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This paper studies the convex isotonic regression with generalized order restrictions induced by a directed tree. The proposed model covers various intriguing optimization problems with shape or order restrictions, including the generalized nearly isotonic optimization and the total variation on a tree. Inspired by the success of the pool-adjacent-violator algorithm and its active-set interpretation, we propose an active-set-based recursive approach for solving the underlying model. Unlike the brute-force approach that traverses an exponential number of possible active-set combinations, our algorithm has a polynomial time computational complexity under mild assumptions. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC), a heterogeneous subtype of breast cancer (BC), had poor prognosis. Endoplasmic reticulum (ER) stress was responsible for cellular processes and played a crucial role in the cell function. ER stress is a complex and dynamic process that can induce abnormal apoptosis and death. However, the underlying mechanism of ER stress involved in TNBC is not well defined. Methods: We identified ubiquitin‐specific protease 19 (USP19) as a TNBC negative regulator for further investigation. The effects of USP19 on BC proliferation were assessed in vitro using proliferation test and cell‐cycle assays, while the effects in vivo were examined using a mouse tumorigenicity model. Through in vitro flow cytometric analyses and in vivo TUNEL assays, cell apoptosis was assessed. Proteomics was used to examine the proteins that interact with USP19. Results: Multiple in vitro and in vivo tests showed that USP19 decreases TNBC cell growth while increasing apoptosis. Then, we demonstrated that USP19 interacts with deubiquitinates and subsequently stabilises family molecular chaperone regulator 6 (BAG6). BAG6 can boost B‐cell lymphoma 2 (BCL2) ubiquitination and degradation, thereby raising ER calcium (Ca2+) levels and causing ER stress. We also found that the N6‐methyladenosine (m6A) "writer" methyltransferase‐like 14 (METTL14) increased global m6A modification. Conclusions: Our study reveals that USP19 elevates the intracellular Ca2+ concentration to alter ER stress via regulation of BAG6 and BCL2 stability and may be a viable therapeutic target for TNBC therapy. [ABSTRACT FROM AUTHOR]

Township health centers play a cornerstone role in the primary healthcare in China while it's development is largely limited by the brain drain. Job satisfaction is closely related to brain drain, investigating the relevant factors of job satisfaction can provide strategies to reduce brain drain. This research was conducted in Huangpi, China. Convenience sampling methods and self-administereded questionnaires were used. We collected 1370 valid samples, with an effective rate of 97.72%. Descriptive statistics are used to describe sociodemographic information. The Pearson Chi-square statistical was used to test the binary association between job satisfaction and another categorical variable. All the sociodemographic information was applied to the binary logistic regression model using the stepwise selection method. The mean age was 36.98 (SD = 9.84), factors that affect job satisfaction include educational background (x2 = 7.99, p< 0.05), marital status (x2 = 8.96, p< 0.05, monthly income (x2 = 51.43, p< 0.01), hire form (x2 = 7.64, p< 0.05), hours worked per week (x2 = 33.48, p< 0.01), parent had a stable job (x2 = 10.65, p< 0.01). Government and management should consider the impact of current policies on job satisfaction. Increasing the welfare of healthcare staff and promoting equity are potential strategies for improving low levels of job satisfaction. [ABSTRACT FROM AUTHOR]

Morindae Officinalis Radix (MOR) and Alpiniae Oxyphyllae Fructus (AOF) have been widely used as dietary supplements and traditional herbal medicines for centuries. Fungal and mycotoxin contamination in MOR and AOF has been reported recently. In this study, fungi in MOR and AOF are first investigated using DNA metabarcoding, and the differences in fungal microbiome between moldy and non−moldy samples are analyzed. The results show that Ascomycota is the most prevailing fungus at the phylum level in MOR and AOF with relative abundances of 49.53–94.32% and 14.81–81.85%, respectively. Penicillium (1.86–76.14%), Cladosporium (1.82–56.65%), and Trichoderma (0.12–19.71%) are the dominant genera in MOR. Penicillium (0.27–56.06%), Papiliotrema (0.04–51.71%), and Cladosporium (3.08–44.41%) are the dominant genera in AOF. Two potential toxigenic fungi were detected, namely, Trichoderma atroviride and Fusarium equiseti. Moreover, the differences in fungal communities between moldy and non−moldy samples were monitored. In conclusion, DNA metabarcoding can be used to assess the fungal microbiome in edible medicinal herbs, thereby providing a basis for ensuring food safety and drug efficacy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore factors affecting family health management during home quarantine as well as the effects of variations in family health management (FHM) on individuals' health status. Methods: Using stratified random sampling, 618 families in Wuhan as well as cities within its surrounding provinces were recruited and surveyed online. Latent class variables were extracted from four modules: disinfection, space layout, physical exercise, and food reserves. The analysis was conducted using the poLCA package in R software (v.4.1.0). Chi-squared tests, Fisher's exact tests, and non-parametric Kruskal–Wallis tests were used to compare groups as appropriate. Results: We found an overall questionnaire reliability of 0.77 and a total omega of 0.92, indicating that the survey results were credible. The Bayesian information criterion and Akaike information criterion were used to identified four latent class variables, namely latent non-family health management (18.9%) and latent low, medium, and advanced FHM (30.93%, 29.49%, and 20.59%, respectively). Gender, household income level, body mass index, the presence of a nearby community hospital, and self-rated health status showed statistically significant differences with respect to latent FHM. Moreover, we found a statistically significant difference in emotional reactions when comparing latent advanced and low to mid-level latent FHM. Compared with latent non-family health managers, we detected statistically significant differences in individual energy levels between potential family health managers at latent low and medium levels. Additionally, we found statistically significant differences in individual energy levels between latent advanced and low level family health managers. Conclusions: We found that multiple factors, including gender, household income, and body mass index, were correlated with latent FHM during home quarantine. We conclude that FHM can meaningfully improve individuals' health. Thus, increasing social support for individuals can improve FHM as well as individuals' health during home quarantine. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most lethal malignancies with an extremely poor prognosis. In this study, we aim to construct a long noncoding RNA (lncRNA)-based panel biomarker to predict the overall survival of PC patients. The lncRNA expression profiles of PC samples were extracted from The Cancer Genome Atlas (TCGA-PAAD, n = 176) and International Cancer Genome Consortium (PACA-CA, n = 180). We then developed a risk score model according to the lncRNAs expressions from the TCGA-PAAD cohort and further validated it in the PACA-CA cohort. The potential biological functions for the prognostic lncRNAs were investigated using gene set enrichment analysis (GSEA). In the TCGA-PAAD cohort, three lncRNAs (AC009014.3, RP11-48O20.4, and UCA1) were found to be strongly associated with the prognosis of PC. These lncRNAs were integrated to build a three-lncRNA prognostic model that could divide individuals into low- and high-risk groups. Patients of TCGA-PAAD cohort in the high-risk group showed a poorer overall survival than those in the low-risk group (median: 17.3 months vs. 30.4 months, log-rank p < 0.001). Similar results were documented in the PACA-CA cohort (median: 15.2 months vs. 21.0 months, log-rank p < 0.001) and in the stratified analyses by patients' age and TNM stage. In addition, the signature exhibited an independent prognostic power and was significantly correlated with tumor relapse and patients' response to chemotherapy. GSEA indicated that the three-lncRNA signature may be involved in many known biological functions in cancer, especially the epithelial mesenchymal transformation. In conclusion, the identified three-lncRNA signature in our study may serve as a robust and useful prognostic biomarker in PC patients. [ABSTRACT FROM AUTHOR]

Background Both hepatitis B virus (HBV) infection and schistosomiasis are important public health problems in China. Concurrent infection between HBV and schistosomiasis is often observed in areas where schistosomiasis is endemic. The aim of this study was to determine the prevalence of schistosomiasis and HBV in schistosomiasis-affected areas, to explore whether schistosomiasis patients are more susceptible to HBV and to determine if the prevalence of HBV in high-endemic areas of schistosomiasis is higher than in low-endemic areas. Methods A total of 6526 participants from 13 villages in Hubei province were included in a cross-sectional study and blood samples were collected and examined. Qualitative variables were compared between groups using Pearson's chi-squared test or Fisher's exact test as appropriate. Results Of the 6526 participants, the overall prevalence was 8.27% for schistosomiasis and 2.67% for HBV. The prevalence of hepatitis B among participants who were Schistosoma antibody positive (25.37%) was higher than the prevalence in participants who were Schistosoma antibody negative (0.62%; χ2=1169.358, p<0.001, odds ratio 54.659). We also observed that there was no difference in the prevalence of hepatitis B between males and females in areas where schistosomiasis was endemic (χ2=1.827, p=0.177), but the prevalence of hepatitis B in middle-aged people was higher than in other age groups (χ2=47.877, p<0.001). Conclusions There was an association between schistosomiasis and HBV infection. However, more work is needed to find the causal relationship between schistosomiasis and HBV infection. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the effect of socioeconomic status and physical activity on cognitive function using a large population-based survey data in China.Methods: We took advantage of the Chinese Longitudinal Healthy Longevity Survey conducted in 2014 to examine the relationship between sociodemographic, physical activity, and cognitive function in older adults (OAs) for persons aged above 65 (N = 2848). Socioeconomic status was assessed by sex, age, co-residence situation, category of residence, years of schooling, and marital status. Multiple linear regression for predictors was utilized. Physical activity was assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL) measures. Cognitive function was assessed by the Modified Mini-Mental State Examination.Results: The mean age of the OAs was 80.65 years (SD = 8.55). Their mean Mini-Mental State Examination score was 21.55 (SD = 2.38), mean ADL Total score was 6.24 (SD = 0.95), and mean IADL Total score was 10.21 (SD = 3.84). OAs' age at testing, co-residence and category of residence significantly predicted both ADL Total score and IADL Total score (P < 0.05), sex significantly predicted IADL Total score (R2  = 0.02, β = 0.13, P = 0.000) but not ADL Total score (R2  = 0.00, β = 0.02, P = 0.211). OAs' sex, age, co-residence, and years of schooling significantly predicted cognitive function (P < 0.05), IADL total score significantly predicted cognitive function (P < 0.01), while the relationship between ADL total score and cognitive function was not significant (P = 0.94).Conclusion: OAs' sex, age, co-residence, years of schooling, and IADL were significantly associated with cognitive function. Improving OAs' IADL, especially in lower social classes, may help to improve the overall cognitive function of the OAs. [ABSTRACT FROM AUTHOR]

Only when Aquilaria spp. or Gyrinops spp. trees are wounded, due to insect attack, or microbial invasion, agarwood can be successfully induced. In the present study, a fungus which can induce agarwood formation efficiently was isolated and a suitable method for its application to induce agarwood formation was developed. Rigidoporus vinctus was isolated from the inner layers from infectious A. sinensis trees. When the fermentation liquid of fungi inoculated back to A. sinensis tree, agarwood was found to be induced. In addition, a novel method called trunk surface agarwood-inducing technique (Agar-Sit) was developed to produce agarwood with R. vinctus. The alcohol soluble extract content of the agarwood, up to 38.9%, far higher than the requirement (10%) in Chinese Pharmacopoeia and the six characteristic compounds of agarwood used as Chinese Medicinal Materials were all detected. Their relative percentages of the sesquiterpenes in the essential oil were 22.76%. This is the first report of the Agar-Sit and also the application of R. vinctus in agarwood induction. According to the results, when the combination of Agar-Sit and R. vinctus is used agarwood can be induced with high yield and good quality. [ABSTRACT FROM AUTHOR]

Myristicae Semen (nutmeg) has been extensively used for a long time because of its pharmaceutical properties and edible values. However, nutmeg is susceptible to fungi and mycotoxin contamination under suitable conditions during growing or post-harvest, thereby posing considerable hazards to consumers and resulting in significant economic losses. In this study, the surface fungi of nutmegs collected from producing areas and commercial markets were investigated for the first time by targeting the internal transcribed spacer 2 region using an Illumina MiSeq PE250 platform. Fungal contaminations were detected in all 13 tested samples. Aspergillus was the most prevailing fungi at the genus level with the relative abundance of 4.37%–82.81%, followed by Xerochrysium (0.36%–55.18%), Xeromyces (0.87%–86.38%), Hyphopichia (0.06%–29.14%), and Alternaria (0.03%–52.28%). Meanwhile, 108 fungal taxa were identified at the species level with six potential mycotoxin-producing fungi, such as Aspergillus fumigatus , Penicillium steckii , and Penicillium capsulatum. The differences between two groups of fungal communities were monitored. In conclusion, amplicon sequencing features a wide application prospect for fungal community analysis in spices and herbs and provides an early warning for subsequent potential mycotoxin biosynthesis. • This is the first report on fungal contamination in nutmeg using high-throughput sequencing. • Six potential mycotoxin-producing fungi were detected. • The fungal communities in two nutmeg groups exhibited statistically significant difference. [ABSTRACT FROM AUTHOR]

Background: Apoptosis Regulator BCL2 Associated X (BAX) is a pro-apoptotic gene. Apoptosis is one of the important components of immune response and immune regulation. However, there is no systematic pan-cancer analysis of BAX., Methods: Original data of this study were downloaded from TCGA databases and GTEX databases. We conducted the gene expression analysis and survival analysis of BAX in 33 types of cancer via Gene Expression Profiling Interactive Analysis (GEPIA) database. Real-time PCR and immunohistochemistry (IHC) were further performed to examine the BAX expression in cancer cells and tissues. Moreover, the relationship between BAX and immune infiltration and gene alteration was studied by the Tumor Immune Estimation Resource (TIMER) and cBioPortal tools. Protein-protein interaction analysis was performed in the STRING database. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to evaluate the enrichment analysis., Results: BAX was highly expressed in most cancers and was associated with poor prognosis in nine cancer types. In addition, BAX showed significant clinical relevance, and the mRNA expression of BAX was also strongly associated with drug sensitivity of many drugs. Furthermore, BAX may participate in proliferation and metastasis of many cancers and was associated with methylation. Importantly, BAX expression was positively correlated with most immune infiltrating cells., Conclusion: Our findings suggested that BAX can function as an oncogene and may be used as a potential predictive biomarker for prognosis and immunotherapy efficacy of human cancer, which could provide a new approach for cancer therapy.

Long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. lncRNA HOTAIR has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. And it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. We comprehensively investigated the effect of HOTAIR expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases like The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). Bioinformatics data indicated that HOTAIR was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer, especially in colorectal cancer (CRC). Subsequently, this study further clarified the utility of HOTAIR that downregulation of its expression could result in reduced proliferation and invasion of CRC cells. Mechanistically, HOTAIR upregulated the metabolic enzymes UPP1 by recruiting histone methyltransferase EZH2, thereby increasing the tumor progression. Our results highlight the essential role of HOTAIR in pan-cancer and uridine bypass, suggesting that the HOTAIR/EZH2/UPP1 axis might be a novel target for overcoming CRC. We anticipate that the role of HOTAIR in metabolism could be important in the context of CRC and even exploited for therapeutic purposes.

Objective: To develop a prediction nomogram for the risk of lung-related diseases (LRD) in construction workers., Methods: Seven hundred and fifty-two construction workers were recruited. A self- designed questionnaire was performed to collected relevant information. Chest X-ray was taken to judge builders' lung health. The potential predictors subsets of the risk of LRD were screened by the least absolute shrinkage and selection operator regression and univariate analysis, and determined by using multivariate logistic regression analysis, then were used for developing a prediction nomogram for the risk of LRD. C-index, calibration curve, receiver operating characteristic curve, decision curve analysis (DCA) and clinical impact curve analysis (CICA) were used to evaluation the identification, calibration, predictive ability and clinical effectiveness of the nomogram., Results: Five hundred and twenty-six construction workers were allocated to training group and 226 to validation group. The predictors included in the nomogram were symptoms, years of dust exposure, work in shifts and labor intensity. Our model showed good discrimination ability, with a bootstrap-corrected C index of 0.931 (95% CI = 0.906-0.956), and had well-fitted calibration curves. The area under the curve (AUC) of the nomogram were (95% CI = 0.906-0.956) and 0.945 (95% CI = 0.891-0.999) in the training and validation groups, respectively. The results of DCA and CICA indicated that the nomogram may have clinical usefulness., Conclusion: We established and validated a novel nomogram that can provide individual prediction of LRD for construction workers. This practical prediction model may help occupational physicians in decision making and design of occupational health examination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Yin, Wu, Luo, Wu, Li, Jiang, Yao, Wan, Yi and Tan.)

Background: Welding fumes are a risk factor for welder pneumoconiosis. However, there is a lack of population information on the occurrence of welding fume-induced lung cancer, and little is known about the welding fume pathogenesis., Methods: Welding fume and metal ion concentrations were assessed in a vehicle factory in Wuhan. A Cox regression model estimated lung-related disease risk in workers by independent and combined factors., Results: Workers' exposures were divided into four grades; the highest exposure was among the welders in the maintenance workshop, the highest Mn and Fe exposure was 4 grades, and the highest Cr exposure was 3 grades. Subgroup analysis found that the risk of lung-related disease was 2.17 (95% CI: 1.31-3.57, p < 0.05) in welders compared with non-welders, and the risk of pulmonary disease in male welders was 2.24 (95% CI: 1.34-3.73, p < 0.05) compared to non-welders. Smoking welders had a 2.44 (95% CI: 1.32-4.51, p < 0.01) higher incidence of lung-related diseases than non-welders. Total years of work as an independent protective factor for lung-related disease risk was 0.72 (95% CI: 0.66-0.78, p < 0.01) . As an independent risk factor, high-high and high-low exposure had a 5.39 (95% CI: 2.52-11.52, p < 0.001) and 2.17 (95% CI: 1.07-4.41, p < 0.05) higher risk for lung-related diseases, respectively., Conclusions: High welding fume exposure is a significant risk factor for lung-related disease in workers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiang, Liao, Wan, Yao, Luo, Chen, Qian, Dai, Yin, Min, Yi and Tan.)

Long non-coding RNAs (lncRNAs) are non-coding RNAs that have more than 200 nucleotides and can participate in the regulation of gene expression in various ways. An increasing number of studies have shown that the dysregulated expression of lncRNAs is related to the occurrence and progression of human cancers. LINC00665 is a novel lncRNA, which is abnormally expressed in various human cancers, such as lung cancer, breast cancer, prostate cancer, and glioma. LINC00665 functions in many biological processes of tumor cells, such as cell proliferation, migration, invasion, angiogenesis, and metabolism, and is related to the clinicopathological characteristics of cancer patients. LINC00665 can play biological functions as a ceRNA, directly binding and interacting with proteins, and as an upstream molecule regulating multiple signaling pathways. In this review, we comprehensively summarize the expression level, function, and molecular mechanisms of LINC00665 in different human cancers and emphasize that LINC00665 is a promising new diagnostic, prognostic biomarker, and therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Zhang, Chen, Bian, Li and Wang.)

Coronavirus Disease 2019 (COVID-19), which originated in Wuhan, China, has caused many healthcare workers (HCWs) to be infected. Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Although China has done a lot in strengthening the primary healthcare system, the high turnover intention is still a social problem to be reckoned with. The objective of this study is to explore the mediating effect of satisfaction between job burnout and turnover intention., Design: Cross-sectional study., Methods: A cross-sectional study was conducted to make sense of the job burnout, satisfaction and turnover intention among primary healthcare workers in central China. Structural equation modelling (SEM) was performed to study the mediating effect of satisfaction between job burnout and turnover intention with maximum likelihood estimation. The mediation effect test was carried out by using the bootstrap method., Results: SEM showed that job burnout was positively related to the turnover intention with the standard path coefficient of 0.845 (C.R.=34.055, p<0.001). The partial mediating effect of satisfaction was 0.047, making up 5.32% of the total effect. The goodness-of-fit was acceptable (Goodness of Fit Index=0.947, Comparative Fit Index=0.975, root mean square error of approximation=0.067, Non-Normed Fit Index=0.971, Incremental Fit Index=0.975). Age, education level, monthly income, hire form and night shift were also found significantly correlated with turnover intention, and no difference was found between physicians and nurses., Conclusions: The turnover intention is significantly affected by job burnout, satisfaction and demographical characteristics including age, education level, monthly income, hire form and night shift. Satisfaction can be regarded as a mediator between job burnout and turnover intention. Relative measures can be taken to promote enthusiasm and satisfaction thus decreasing the turnover rate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In this study, we explored the association between sleep quality, duration and prevalence of rheumatoid arthritis (RA) among low-income adults in rural areas of China. Methods: Face-to-face investigation were conducted in 2017, and completed questionnaires were obtained from 16,648 individuals. Sleep quality and duration were evaluated using the standard Pittsburgh Sleep Quality Index. RA was based on self-reported physician diagnosis. Logistic regression analysis and restricted cubic spline models were performed. Results: Sleep duration shorter than 7 hours was associated with increased odds of RA, with an odds ratio (OR) of 1.49 for 6-<7 hours and 1.70 for <6 hours. Poor sleep quality was associated with RA, with an OR of 1.68. The combination category of poor sleep quality and any group of sleep duration was associated with a significantly increased risk of developing RA. Combined groups of good sleep quality with short sleep duration (<7 hours) were also found to be related to prevalence of RA. There was a non-linear relationship between sleep quality, duration and the odds of RA. Conclusions: Poor sleep quality and short sleep duration may be trigger or risk factors for RA.

Objectives: To explore the association between the number of teeth and frailty among older Chinese adults using a nationally representative sample., Design: Cross-sectional analysis was carried out using the 2014 wave data from the Chinese Longitudinal Healthy Longevity Survey, which used a targeted random-sampling design., Setting: This research was conducted in communities from nearly half of the counties and cities in 22 out of 31 provinces throughout China., Participants: Of the 6934 interviewees aged ≥65 years, the final analysis included 3635 older adults who had completed the 2014 wave survey on the variables included in the study., Primary and Secondary Outcome Measures: Outcome variables included frailty, measured by the Frailty Index, and number of teeth. Covariates included demographic characteristics (ie, age, sex, co-residence, marital status, years of education and financial support), body mass index (BMI) and health behaviours (ie, smoking, drinking and exercise). A univariate logistic regression was used to test the factors associated with frailty. A multiple logistic regression model was used, using the frailty score as the dependent variable and the number of teeth together with significant covariates as the independent variables., Results: The prevalence of frailty was 27.68%. The mean number of teeth present was 9.23 (SD=10.03). The multiple logistic regression showed that older adults' demographic variables, health behaviours, BMI, tooth number and chewing pain were significantly associated with frailty. After adjusting for the covariates, older adults with fewer teeth had significantly higher odds of frailty than those with 20 or more teeth (no teeth: OR=2.07, 95% CI 1.53 to 2.80; 1 to 10 teeth: OR=1.77, 95% CI 1.31 to 2.38), except for older adults with 11 to 20 teeth (OR=1.30, 95% CI 0.93 to 1.82)., Conclusions: The presence of fewer teeth is significantly associated with frailty status among older Chinese adults. Future studies are needed to explain the specific mechanisms underlying how oral health status is associated with frailty., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Agarwood is the fragrant resin-infused wood derived from the wounded trees of Aquilaria species. It is a valuable non-timber forest product used in fragrances and as medicine. Reforestation for Aquilaria trees in combination with artificial agarwood-inducing methods serves as a way to supply agarwood and conserve of wild Aquilaria stock. However, the existing agarwood-inducing methods produce poor-quality agarwood at low yield. Our study evaluated a novel technique for producing agarwood in cultivated Aquilaria trees, called the whole-tree agarwood-inducing technique (Agar-Wit). Ten different agarwood inducers were used for comparison of Agar-Wit with three existing agarwood-inducing methods. For Aquilaria trees treated with these ten inducers, agarwood formed and spread throughout the entire tree from the transfusion point in the trunk to the roots and branches of the whole tree. Agarwood yield per tree reached 2,444.83 to 5,860.74 g, which is 4 to 28 times higher than that by the existing agarwood-inducing methods. Furthermore, this agarwood derived from Agar-Wit induction was found to have a higher quality compared with the existing methods, and similar to that of wild agarwood. This indicates Agar-Wit may have commercial potential. Induction of cultivated agarwood using this method could satisfy the significant demand for agarwood, while conserving and protecting the remaining wild Aquilaria trees.