.

The landscape of objective response rate of anti-PD-1/L1 monotherapy across 31 types of cancer: a system review and novel biomarker investigating.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment. However, only a few patients respond to ICI treatment. Thus, uncovering clinically accessible ICI biomarkers would help identify which patients will respond well to ICI treatment. A comprehensive objective response rate (ORR) data of anti-PD-1/PD-L1 monotherapy in pan-cancer would offer the original data to explore the new biomarkers for ICIs. METHODS: We systematically searched PubMed, Cochrane, and Embase for clinical trials on July 1, 2021, limited to the years 2017-2021, from which we obtained studies centering around anti-PD-1/PD-L1 monotherapy. Finally, 121 out of 3099 publications and 143 ORR data were included. All of the 31 tumor types/subtypes can be found in the TCGA database. The gene expression profiles and mutation data were downloaded from TCGA. A comprehensive genome-wide screening of ORR highly correlated mutations among 31 cancers was conducted by Pearson correlation analysis based on the TCGA database. RESULTS: According to the ORR, we classified 31 types of cancer into high, medium, and low response types. Further analysis uncovered that "high response" cancers had more T cell infiltration, more neoantigens, and less M2 macrophage infiltration. A panel of 28 biomarkers reviewed from recent articles were investigated with ORR. We also found the TMB as a traditional biomarker had a high correlation coefficient with ORR in pan-cancer, however, the correlation between ITH and ORR was low across pan-cancer. Moreover, we primarily identified 1044 ORR highly correlated mutations through a comprehensive screening of TCGA data, among which USH2A, ZFHX4 and PLCO mutations were found to be highly correlated to strengthened tumor immunogenicity and inflamed antitumor immunity, as well as improved outcomes for ICIs treatment among multiple immunotherapy cohorts. CONCLUSION: Our study provides comprehensive data on ORR of anti-PD-1/PD-L1 monotherapy across 31 tumor types/subtypes and an essential reference of ORR to explore new biomarkers. We also screened out a list of 1044 immune response related genes and we showed that USH2A, ZFHX4 and PLCO mutations may act as good biomarkers for predicting patient response to anti-PD-1/PD-L1 ICIs.

Comparison the efficacy and safety of different neoadjuvant regimens for resectable and borderline resectable pancreatic cancer: a systematic review and network meta-analysis.

BACKGROUND: To date, the optimal recommended specific neoadjuvant regimens for resectable or borderline resectable pancreatic cancer (RPC or BRPC) remain an unanswered issue. METHODS: We systematically searched the electronic databases to identify randomized controlled trials (RCTs) comparing different neoadjuvant therapy strategies for RPC or BRPC. The primary outcome was overall survival (OS). Comprehensive analyses and evaluations were performed using the single-arm, paired, and network meta-analyses. RESULTS: Twelve RCTs involving 1279 patients with RPC or BRPC were enrolled. The paired meta-analysis showed that neoadjuvant therapy improved OS for both RPC (hazard ratio (HR) 0.69, 95% c.i. 0.54 to 0.87) and BRPC (HR 0.60, 0.42 to 0.86) compared with upfront surgery (UP-S). Neoadjuvant chemotherapy (NAC) also improved OS for both RPC (HR 0.63, 0.47 to 0.85) and BRPC (HR 0.44, 0.27 to 0.71), while neoadjuvant chemoradiotherapy (NACR) improved OS only for BRPC (HR 0.68, 0.52 to 0.89) and not for RPC (HR 0.79, 0.54 to 1.16). Network meta-analysis found that NAC was superior to NACR in OS for RPC/BRPC (HR 0.58, 0.37 to 0.90). Neoadjuvant chemotherapy based on modified fluorouracil/folinic acid/irinotecan/oxaliplatin (NAC-mFFX) and neoadjuvant chemotherapy based on abraxane/gemcitabine (NAC-AG) ranked first and second in OS for RPC/BRPC. CONCLUSIONS: Both RPC and BRPC could obtain OS benefits from neoadjuvant therapy compared with UP-S, and NAC improved OS both in RPC and BRPC while NACR only improved OS in BRPC. Furthermore, NAC was superior to NACR, and NAC-mFFX and NAC-AG might be recommended sequentially as the best neoadjuvant therapy strategies.

Neem oil against Aeromonas hydrophila infection by disrupting quorum sensing and biofilm formation.

Aeromonas hydrophila is an opportunistic pathogen that can cause a number of infectious diseases in fish and is widely distributed in aquatic environments. Antibiotics are the main approach against A. hydrophila infections, while the emergence of resistant bacteria limits the application of antibiotics. Here, quorum-sensing (QS) was defined as the target and the inhibitory effects of neem oil against QS of A. hydrophila was studied. The results showed that neem oil could dose-dependently reduce aerolysin, protease, lipase, acyl-homoserine lactones (AHLs), biofilm and swarming motility at sub-inhibitory concentrations. Results of real-time PCR demonstrated that neem oil could down-regulate the transcription of aerA, ahyI and ahyR. Moreover, neem oil showed significant protections to A549 cells and a fish infection model. Taken together, these results indicated that neem oil could be chosen as a promising candidate for the treatment of A. hydrophila infections.

The Diagnostic and Prognostic Value of EBUS-TBNA for Intrathoracic Metastasis in Previously Treated Patients With Head and Neck Cancer.

OBJECTIVE: The present study assessed the diagnostic and prognostic significance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for suspected intrathoracic metastasis after HNC treatment. METHODS: A retrospective analysis was conducted on 75 patients with a prior history of head and neck cancer treatment who underwent EBUS-TBNA for suspected intrathoracic metastases between March 2012 and December 2021. RESULTS: A total of 126 targeted lesions, including 107 mediastinal/hilar lymph nodes and 19 intrapulmonary/mediastinal masses, were sampled. The metastatic head and neck cancer (HNC) cases detected by EBUS-TBNA consisted of nasopharyngeal carcinoma (n = 24), oropharyngeal carcinoma (n = 3), hypopharynx carcinoma (n = 6), laryngeal carcinoma (n = 6), and oral cavity carcinoma (n = 6). Cases with negative EBUS-TBNA results consisted of tuberculosis (n = 9), sarcoidosis (n = 3), anthracosis (n = 9), and reactive lymphadenitis (n = 9). Six false-negative cases were found among the 75 patients with suspected intrathoracic metastases. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the EBUS-TBNA procedure for metastatic HNC were 88.2, 100.0, 100.0, 80, and 92.0%, respectively. The diagnosis of HNC intrathoracic metastasis by EBUS-TBNA correlated with an adverse prognosis in terms of overall survival (OS) (P = .008). The log-rank univariate analysis and Cox regression multivariate analysis results indicated that the detection of metastatic HNC through EBUS-TBNA was a significant independent prognostic factor for patients with HNC who had received prior treatment. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial needle aspiration is a safe, effective, and minimally invasive procedure for assessing suspected intrathoracic metastasis in HNC patients after treatment. The intrathoracic metastasis detected by EBUS-TBNA has crucial prognostic significance in previously treated HNC patients.

The enhanced cell cycle related to the response to adjuvant therapy in pancreatic ductal adenocarcinoma.

A major clinical challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) is identifying those that may benefit from adjuvant chemotherapy versus those that will not. Thus, there is a need for a robust and convenient biomarker for predicting chemotherapy response in PDAC patients. In this study, network inference was conducted by integrating the differentially expressed cell cycle signatures and target genes between the basal-like subtype and classical subtype of PDAC. As a result from this statistical analysis, two dominant cell cycle genes, RASAL2 and ASPM, were identified. Based on the expression levels of these two genes, we constructed a "Enhanced Cell Cycle" scoring system (ECC score). Patients were given an ECC score, and respectively divided into ECC-high and ECC-low groups. Survival, pathway enrichment, immune environment characteristics, and chemotherapy response analysis' were performed between the two groups in a total of 891 patients across 5 cohorts. ECC-high patients exhibited shortened recurrence-free survival (RFS) and overall survival (OS) rates. In addition, it was found that adjuvant chemotherapy could significantly improve the outcome of the ECC-high patients while ECC-low patients did not benefit from adjuvant chemotherapy. It was also found that there was less CD8+ T cell, natural killer (NK) cell, M1 macrophage, and plasma cell infiltration in ECC-high patients when compared to ECC-low patients. Also, the expression of CD73, an immune suppressor gene, and it's related hypoxia pathway were elevated in the ECC-high group when compared to the ECC-low group. In conclusion, this study showed that patients characterized as ECC-high not only had reduced RFS and OS rates, but were also more sensitive to adjuvant chemotherapy and could potentially be less sensitive to immune checkpoint inhibitors. Being able to characterize patients by these parameters would allow doctors to make more informed decisions on patient treatment regimens.

Position Tracking of Multiple Robotic Manipulator Systems Associated with Communication Strength Dynamics.

In general, a multiple robotic manipulator system (MRMS) with uncertainties can be considered a composition system with a robotic manipulator subsystem (RMS) and a communication strength subsystem (CSS), and both subsystems are coupled to each other. In this paper, a new position tracking control scheme is proposed for the MRMS while considering the communication strength dynamics between robotic manipulators. The control scheme designed in this paper consists of two parts: the first part is to design the control protocol in the RMS, and the second part is to design the coupling relationship in the CSS. Through these two parts, we can achieve the position tracking of an MRMS. Firstly, the dynamical mathematical model of the RMS and CSS in the MRMS is constructed, and the corresponding assumptions are given. Then, the corresponding stability analysis is proposed, which provides the basis for a theoretical understanding of the underlying problem. Finally, an illustrative example is presented to verify the effectiveness of the proposed control scheme.

Partial substitution of manure reduces nitrous oxide emission with maintained yield in a winter wheat crop.

Conventional fertilization of agricultural soils results in increased N2O emissions. As an alternative, the partial substitution of organic fertilizer may help to regulate N2O emissions. However, studies assessing the effects of partial substitution of organic fertilizer on both N2O emissions and yield stability are currently limited. We conducted a field experiment from 2017 to 2021 with six fertilizer regimes to examine the effects of partial substitution of manure on N2O emissions and yield stability. The tested fertilizer regimes, were CK (no fertilizer), CF (chemical fertilizer alone, N 300 kg ha-1, P2O5 150 kg ha-1, K2O 90 kg ha-1), CF + M (chemical fertilizer + organic manure), CFR (chemical fertilizer reduction, N 225 kg ha-1, P2O5 135 kg ha-1, K2O 75 kg ha-1), CFR + M (chemical fertilizer reduction + organic manure), and organic manure alone (M). Our results indicate that soil N2O emissions are primarily regulated by soil mineral N content in arid and semi-arid regions. Compared with CF, N2O emissions in the CF + M, CFR, CFR + M, and M treatments decreased by 16.8%, 23.9%, 42.0%, and 39.4%, respectively. The highest winter wheat yields were observed in CF, followed by CF + M, CFR, and CFR + M. However, the CFR + M treatment exhibited lower N2O emissions while maintaining high yield, compared with CF. Four consecutive years of yield data from 2017 to 2021 illustrated that a single application of organic fertilizer resulted in poor yield stability and that partial substitution of organic fertilizer resulted in the greatest yield stability. Overall, partial substitution of manure reduced N2O emissions while maintaining yield stability compared with the synthetic fertilizer treatment during the wheat growing season. Therefore, partial substitution of manure can be recommended as an optimal N fertilization regime for alleviating N2O emissions and contributing to food security in arid and semi-arid regions.